Inflammation enhances epileptogenesis in the developing rat brain

In ?ammation enhances epileptogenesis in the developing rat brain

Stéphane Auvin a ,b ,c ,?,Andrey Mazarati a ,Don Shin a ,Raman Sankar a

a Pediatrics,David Geffen School of Medicine at UCLA,Los Angeles,CA,USA

b Pediatri

c Neurology,Robert DebréHospital,Paris,France c

INSERM U676,Paris,France

a b s t r a c t

a r t i c l e i n f o Article history:

Received 22February 2010Revised 17May 2010Accepted 11June 2010

Available online 19June 2010Keywords:

Developing brain Epileptogenesis In ?ammation Kindling LPS

Status epilepticus

In many experimental systems,proin ?ammatory stimuli exhibit proconvulsant properties.There are also accumulating data suggesting that in ?ammation may contribute to epileptogenesis in experimental models as well as in https://www.wendangku.net/doc/1617162384.html,ing two different models (Lithium-pilocarpine induced-status epilepticus (SE)and rapid kindling),we address this issue in the developing https://www.wendangku.net/doc/1617162384.html,ing P14Wistar rat pups,we showed that in ?ammation induced by LPS results,after SE,into a more severe disease in adulthood.The main histological feature was an active gliosis that was observed only when in ?ammation and SE was combined.The use of a kindling model at P14,a model where seizure progress without any neurodegeneration,permits to show that systemic in ?ammation is responsible of an enhancement of epileptogenesis.The role of in ?ammation should be further explored in immature brain to identify therapeutic targets that may be relevant to clinical practice where the association of in ?ammation and epileptic events is common.

?2010Elsevier Inc.All rights reserved.

Introduction

Febrile seizures (FS)are seizures triggered by fever that occur in 3–5%of children between the age of 6months and 5years (Berg and Shinnar,1996).In humans,retrospective analyses have considered FS,in particular prolonged FS,as a risk factor for the development of temporal lobe epilepsy (TLE)(Cendes et al.,1993;French et al.,1993).Currently,it is not proven that FS is responsible of epileptogenesis leading to TLE.FS can be a symptom of other factors that lead to the epileptogenic process.This question is particularly complex,because prospective studies in children with FS have not yet demonstrated the development of TLE.

Many experimental models of FS have used hyperthermia.However,very different physiologic mechanisms underlie fever and hyperthermia (Berg,1993).A treatment with bacterial endotoxin lipopolysaccharide (LPS)permits to induce in ?ammatory mechan-isms as with fever.In many experimental systems,proin ?ammatory stimuli exhibit proconvulsant properties (Vezzani and Granata,2005).Recently,the involvement of interleukin-1(IL-1)pathway in epileptogenesis has been suggested (Ravizza et al.,2008b ).The role of in ?ammation as a causative factor in human epileptogenesis has also been explored.An association of prolonged FS and TLE with hippocampal sclerosis with a polymorphism in the promoter of IL-1β

gene (IL-1β-511T)was reported (Kanemoto et al.,2000;Kanemoto et al.,2003).These data have been challenged by other studies (Buono et al.,2001;Heils et al.,2000).However,a recent meta-analysis suggests the link between IL-1βgene polymorphism and TLE (Kauffman et al.,2008).

In order to mimic human disease condition,it seems important to understand how in ?ammation may affect epileptogenesis in imma-ture brain.However,few data are https://www.wendangku.net/doc/1617162384.html,ing the lithium-pilocarpine model of SE at P9and P21,it has been shown that age-dependent brain in ?ammation induced by SE and vascular changes were associated with epileptogenesis,suggesting that these phenom-ena are implicated in the mechanisms underlying the occurrence of spontaneous seizures (Marcon et al.,2009).When LPS is given prior to systemic kainate injection or prior to short hyperthermic seizure,it results in a long term modi ?cation of brain excitability (Auvin et al.,2009;Heida et al.,2005).However,recent data suggest that in ?ammation in developing brain causes by itself a long lasting increase in seizure susceptibility (Galic et al.,2008).

Here,we studied the role of LPS injection on the epileptogenesis in the developing brain.For the ?rst time,we have used two models responsible of epileptogenesis in immature brain:the lithium-pilocarpine model and a rapid kindling model.We used lithium-pilocarpine in P14rats with or without LPS injections.Then we studied the rats 3months after the initial SE to examine both epileptogenesis and long term histological changes.Moreover,we used a rapid kindling model to study epileptogenesis in immature brain without any acute neuronal injury.It is the ?rst study in immature brain exploring the effect of induced-in ?ammation in models of epileptogenesis.

Neurobiology of Disease 40(2010)303–310

?Corresponding author.Service de Neurologie Pédiatrique et des Maladies Métaboliques,CHU H?pital Robert Debré,48,boulevard Sérurier,75935Paris Cedex 19,France.

E-mail address:auvin@https://www.wendangku.net/doc/1617162384.html, (S.Auvin).

Available online on ScienceDirect (https://www.wendangku.net/doc/1617162384.html,)

.0969-9961/$–see front matter ?2010Elsevier Inc.All rights reserved.doi:

10.1016/j.nbd.2010.06.004

Contents lists available at ScienceDirect

Neurobiology of Disease

j o u r n a l h o me p a g e :w w w.e l s e v i e r.c om /l oc a te /y nb d i

Materials and methods

Lithium-pilocarpine model

Animals,injection of in?ammatory factor,and induction of seizures Wistar male rat pups(Charles River Laboratories,Wilmington,MA, USA)were housed in standard laboratory conditions with controlled temperature/humidity,a12-h light/dark cycle,and free access to food and water.Studies were approved by the Animal Research Committee at the University of California,Los Angeles.

At P13,animals were injected subcutaneously with3mEq/kg lithium chloride(Sigma,St.Louis,MO,USA).After14–18h,rats received i.p.injections of either LPS(50μg/kg,E.coli serotype055:B5; Sigma),or vehicle(LiPC group).SE was induced2h later by s.c.

injection of pilocarpine(PC,Sigma)in a dose of60mg/kg at P14.Only rats that demonstrated behavioral manifestations of seizures progres-sing to forelimbs clonus during at least1h were used for further studies.

In order to investigate whether sustained in?ammation affected the long term consequences of SE,a separate group of2-week-old animals were given50μg/kg of LPS(Sigma)or vehicle2h preceding the injection of PC(60mg/kg),followed by repeated injections of 50μg/kg of LPS(3LPS+LiPC)or vehicle24and48h after the?rst LPS treatment(LPS+LiPC).A control group of three animals received lithium chloride followed by LPS and atropine,and?nally LPS24and 48h after atropine.Table1represents the four studied groups.

We use an i.p.injection of LPS2h prior the procedure as we did in our previous studies(Auvin et al.,2007,2009).We originally based this choice on experiments that demonstrate that the higher proconvulsant effect of LPS using PTZ model was2and8h after the LPS injection(Sayyah et al.,2003).Moreover,Heida et al.(2004)have used a LPS injection2.5h prior a subconvulsant dose of kainate.A recent study has also reported that the levels of cytokines in brain after i.p.injection of LPS reached the highest level after1–2h(Kwon et al.,2010).The repetitive injection of LPS after lithium-pilocarpine SE(3LPS+LiPC)was design in order to evaluate the effect of sustained in?ammation.We already reported a higher level of cell injury72h after SE at P14when LPS was given repetitively(Auvin et al.,2007).

EEG recordings(Fig.1)

Three months after the initial SE,all animals were recorded24h a day for a6-day period.Following iso?urane anesthesia administra-tion,the two leads of the EEG transmitter were operatively implanted on the dura through two drilled bilateral burr holes in the skull on each side of the cranium,(AP:4.5mm;ML:4or?4mm;V:0mm to the bregma).After surgery,the rats were transferred to the cage that was placed on top of the telemetry receiving platform(Data Sciences International,Arden Hills,MN,USA)and continuous EEG monitoring was performed after a24h period of recovery.We recorded each rat 24h a day during six consecutive days(i.e.144h of continuous recording).Stellate software(Montreal,Quebec,Canada)was used to capture the data that were then manually reviewed of?ine for epileptiform events.Video recording was combined with the EEG for each rat for duration of24h minimum.Analysis was carried out based on amplitude,frequency and time with EEG evidence of seizures.

Histology

All rats were euthanized with pentobarbital(100mg/kg,i.p.)and underwent transcardiac perfusion-?xation with saline followed by4% paraformaldehyde24h after the end of the video-EEG recording (n=11LiPC group,n=8LPS+LiPC,n=83LPS+LiPC and n=3 controls).Brains were removed,dehydrated,embedded in paraf?n, cut at8-μm-thick coronal sections,and stained with either hematox-ylin&eosin(H&E,Sigma).

To address the concern of acute neuronal injury,Fluoro-Jade B(F-JB,Histo-chem Inc.,Jefferson,AR,USA)were used.Sections for Fluoro-Jade B were deparaf?nized,rehydrated,incubated with KMnO4 followed by0.001%Fluoro-Jade B.Injured(green?uorescent)cells were examined bilaterally in the CA1,CA3,hilus and dentate gyrus in three adjacent sections in the hippocampus approximating?3.6mm posterior to bregma.Cell counting using H&E staining was also performed in the same areas of the hippocampus(Paxinos and Watson,1982).Quanti?cation of cell density was performed with a1-cm210×10-box microscopic grid.The grid of counting was placed on a well-de?ned area of the cerebral structure of interest,and counting was carried out with a microscopic enlargement of200-or400-fold de?ned for each single cerebral structure.Cell counts were performed twice on each side of three adjacent sections for each region by a single observer unaware of the animal's treatment(SA).The number of cells obtained in the12counted?elds in each cerebral structure was averaged.Neurons touching the inferior and right edge of the grid were not counted.Counts involved only neurons with cell bodies larger than10μm.Smaller cells considered as glial cells were not counted.

Immunohistochemistery

GFAP immunostaining

The slides were deparaf?nized and rehydrated.The sections were then preincubated in2%bovine serum albumin(BSA)in phosphate-buffered saline(PBS)containing0.3%Triton X-100for30min and incubated with polyclonal anti-GFAP from rabbit diluted1:200in2% BSA in PBS–Triton X-100for48h at4°C.After washing several times, tissue sections were incubated in a rabbit PAP-conjugated anti-rabbit IgG diluted1:50in PBS at room temperature for2h.The immuno-histochemical reaction was revealed by incubating the sections in a histochemical medium that contained0.06%3,3-diaminobenzidine dissolved in PBS for10min and then,in the same solution containing 1μM of3%H2O2per milliliter of DAB medium for approximately 10min.Three sections(six hippocampi)from each rat(sections every 80μm)were used to perform optical density analysis.Values of background staining were subtracted from the immunoreactive intensities of CA1area.

Table1

Design of study:studied groups in the lithium-pilocarpine models.

Two hours before pilocarpine s.c.Pilocarpine Twenty-four

hours after SE

Forty-eight

hours after SE

Control

(n=3)

50μg/kg of LPS050μg/kg of LPS50μg/kg of LPS

LiPC(n=11)Vehicle60mg/kg vehicle vehicle

LPS+LiPC

(n=8)

50μg/kg of LPS60mg/kg vehicle vehicle

3LPS+LiPC (n=8)50μg/kg of LPS60mg/kg50μg/kg of LPS50μg/kg of LPS

Table2

Results of the kindling protocol in the two studied groups.*p b0.05.

SSI+kindling

(n=12)

LPS+kindling

(n=12)

Initial ADT,mA 1.6±0.15 1.3±0.16

Initial ADD,s26.3±2.433.3±2.8

Number of stimulation to the

?rst St.4seizure

25.5±1.310.7±0.6*

Number of stage4seizure17.2±1.036.2±0.7*

Mean duration of the seizure EEG,s59.6±3.6140.8±6.2*

ADT24h after kindling,mA0.9±0.060.6±0.06*

ADD24h after kindling,s51.8±1.7162.5±7.3*

Score of seizure induced by the retest 2.7±0.2 3.7±0.2*

304S.Auvin et al./Neurobiology of Disease40(2010)303–310

NeuN-GFAP double immunostaining

The slides were deparaf?nized and rehydrated.The sections were then preincubated in2%bovine serum albumin(BSA)in phosphate-buffered saline(PBS)containing0.3%Triton X-100for30min and incubated with polyclonal anti-GFAP(Chemicon)from rabbit diluted 1:200and anti-NeuN from mouse(Chemicon)diluted1:100in2%BSA in PBS–Triton X-100for48h at4°C.After washing several times,?uorescence immunohistochemistry was performed using Alexa Fluor tagged secondary antibodies Alexa488(green)and Alexa568 (red)(Molecular Probes,Eugene,OR,USA).

Rapid kindling model

Surgery

At P13,the animals were anesthetized with Iso?urane and stereotaxically implanted with a twisted bipolar stimulating electrode (Plastics1Inc.,Roanoke,VA,USA)in the left ventral hippocampus.The coordinates with respect to Bregma were3.0-mm posterior,3.9-mm left,4.2-mm ventral.A tripolar recording electrode(Plastics1Inc.)was wrapped around skull screws using the nasal bone as the ground. Kindling procedure

The rapid kindling protocol(RKP)was adapted for immature animals(Michelson and Lothman,1991).Twenty-four hours after electrode implantation,the animals were connected to the DS8000 electrical stimulator via DSI100stimulus isolators(World Precision Instruments,Sarasota,FL,USA)and to the MP100/EEG100B acquisi-tion system(BIOPAC,Santa Barbara,CA,USA).EEG was acquired using AcqKnowledge3.8software(BIOPAC)along with simultaneous digital video.Both EEG and behavioral responses were analyzed off-line in a blinded fashion.At the beginning of the experiment,afterdischarge threshold(ADT)and afterdischarge duration(ADD)were detected by applying electrical stimuli—10-s train duration,20Hz,1-ms pulse duration,square wave monophasic stimuli,starting at0.2mA,with 0.1-mA increments,delivered every10min.

The RKP started5min after the determination of the after-discharge.Kindling consisted of60trains delivered every5min using the parameters described above using a current of100μA over the ADT.Behavioral seizures were scored:1—Motor arrest and twitching vibrissae;2—chewing,head bobbing;3—forelimb clonus;4—forelimb clonus and rearing;5—rearing and falling(Mazarati et al.,2007, 2008).Kindling progression was analyzed by calculating the number of stage4–5seizures and the duration of electrographic correlates of stage4–5convulsions.In order to examine kindling retention,24h after the end of the RKP,animals were reconnected to the stimulating recording system and afterdischarge properties were studied again. Animals were considered kindled if they showed statistically signi?cant decrease of ADT,prolongation of ADD and responded with a behavioral seizure of any stage to the threshold stimulation (Mazarati et al.,2007,2008,2009).

Design of the RKP study

All the experiments were done at room temperature22–24°C.The rat pups were randomly divided into two groups:(1)sham group receiving saline i.p.2h prior the RKP(n=12);(2)LPS treated rats receiving50μg/kg i.p.2h prior the RKP(n=12).

We also evaluate the ADT and ADD in two additional groups:(1) sham group receiving saline i.p.24h prior the AD evaluation(n=7);

(2)LPS treated rats receiving50μg/kg i.p.24h prior the AD evaluation(n=7).This last experiment was done to evaluate the role of the timing in LPS injection on the AD.We did not perform the whole kindling procedure in these groups.

Histological study

After the end of the experiments,three animals in each group were anesthetized with pentobarbital(100mg/kg),and underwent intra-cardiac perfusion with saline followed by paraformaldehyde.Brains were removed,dehydrated,embedded in paraf?n,cut at8-μm-thick coronal sections,and stained with hematoxylin&eosin(H&E,Sigma), Fluoro-Jade B and GFAP immunostaining as described above. Statistical analysis

Data are expressed as the mean±standard error of the mean (SEM).Kruskall–Wallis one-way analysis of variance(ANOVA)with post hoc Dunn's test,or Mann–Whitney rank sum test was performed. Categorical variables were analyzed by using either theχ2test or the Fisher's exact test(GraphPad Prism5Software Inc.,San Diego,CA, USA).p≤0.05was considered signi?cant.

For the study part using the lithium-pilocarpine model of SE,three types of comparison were done.The?rst analysis compared the three studied groups.A second analysis was done in order to analyze the effect of LPS.We compared all LPS-treated animals(LPS+LiPC and 3LPS+LiPC)that had SE to those that experienced SE without any LPS injection(LiPC).The third analysis was done in order to identify if the ?ndings could be related to the fact that animals have become epileptic.In this third analysis,we compared epileptic and non-epileptic animals irrespectively to their initial groups.

Results

In the lithium-pilocarpine model,LPS treated animals that had SE exhibit more severe epilepsy at adulthood(Fig.1).

Using a6-day period EEG telemetry,we found that3/11rats of the LiPC group became epileptic while5/8and4/8became epileptic in LPS+LiPC(p=0.14vs.LiPC)and3LPS+LiPC groups(p=0.3vs. LiPC),respectively(Fig.1).We observed a trend to observed more severe seizure in both LPS+LiPC and3LPS+LiPC compare to LiPC(0/ 11in LiPC vs.3/8in LPS+LiPC;p=0.06and0/11in LiPC vs.3/8in 3LPS+LiPC;p=0.06).More severe seizures(stages3–4)were only observed in groups that received LPS(LPS+LiPC and3LPS+LiPC groups)(p=0.05)(Fig.1C).The mean number of seizure per animal per day was similar among the groups(9.6Sz/day/animal in the LiPC group;6.2Sz/day/animal in the LPS+LiPC group and4.7Sz/day/ animal in the3LPS+LiPC group).None of the three controls exhibited either seizure or epileptiform activity during the recording.

Three months after the lithium-pilocarpine-SE,the number of pyramidal cell in CA-1was comparable between the groups while we found active gliosis in LPS-treated that had experienced SE.

We did not observe any difference in pyramidal cell counts in CA1 among the groups(Fig.2;upper left corner).There was also no difference in cell counts when the animals were compared according to the fact they were LPS-treated(LPS+LiPC(n=8)and3LPS+LiPC (n=8)groups)or they had SE without LPS administration(LiPC (n=11))(Fig.2;lower left corner).There was a trend of cell loss in CA-1when epileptic animals were compared to non epileptic animals (Fig.2;upper right corner).This data suggest that cell loss may be linked to the epileptic state of the animals.

All animals had a mild gliosis in CA-1but we observed a very intense reactive gliosis in CA1in all LPS-treated animals that experienced SE (Fig.3).None of the controls nor animals from LiPC group had such active gliosis(Fig.3A–B).These glial cells appeared to be more hypertrophied with thickened processes in the LPS-treated that experienced SE compared to both controls and rats from the LiPC group(Fig.3C–D).Using measurement of GFAP staining optical densities in CA-1,we found a mean density of8.7±1.2in the LiPC group,of16.6±3in the LPS+LiPC group and of14.2±1.9in the3LPS+ LiPC group.We found a signi?cant difference between LiPC vs.LPS+ LiPC(p=0.03)and LiPC vs.3LPS+LiPC(p=0.05)while there was no difference between LPS-treated group(LPS+LiPC vs.3LPS+LiPC).

Three months after the initial SE,we did not observe any Fluoro-Jade B positive cell in LiPC group while we observed Fluoro-Jade B positive cells in CA-1in two rats from LPS+LiPC group and in three

305

S.Auvin et al./Neurobiology of Disease40(2010)303–310

rats from 3LPS+LiPC group.Four of nine LPS-treated rats that developed spontaneous seizures have Fluoro-Jade B positive cells in CA-1(Fig.4D)while none of the animals that had SE showed such ?ndings.We did not observe any Fluoro-Jade B positive cell in other area.Looking at the slides from the same brains with H&E staining,we observed gliosis reaction within CA-1(Fig.4A).We also observed small acidophilic cells that were surrounded by glial reaction (Fig.4A).The double staining (NeuN-GFAP)showed that active gliosis surrounded small neuronal cells in CA-1(Fig.4B –C).

LPS enhances epileptogenesis in kindling model at P14(Table 2)Using a kindling model at P14,we found that the systemic injections of LPS 2h prior the kindling procedure have no effect on both baseline afterdischarge threshold (ADT)and afterdischarge duration (ADD).During the kindling process,the rat pups that received LPS experienced a higher number of stage 4seizure (10.7±0.6in LPS +RKP (n =12)vs.25.5±1.3in RKP (n =12);p b 0.05)and a longer mean duration of the seizure as well (140.8s±6.2in LPS +RKP vs.59.6s±3.6in RKP;p b 0.05).The enhancement of epilepto-genesis induced by LPS was sustained at the time of the retest.The ADT was lower (0.6mA ±0.06in LPS +RKP vs.0.9mA ±0.06;p b 0.05)while the ADD (162.5s±7.3vs.51.8s±1.7;p b 0.05)was increased 24h in the LPS +RKP group compared to the RKP group.In addition,the retest induced stronger seizure with a score at 3.7±0.2in LPS +RKP and at 2.7±0.2in RKP.No cell injury was observed in both groups.

When LPS was given 24h prior the AD evaluation (n =7in each group),we did not observe any difference between the groups in both ADT (2mA±0.4in saline 24h prior AD evaluation (n =7)vs.1.4mA±0.2in LPS 24h prior AD evaluation (n =7);p =0.4)and ADD (83.1±10.9saline vs.68.6±7.5LPS 24h prior;p

=0.17).

Fig.1.A:Table with the number of epileptic rats and the various types of seizures (stages 1–2,stages 3–4,re ?ex seizure)that were observed in the studied groups.B:Example of a stage 1seizure in a rat from the LiPC group.C:Example of a stage 4re ?ex seizure in a rat from the 3LPS-LiPC group.

306S.Auvin et al./Neurobiology of Disease 40(2010)303–310

We did not observe any cell injury (H&E or Fluoro-Jade B)or any signi ?cant gliosis in the different groups using the RKP.Discussion

We showed that in ?ammation enhances the severity of the disease after epileptogenesis following lithium-pilocarpine induced-SE in immature rat brain.We also observed a strong reactive gliosis three months after the initial SE in LPS-treated animals.Our previous data showed that injection of LPS at 22–24RT did not result in the increase of body temperature or increase of the duration of SE (Auvin et al.,2007);therefore the observed changes cannot be attributed to hyperthermia or to a longer duration of seizure.We also study,for the ?rst time,the effect of induced-in ?ammation using a rapid kindling model in immature brain.By using this model that does not induce acute cell injury,we observed an enhancement of epilepto-genesis by a systemic injection of LPS without any modi ?cation of baseline excitability.

It is now well established that consequences of SE in experimental models vary according to the maturity of the brain and to the different models (Haas et al.,2001;Sankar et al.,1998).In the lithium-pilocarpine model,acute cell injury pattern is different depending when SE is induced.Damage to the CA1neurons was maximal in the 2-and 3-week-old pups and decreased as a function of age (Sankar et al.,1998).We recently showed that LPS exacerbated hippocampal injury in both P7and P14rat pups (Auvin et al.,2007).Regarding the long term consequences,few animals that underwent SE at 2weeks of age developed spontaneous seizures later in life while most of the animals that underwent SE at 3or 4weeks of age exhibit spontaneous seizures (Dubéet al.,2001;Priel et al.,1996;Sankar et al.,1998).Here,we showed that the number of epileptic animals increases in LPS-treated animals suggesting that in ?ammation concomitant to SE enhance epileptogenesis.However,the number of epileptic animal did not reach the signi ?cant.We found a signi ?cant difference only for stage 3–4seizure suggesting a more severe disease in the combined LPS-treated groups.

The role of in ?ammation in epileptogenesis was ?rst suggested by the fact that in ?ammatory mediators were upregulated in both astrocytes and neurons after SE until the onset of spontaneous seizures (Ravizza et al.,2008b ).These studies had particularly highlighted the potential role of IL-1system (Ravizza et al.,2005,2008a ).It has been also suggested that IL-1βis involved in epileptogenesis using a selective inhibition of Interleukin Converting Enzyme (ICE)cleaving the biologically active form of IL-1β(

Ravizza

Fig.2.Histograms of the number (mean ±SEM)of pyramidal cell in CA-1counted using a grid.A:Pyramidal cell counts in CA-1in the three studied groups.B:Pyramidal cell counts in CA-1comparing epileptic animals versus non-epileptic animals.C:Pyramidal cell counts in CA-1comparing LPS-treated versus non-LPS-treated animals.D:Hematoxylin &eosin stained brain section taken at the level of the hippocampus representing the areas where the cell counts were performed.We did not observe any difference in pyramidal cell counts in CA1among the groups.There was also no difference in cell counts when the animals were compared according to the fact they were LPS-treated or they had SE without LPS administration.There was a trend of cell loss in CA-1when epileptic animals were compared to non epileptic animals.

307

S.Auvin et al./Neurobiology of Disease 40(2010)303–310

et al.,2008b ).In humans,a polymorphism in the promoter region of the IL-1βgene is linked to temporal lobe epilepsy (TLE)(Kanemoto et al.,2000,2003;Kauffman et al.,2008).

In immature brain,in ?ammation and microvasculature changes were observed after lithium-pilocarpine induced-SE in P21but not in P9rats.These changes were seen only in animals showing spontaneous seizures in adulthood.This study has suggested that in ?ammation becomes self-sustained and chronic only in a fraction of animals (Marcon et al.,2009).In the developing brain,it has been shown that neuroin ?ammation by itself in early development or a combination of LPS injection and a model of seizure causes a long-lasting increase in seizure susceptibility (Auvin et al.,2009;Galic et al.,2008;Heida et al.,2005).Here,we showed that combination of neuroin ?ammation and lithium-pilocarpine induced SE had aggravated epileptogenesis by a modi ?cation of the severity of the disease.In the lithium-pilocarpine model,our ?ndings may be compared to other studies that combined factors to produce a ‘double-hit injury ’(Koh et al.,2004;Scantlebury et al.,2005;Schmid et al.,1999;Setkowicz et al.,2006).The double hit hypothesis suggested that a combination of two factors is needed in immature brain to be responsible of a signi ?cant epileptogenesis.The association of hypoxia,freeze-induced cortical microgyric lesion,cortical mechanical injury or repetitive neonatal seizure with a latter prolonged seizure is responsible of the increase of SE-induced consequences.Here,the induced-neuroin ?ammation associated with lithium-pilocarpine induced-SE at P14may be considered as a double injury model.

The increase of the number of animal with epilepsy and the increase of the severity in epilepsy in our study may be related to the increase of SE-induced cell injury by in ?ammation after lithium-pilocarpine at P14(Auvin et al.,2007).Using a perinatal Hypoxia –Ischemia model to induce post-stroke epilepsy,it has been strongly suggested that a signi ?cant injury is required to induce epileptogenesis with spontane-ous recurrent seizures (Kadam et al.,2010).Looking at the cell count in CA-1in adulthood,we did not observe any difference among the groups.However,a trend was observed in the comparison of epileptic versus non-epileptic animals.This discrepancy between our results and our previous study may be due to the methods of cell count.We cannot also exclude that the process of cell injury was still ongoing because we observed Fluoro-Jade B positive cells.

The development of glial activation after experimental SE is also well known.It has been shown in several models of epilepsy after SE (Aronica et al.,2000;Immonen et al.,2008).An active astrogliosis has been also described in other models of epileptogenesis without cell degeneration such as kindling procedure (Khurgel et al.,1995).After SE onset,hippocampal glia activation,cytokine expression,and neuronal damage seem to be an age-dependent phenomena (Marcon n et al.,2009).In the hippocampus,neuronal injury occurs only when cytokines are induced in glia,and cytokine synthesis precedes the appearance of degenerating neurons.It has also been shown,in immature brain,that neuroin ?ammation itself may result in glial activation in adulthood (Galic et al.,2008).The combination of LPS and lithium-pilocarpine induced-SE may explain the observed strong active gliosis (LPS-SE and 3LPS-SE groups).A mild gliosis was observed in LPS and in SE group.Undoubtedly,the most conspicuous property of astrocytes is their morphological transformation in response to virtually any type of neural insult.This aspect of astrocytic function has been studied extensively,but its functional signi ?cance is vague in most types of CNS perturbations.Studies of tissue from patients with various forms of epilepsy and the experimental work on animals reveal that an apparent gliosis is almost always present in brain regions which exhibit epileptiforrn activity.Astrogliosis is a common feature observed in patients with mesial temporal lobe epilepsy (Eid et al.,2008).The involvement of glial cells in seizure occurrence is now well established (Angulo et al.,2004;Tian et al.,2005).Several studies showed the implication of the number and distribution of astrocytes to enhance seizure susceptibility in

a

Fig.3.GFAP-immunostaining in the hippocampus.A:CA-1of a rat from control group.B:CA-1of a rat from LiPC group at higher magni ?cation showing a moderate gliosis.C:CA-1of a rat from LPS+LiPC group at higher magni ?cation showing strong reactive gliosis.D:CA-1of a rat from 3LPS +LiPC group at higher magni ?cation showing strong reactive gliosis.Note in both C and D panel the aspect of the glial cells that are hypertrophic with thick processes.

308S.Auvin et al./Neurobiology of Disease 40(2010)303–310

number of seizure models (Oberheim et al.,2008;Somera-Molina et al.,2007).An increasing number of studies have shown that astrocytes can be signi ?cant sources of extracellular glutamate (Eid et al.,2008).Astrocytes can also synthesize and release proin ?am-matory cytokines like microglia (Dong and Benveniste,2001;Kipp et al.,2008;Vezzani et al.,2008;Wetherington et al.,2008).

Three months after the initial SE,we observed Fluoro-Jade B positive cells in CA-1.This was observed only in 4/9epileptic animals form the LPS-treated and SE groups (LPS+LiPC and 3LPS+LiPC).Several studies have shown that neuronal cell deaths are induced by the initial SE but not by the repeated spontaneous seizure that occurred after the epileptogenesis phase (Du et al.,1995;Nevander et al.,1985;Schwob et al.,1980).However,it has been described that few FJ positive stained cells may be observed 6weeks after SE in CA1,in CA-3and in the piriform cortex.This was not observed in rats 3months after they had SE (Gorter et al.,2003).The majority of cells that die as a consequence of the initial SE,degenerate in the course of the ?rst weeks after SE (Covolan and Mello,2000;Gorter et al.,2003;Ingvar et al.,1988;Poirier et al.,2000).In our study,it seems that the reactive gliosis in CA-1surround neuron and may be responsible of cell suffering or cell injury.We are currently unable to describe the evolution of such cells.Since we observed such cell only in rat that exhibit strong reactive gliosis,we should consider that the ampli ?cation of glutamate toxicity by glia might be involved (Eid et al.,2008).Using a kindling model in P14rats,we were able to study the effect of in ?ammation on epileptogenesis in the developing brain in a model where seizure progression occurs in the absence of neurodegenera-tion.We found that systemic injection of LPS enhances epileptogen-esis.The systemic injection of LPS did not result in any signi ?cant modi ?cation of the baseline excitability when LPS is given 2or 24h prior the AD evaluation.We can then exclude a facilitation of the epiletogenesis by a prior hippocampal hyperexcitability.During the kindling process,the acquisition of the kindling was easier.These effects were still observed on the afterdischarge retest.We conclude that systemic in ?ammation by LPS injection is responsible of increased epileptogenesis in immature brain.As previously described in this model,we did not observe any acute cell injury (Mazarati et al.,2007,2008,2009).The absence of signi ?cant gliosis is probably related to the short duration of this procedure.We cannot exclude the involvement of glial cells only on the absence of histological change.

In conclusion,neuroin ?ammation induced by systemic injection of LPS in immature brain is responsible for the worsening of the consequences of the lithium-pilocarpine model.Regarding the recent data on neuroin ?ammation in immature brain,we conclude that in ?ammation combine with SE should be considered as a double hit injury model.The use of a kindling model at P14permits to show that systemic in ?ammation is responsible for an enhancement of epilep-togenesis.The role of in ?ammation should be further explored

in

Fig.4.A:H&E showing damage of CA-1in a rat from LPS +LiPC group.A small cell with acidophilic cytoplasm is surrounded by a ?brillar structure.B:Double immunostaining NeuN-GFAP in CA-1area from LiPC group showing a mild gliosis within CA-1;C:Double immunostaining NeuN-GFAP in CA-1with strong gliosis in a rat from LPS+LiPC.The gliosis surrounds the neurons.Note the decrease of the size of the NeuN staining in the area of gliosis.D:Fluoro-Jade B staining in CA-1area that was observed only in LPS treated animals that exhibit spontaneous recurrent seizures.E:Representation in a stereotaxic atlas of the location of the positive Fluoro-Jade B staining.

309

S.Auvin et al./Neurobiology of Disease 40(2010)303–310

immature brain to identify therapeutic targets that may be relevant to clinical practice where the association of in?ammation and epileptic events is common.

This work was supported by NS059505,MH079933and the Epilepsy Foundation of America.

References

Angulo,M.C.,Kozlov,A.S.,Charpak,S.,Audinat,E.,2004.Glutamate released from glial cells synchronizes neuronal activity in the hippocampus.J.Neurosci.24,6920–6927. Aronica,E.,van Vliet,E.A.,Mayboroda,O.A.,Troost,D.,da Silva,F.H.,Gorter,J.A.,2000.

Upregulation of metabotropic glutamate receptor subtype mGluR3and mGluR5in reactive astrocytes in a rat model of mesial temporal lobe epilepsy.Eur.J.Neurosci.

12,2333–2344.

Auvin,S.,Shin, D.,Mazarati, A.,Nakagawa,J.,Miyamoto,J.,Sankar,R.,2007.

In?ammation exacerbates seizure-induced injury in the immature brain.Epilepsia 48(Suppl5),27–34.

Auvin,S.,Porta,N.,Nehlig,A.,Lecointe,C.,Vallee,L.,Bordet,R.,2009.In?ammation in rat pups subjected to short hyperthermic seizures enhances brain long-term excitability.Epilepsy Res.86,124–130.

Berg,A.T.,1993.Are febrile seizures provoked by a rapid rise in temperature?Am.J.Dis.

Child.147,1101–1103.

Berg,A.T.,Shinnar,S.,1996.Unprovoked seizures in children with febrile seizures: short-term outcome.Neurology47,562–568.

Buono,R.J.,Ferraro,T.N.,O'Connor,M.J.,Sperling,M.R.,Ryan,S.G.,Scattergood,T., Mulholland,N.,Gilmore,J.,Lohoff,F.W.,Berrettini,W.H.,https://www.wendangku.net/doc/1617162384.html,ck of association between an interleukin1beta(IL-1beta)gene variation and refractory temporal lobe epilepsy.Epilepsia42,782–784.

Cendes,F.,Andermann,F.,Gloor,P.,Lopes-Cendes,I.,Andermann,E.,Melanson,D., Jones-Gotman,M.,Robitaille,Y.,Evans,A.,Peters,T.,1993.Atrophy of mesial structures in patients with temporal lobe epilepsy:cause or consequence of repeated seizures?Ann.Neurol.34,795–801.

Covolan,L.,Mello,L.E.,2000.Temporal pro?le of neuronal injury following pilocarpine or kainic acid-induced status epilepticus.Epilepsy Res.39,133–152.

Dong,Y.,Benveniste,E.N.,2001.Immune function of astrocytes.Glia36,180–190. Du,F.,Eid,T.,Lothman,E.W.,Kohler,C.,Schwarcz,R.,1995.Preferential neuronal loss in layer III of the medial entorhinal cortex in rat models of temporal lobe epilepsy.J.

Neurosci.15,6301–6313.

Dubé,C.,da Silva Fernandes,M.J.,Nehlig,A.,2001.Age-dependent consequences of seizures and the development of temporal lobe epilepsy in the rat.Dev.Neurosci.

23,219–223.

Eid,T.,Williamson,A.,Lee,T.S.,Petroff,O.A.,de Lanerolle,N.C.,2008.Glutamate and astrocytes—key players in human mesial temporal lobe epilepsy?Epilepsia49 (Suppl2),42–52.

French,J.A.,Williamson,P.D.,Thadani,V.M.,Darcey,T.M.,Mattson,R.H.,Spencer,S.S., Spencer,D.D.,1993.Characteristics of medial temporal lobe epilepsy:I.Results of history and physical examination.Ann.Neurol.34,774–780.

Galic,M.A.,Riazi,K.,Heida,J.G.,Mouihate,A.,Fournier,N.M.,Spencer,S.J.,Kalynchuk,L.

E.,Teskey,G.C.,Pittman,Q.J.,2008.Postnatal in?ammation increases seizure

susceptibility in adult rats.J.Neurosci.28,6904–6913.

Gorter,J.A.,Goncalves Pereira,P.M.,van Vliet,E.A.,Aronica,E.,Lopes da Silva,F.H., Lucassen,P.J.,2003.Neuronal cell death in a rat model for mesial temporal lobe epilepsy is induced by the initial status epilepticus and not by later repeated spontaneous seizures.Epilepsia44,647–658.

Haas,K.Z.,Sperber,E.F.,Opanashuk,L.A.,Stanton,P.K.,Moshe,S.L.,2001.Resistance of immature hippocampus to morphologic and physiologic alterations following status epilepticus or kindling.Hippocampus11,615–625.

Heida,J.G.,Boisse,L.,Pittman,Q.J.,2004.Lipopolysaccharide-induced febrile convul-sions in the rat:short-term sequelae.Epilepsia45,1317–1329.

Heida,J.G.,Teskey,G.C.,Pittman,Q.J.,2005.Febrile convulsions induced by the combination of lipopolysaccharide and low-dose kainic acid enhance seizure susceptibility,not epileptogenesis,in rats.Epilepsia46,1898–1905.

Heils,A.,Haug,K.,Kunz,W.S.,Fernandez,G.,Horvath,S.,Rebstock,J.,Propping,P.,Elger,

C.E.,2000.Interleukin-1beta gene polymorphism and susceptibility to temporal

lobe epilepsy with hippocampal sclerosis.Ann.Neurol.48,948–950.

Immonen,R.J.,Kharatishvili,I.,Sierra,A.,Einula,C.,Pitkanen,A.,Grohn,O.H.,2008.

Manganese enhanced MRI detects mossy?ber sprouting rather than neurodegen-eration,gliosis or seizure-activity in the epileptic rat hippocampus.Neuroimage40, 1718–1730.

Ingvar,M.,Morgan,P.F.,Auer,R.N.,1988.The nature and timing of excitotoxic neuronal necrosis in the cerebral cortex,hippocampus and thalamus due to?urothyl-induced status epilepticus.Acta Neuropathol.75,362–369.

Kadam,S.D.,White,A.M.,Staley,K.J.,Dudek,F.E.,2010.Continuous electroencephalo-graphic monitoring with radio-telemetry in a rat model of perinatal hypoxia–ischemia reveals progressive post-stroke epilepsy.J.Neurosci.30,404–415. Kanemoto,K.,Kawasaki,J.,Miyamoto,T.,Obayashi,H.,Nishimura,M.,2000.Interleukin (IL)1beta,IL-1alpha,and IL-1receptor antagonist gene polymorphisms in patients with temporal lobe epilepsy.Ann.Neurol.47,571–574.

Kanemoto,K.,Kawasaki,J.,Yuasa,S.,Kumaki,T.,Tomohiro,O.,Kaji,R.,Nishimura,M., 2003.Increased frequency of interleukin-1beta-511T allele in patients with temporal lobe epilepsy,hippocampal sclerosis,and prolonged febrile convulsion.

Epilepsia44,796–799.Kauffman,M.A.,Moron,D.G.,Consalvo,D.,Bello,R.,Kochen,S.,2008.Association study between interleukin1beta gene and epileptic disorders:a HuGe review and meta-analysis.Genet.Med.10,83–88.

Khurgel,M.,Switzer III,R.C.,Teskey,G.C.,Spiller,A.E.,Racine,R.J.,Ivy,G.O.,1995.

Activation of astrocytes during epileptogenesis in the absence of neuronal degeneration.Neurobiol.Dis.2,23–35.

Kipp,M.,Norkute,A.,Johann,S.,Lorenz,L.,Braun,A.,Hieble,A.,Gingele,S.,Pott,F., Richter,J.,Beyer,C.,2008.Brain-region-speci?c astroglial responses in vitro after LPS exposure.J.Mol.Neurosci.35,235–243.

Koh,S.,Tibayan,F.D.,Simpson,J.N.,Jensen,F.E.,2004.NBQX or topiramate treatment after perinatal hypoxia-induced seizures prevents later increases in seizure-induced neuronal injury.Epilepsia45,569–575.

Kwon,M.S.,Seo,Y.J.,Choi,S.M.,Won,M.H.,Lee,J.K.,Park,S.H.,Jung,J.S.,Sim,Y.B.,Suh,H.

W.,2010.The time-dependent effect of lipopolysaccharide on kainic acid-induced neuronal death in hippocampal CA3region:possible involvement of cytokines via glucocorticoid.Neuroscience165,1333–1344.

Marcon,J.,Gagliardi,B.,Balosso,S.,Maroso,M.,Noe,F.,Morin,M.,Lerner-Natoli,M., Vezzani,A.,Ravizza,T.,2009.Age-dependent vascular changes induced by status epilepticus in rat forebrain:implications for epileptogenesis.Neurobiol.Dis.34, 121–132.

Mazarati,A.,Shin,D.,Auvin,S.,Sankar,R.,2007.Age-dependent effects of topiramate on the acquisition and the retention of rapid kindling.Epilepsia48,765–773. Mazarati, A.,Wu,J.,Shin, D.,Kwon,Y.S.,Sankar,R.,2008.Antiepileptogenic and antiictogenic effects of retigabine under conditions of rapid kindling:an ontogenic study.Epilepsia49,1777–1786.

Mazarati,A.,Shin,D.,Sankar,R.,2009.Bumetanide inhibits rapid kindling in neonatal rats.Epilepsia50,2117–2122.

Michelson,H.B.,Lothman,E.W.,1991.An ontogenetic study of kindling using rapidly recurring hippocampal seizures.Brain Res.Dev.Brain Res.61,79–85. Nevander,G.,Ingvar,M.,Auer,R.,Siesjo, B.K.,1985.Status epilepticus in well-oxygenated rats causes neuronal necrosis.Ann.Neurol.18,281–290. Oberheim,N.A.,Tian,G.F.,Han,X.,Peng,W.,Takano,T.,Ransom,B.,Nedergaard,M., 2008.Loss of astrocytic domain organization in the epileptic brain.J.Neurosci.28, 3264–3276.

Paxinos,G.,Watson,C.,1982.The Rat Brain in Stereotaxic Coordinates.Academic, Sydney.

Poirier,J.L.,Capek,R.,De,K.Y.,2000.Differential progression of Dark Neuron and Fluoro-Jade labelling in the rat hippocampus following pilocarpine-induced status epilepticus.Neuroscience97,59–68.

Priel,M.R.,dos Santos,N.F.,Cavalheiro, E.A.,1996.Developmental aspects of the pilocarpine model of epilepsy.Epilepsy Res.26,115–121.

Ravizza,T.,Rizzi,M.,Perego,C.,Richichi,C.,Veliskova,J.,Moshe,S.L.,De Simoni,M.G., Vezzani,A.,2005.In?ammatory response and glia activation in developing rat hippocampus after status epilepticus.Epilepsia46(Suppl5),113–117. Ravizza,T.,Gagliardi,B.,Noe,F.,Boer,K.,Aronica,E.,Vezzani,A.,2008a.Innate and adaptive immunity during epileptogenesis and spontaneous seizures:evidence from experimental models and human temporal lobe epilepsy.Neurobiol.Dis.29, 41–49.

Ravizza,T.,Noe,F.,Zardoni,D.,Vaghi,V.,Sifringer,M.,Vezzani,A.,2008b.Interleukin converting enzyme inhibition impairs kindling epileptogenesis in rats by blocking astrocytic IL-1beta production.Neurobiol.Dis.31,327–333.

Sankar,R.,Shin,D.H.,Liu,H.,Mazarati,A.,Pereira,d.,V.,Wasterlain,C.G.,1998.Patterns of status epilepticus-induced neuronal injury during development and long-term consequences.J.Neurosci.18,8382–8393.

Sayyah,M.,Javad-Pour,M.,Ghazi-Khansari,M.,2003.The bacterial endotoxin lipopolysaccharide enhances seizure susceptibility in mice:involvement of proin?ammatory factors:nitric oxide and prostaglandins.Neuroscience122, 1073–1080.

Scantlebury,M.H.,Gibbs,S.A.,Foadjo,B.,Lema,P.,Psarropoulou,C.,Carmant,L.,2005.

Febrile seizures in the predisposed brain:a new model of temporal lobe epilepsy.

Ann.Neurol.58,41–49.

Schmid,R.,Tandon,P.,Stafstrom,C.E.,Holmes,G.L.,1999.Effects of neonatal seizures on subsequent seizure-induced brain injury.Neurology53,1754–1761.

Schwob,J.E.,Fuller,T.,Price,J.L.,Olney,J.W.,1980.Widespread patterns of neuronal damage following systemic or intracerebral injections of kainic acid:a histological study.Neuroscience5,991–1014.

Setkowicz,Z.,Nowak, B.,Janeczko,K.,2006.Neocortical injuries at different developmental stages determine different susceptibility to seizures induced in adulthood.Epilepsy Res.68,255–263.

Somera-Molina,K.C.,Robin,B.,Somera,C.A.,Anderson,C.,Stine,C.,Koh,S.,Behanna,H.

A.,Van Eldik,L.J.,Watterson,D.M.,Wainwright,M.S.,2007.Glial activation links

early-life seizures and long-term neurologic dysfunction:evidence using a small molecule inhibitor of proin?ammatory cytokine upregulation.Epilepsia48, 1785–1800.

Tian,G.F.,Azmi,H.,Takano,T.,Xu,Q.,Peng,W.,Lin,J.,Oberheim,N.,Lou,N.,Wang,X., Zielke,H.R.,Kang,J.,Nedergaard,M.,2005.An astrocytic basis of epilepsy.Nat.Med.

11,973–981.

Vezzani,A.,Granata,T.,2005.Brain in?ammation in epilepsy:experimental and clinical evidence.Epilepsia46,1724–1743.

Vezzani,A.,Ravizza,T.,Balosso,S.,Aronica,E.,2008.Glia as a source of cytokines: implications for neuronal excitability and survival.Epilepsia49(Suppl2), 24–32.

Wetherington,J.,Serrano,G.,Dingledine,R.,2008.Astrocytes in the epileptic brain.

Neuron58,168–178.

310S.Auvin et al./Neurobiology of Disease40(2010)303–310

药理学名词解释

1.1.01适应(adaptation) 1.1.02损伤(injury) 1.1.03萎缩(atrophy) 1.1.04肥大(hypertrophy) 1.1.05假性肥大(pseudohypertrophy) 1.1.06增生(hyperplasia) 1.1.07化生(metaplasia) 1.1.08鳞状上皮化生(squamous metaplasia) 1.1.09肠上皮化生(intestinal metaplasia) 1.1.10心身疾病(psychosomatic disease) 1.1.11医源性疾病(iatrogenic disease) 1.1.12变性(degeneration) 1.1.13细胞水肿(cellular swelling) 1.1.14脂肪变性(fatty degeneration or fatty change) 1.1.15虎斑心(tigroid heart) 1.1.16心肌脂肪浸润 (myocardial fatty infiltration) 1.1.17透明变性 (hyaline degeneration) 1.1.18淀粉样变性 (amyloid degeneration) 1.1.19黏液变性 (mucoid degeneration) 1.1.20含铁血黄素 (hemosiderin) 1.1.21心衰细胞(heart failure cell) 1.1.22脂褐素 (lipofuscin) 1.1.23病理性钙化 (pathologic calcification) 1.1.24营养不良性钙 化(dystrophic calcification) 1.1.25迁徙性钙化 (metastatic calcification) 1.1.26细胞死亡(cell death) 1.1.27坏死(necrosis) 1.1.28凝固性坏死 (coagulative necrosis) 1.1.29干酪样坏死 (caseous necrosis) 1.1.30坏疽(gangrene) 1.1.31液化性坏死 (liquefactive necrosis) 1.1.32纤维蛋白样坏 死(fibrinoid necrosis) 1.1.33糜烂(erosion) 1.1.34溃疡(ulcer) 1.1.35窦(sinus) 1.1.36瘘(fistula) 1.1.37空洞(cavity) 1.1.38机化 (organization) 1.1.39包裹 (encapsulation) 1.1.40凋亡(apoptosis) 1.1.41凋亡小体 (apoptotic body) 一、名词解释（此处仅列出答案要点） 1.1.01①细胞、组织或器官；②耐受刺激作用；③存活的过程；④形态：萎缩、肥大、增生、化生。 1.1.02①细胞和组织；②不能耐受有害因子刺激；③结构改变；④形态：变性或细胞死亡。 1.1.03①发育正常；②细胞、组织或器官体积缩小；③实质细胞体积缩小和或数量减少；④间质增生。 1.1.04①实质细胞的细胞器增多；②实质细胞、组织器官体积增大。 1.1.05①实质细胞体积缩小和或数量减少；②纤维或脂肪组织大量增生；③组织或器官体积增大。 1.1.06①实质细胞增多；②组织、器官体积增大。 1.1.07①一种分化成熟的细胞；②刺激因素作用；③转化为另一种分化成熟细胞的过程；④发生于同源性细胞；⑤未分化细胞向另一种分化。 1.1.08①非鳞状上皮；②转化为鳞状上皮；③常见于气管、支气管、子宫颈等处。 1.1.09①炎症或其他因素刺激；②胃黏膜或胃腺上皮；③转化为肠上皮；④常见于慢性萎缩性胃炎。 1.1.10①思想、情感障碍；②细胞损伤；③器质性疾病。

病理学名词解释

。 abscess脓肿acidophilic body 嗜酸性小体acute inflammation急性炎症acute nephritic syndrome 急性肾炎综合症adenocarcinorma腺癌adenoma腺瘤 air embolism气体栓塞alteration变质amoebiasis 阿米巴病 amruotie fluia embolism羊水栓塞anemic infarct贫血性梗死angina pectoris心绞痛 apoptosis凋亡arterial hyperemia动脉性充血arteriolosclerosis细动脉硬化症 aschoff body阿少夫小体atherosclerosis动脉粥样硬化atrophy萎缩atypia异型性 bacillary dysentery菌痢bacteremia菌血症ballooning degeneration气球样变性 bronchiectasis支气管扩张bridging necrosis桥接坏死carcinoid类癌 carcinoma in situ原位癌carcinoma of breast乳腺癌carcinoma of esophegus食道癌carcinoma of stomach胃癌carcinoma of thyroid甲状腺癌casepis necrosis干酪性坏死 cervical carcinoma子宫颈癌chemotaxis趋化作用choriocarcinoma绒癌chronic bronchitis慢性支气管炎chronic cor pulmonale慢性肺源性心脏病 chronic granulomatous inflammation慢性肉芽肿性炎 chronic inflammation慢性炎症chronic peptic ucler慢性消化性溃疡coagulative necrosis凝固 性坏死concentric hypertophy向心性肥大 congestion淤血cor villosum绒毛心coronary heart disease冠心病 decompression sickness 减压病degeneration变性 dysplasia非典型增生 edema水肿embolic abscess栓塞性脓肿 embolism栓塞embolus栓 子 emigration游出epidemic enecphalitis乙型脑炎 ethiology病因学exudation 渗出 fat embolism脂肪栓塞fatty degeneration脂肪变性 fibrinous inflammation纤维 素性炎 fistula瘘管gangrene坏疽 gastritis胃炎 glomerulonephritis肾小球 肾炎 goodpasture syndrome肺 出血肾炎综合征 granulation tissue肉芽组 织 healing first intention一期 愈合healing second intention二期愈合 heart failure cell心衰细胞 hemorrhage出血 hemorrhagic infarct出血性 梗死 hodgkin disease霍奇金病 hyaline thrombus透明血栓 hydatidiform mole葡萄胎 hydropic degeneration水 变性hyperemia充血 hyperplasia增生 hypertension高血压 hypertrophy肥大infarction 梗死inflammation炎症 inflammatory mediator炎 症介质 invasive mole侵蚀性葡萄 胎karyolysis核溶解 karyorrhexis核碎裂keratin pearl角化珠 lipoid nephrosis慢性肾炎 lipoma脂肪瘤liquefactive necrosis液化性坏死 liver cirrhosis肝硬化lobar pneumonia大叶性肺炎 lobular pneumonia小叶性 肺炎 malignant lymphoma恶性 淋巴癌medullary carcinoma髓样癌 meningitis脑膜炎 metaplasia 化生 metastasis转移mixed thrombus混合血栓 molecular pathology分子 病理学myocardial infarction心肌梗死 myxedema粘液性水肿 nasopharyngeal carcinoma鼻咽癌necrosis 坏死 nephritic syndrome肾病综 合症nontoxic goiter单纯性 甲状腺肿nutmeg liver槟榔 肝 oncogene癌基因 organization机化 osteosarcoma骨肉瘤 pale thrombus白色血栓 papilloma乳头状瘤 pathogenesis发病学 pathological changes病变 pathology病理学 phlegmonous inflammation蜂窝织炎 piecemeal necrosis碎片状 坏死pipe stem cirrhosis干 线型肝硬化 pleomorphism多形性 polyp息肉portal cirrhosis 门脉性肝硬化 post necrotic cirrhosis坏死 后肝硬化primary carcinoma of liver原发性 肝癌 primary complex原发综合 症proliferation增生 pulmonary emphysema肺 气肿 pyelonephritis肾盂肾炎 pyemia脓毒血症pyknosis

分子生物学 名词解释

名词解释 1. 基因（gene）： 2. 结构基因（structural gene）： 3. 断裂基因（split gene）： 4. 外显子（exon）: 5. 内含子（intron）: 6. 多顺反子RNA（polycistronic/multicistronic RNA）: 7. 单顺反子RNA（monocistronic RNA）: 8. 核不均一RNA（heterogeneous nuclear RNA, hnRNA）: 9. 开放阅读框（open reading frame, ORF）: 10. 密码子（codon）: 11. 反密码子（anticodon）: 12. 顺式作用元件（cis-acting element）: 13. 启动子（promoter）: 14. 增强子（enhancer）: 15. 核酶（ribozyme） 16. 核内小分子RNA（small nuclear RNA, snRNA） 17. 信号识别颗粒（signal recognition particle, SRP） 18. 上游启动子元件（upstream promoter element） 19. 同义突变（same sense mutation） 20. 错义突变（missense mutation） 21. 无义突变（nonsense mutation） 22. 移码突变（frame-shifting mutation） 23. 转换（transition） 24. 颠换（transversion） （三）简答题 1. 顺式作用元件如何发挥转录调控作用？ 2. 比较原核细胞和真核细胞mRNA的异同。 3. 说明tRNA分子的结构特点及其与功能的关系。 4. 如何认识和利用核酶？ 5. 若某一基因的外显子发生一处颠换，对该基因表达产物的结构和功能有什么影响？ 6. 举例说明基因突变如何导致疾病。 （四）论述题 1. 真核生物基因中的非编码序列有何意义？ 2. 比较一般的真核生物基因与其转录初级产物、转录成熟产物的异同之处。 3. 真核生物的基因发生突变可能产生哪些效应？ （二）名词解释 1.基因组（genome） 2. 质粒（plasmid） 3.内含子（intron） 4.外显子（exon） 5.断裂基因（split gene） 6.假基因（pseudogene） 7.单顺反子RNA（monocistronic RNA）

医学免疫学名解英文

免疫 Immune response: the response made by the host to defend itself against the introduction of foreign substances. Antigen: An antigen is any agent capable of binding specifically to components of immune system, such as BCR and soluble antibodies Immunogen - A substance that induces a specific immune response. (All immunogens are antigens, but not all antigens are immunogens) Antigenicity: The ability of a compound to bind with antibodies or cells of the immune system. This binding is highly specific. Immunogenicity Immunogenicity is the ability of a particular substance, such as an antigen or epitope, to provoke a specific immune response in the body of a human or animal. Hapten半抗原：A hapten is a small molecule which can elicit an immune response only when attached to a large carrier such as a protein; the carrier may be one which also does not elicit an immune response by itself. Epitope Epitope is the portion of the antigen that binds specifically with the binding site of an antibody or a receptor on a lymphocyte. TI-Ag Thymus -independent antigens are antigens which can directly stimulate the B cells to produce antibody without the requirement for T cell help in general. TD-Ag Thymus -dependent antigens are those that do not directly stimulate the production of antibody without the help of T cells Super antigen An antigen which polyclonally activates some subtypes of the T cells (up to 20%). Adjuvants:A substance that when mixed with an immunogen, enhances the immune response against the immunogen. Immunoglobulin The Immunoglobulins are globulin which function as antibodies or similar to antibodies in chemical structure. Complementarity determining region (CDR)互补决定区：A complementarity determining

牙周专业英语

牙周专业英语常用词汇

牙周专业英语课文 CLINICAL FEATURE OF CHRONIC PERIODONTAL DISEASE Chronic gingivitis The manifestations of gingival inflammation vary considerably between individuals and from one part of the mouth to another. This variation reflects the aetiological factors at work and the tissue response to these factors. This response is essentially a mixture of inflammation and fibrous tissue repair. When the former predominates, signs and symptoms are more obvious; when the fibrous tissue component predominates, clinical manifestations can be much more subtle and recognized only by careful examination. In making a diagnosis it is important to keep in mind the appearance of health, departures from which may indicate disease. Clinical features are: l . Altered gingival appearance. 2. Gingival bleeding. 3. Discomfort and pain 4. Unpleasant taste

名词解释

名词解释 1病理学（pathology）：研究疾病的病因、发病机制、病理变化、结局和转归的医学基础学科。 2适应（adaptation）：细胞和其构成的组织、器官，对于内外环境中各种有害因子和刺激作用而产生的非损伤性应答反应 3萎缩（atrophy）：已发育正常的细胞、组织或器官的体积缩小 4肥大（hypertrophy）：由于功能增加，合成代谢旺盛，使细胞、组织或器官体积增大 5增生（hyperplasia）：组织或器官内实质细胞数目增多 6化生（metaplasia）：一种分化成熟的细胞类型被另一种分化成熟的细胞类型所取代的过程7损伤（injury）：当机体内外环境改变超过组织和细胞的适应能力后，可引起受损细胞和细胞间质发生物质代谢，组织化学，超微结构可至光镜和肉眼可见的异常变化 8细胞可逆性损伤（reversible injury）：旧称变性（degeneration），细胞或细胞间质受损伤后，由于代谢障碍，使细胞内或细胞间质内出现异常物质或正常物质异常蓄积的现象 细胞水肿（cellular swelling）：旧称水变性（hydropic degeneration），细胞内钠离子和水的过多积聚 脂肪变（fatty change/steatosis）：中性脂肪特别是甘油三酯蓄积于非脂肪细胞的细胞质中玻璃样变（hyalinization）或透明变性（hyaline degeneration）:细胞内或间质中出现半透明状蛋白质蓄积 淀粉样变（amyloid change）：细胞间质出现淀粉样蛋白质-粘多糖复合物沉淀 黏液样变（mucoid degerenation）：细胞间质内粘多糖和蛋白质的蓄积 病理性色素沉着（pathologic pigmentation）：有色物质在细胞内、外的异常蓄积 病理性钙化（pathologic calcification）：骨和牙齿之外的组织中固态钙盐沉积 9*凝固性坏死（coagulative necrosis）：蛋白质变性凝固且溶酶体酶水解作用较弱时，坏死区呈灰黄、干燥、质实状态，称为凝固性坏死 10液化性坏死（liquefactive necrosis）：由于坏死组织中可凝固的蛋白质少，或坏死细胞自身及浸润的中性粒细胞等释放大量水解酶，或组织富含水分和磷脂，则细胞组织坏死后易发生溶解液化，称为液化性坏死 11纤维素样坏死（fibrinoid necrosis）：是结缔组织及小血管壁常见的坏死形式。病变部位形成细丝状、颗粒状或小条块状无结构物质，由于其与纤维素染色性质相似，故名纤维素样坏死 12*坏疽（gangrene）：局部组织大块坏死并继发腐败菌感染。干性（dry）坏疽常见于动脉阻塞但静脉回流尚通畅的四肢末端，湿性（moist）坏疽多发生于与外界相通的内脏，也发生于动脉阻塞及静脉回流受阻的肢体，气性（gas）坏疽系深达肌肉的开放性创伤，合并产气荚膜杆菌等厌氧菌感染 13修复（repair）：损伤造成机体部分细胞和组织丧失后，机体对所形成缺损进行修补恢复的过程。由损伤周围的同种细胞来修复，称为再生（regeneration） 14*肉芽组织（granulation tissue）：由新生薄壁的毛细血管以及增生的纤维母细胞构成，并伴有炎细胞的浸润，肉眼观为鲜红色、颗粒状、柔软湿润，形似鲜嫩的肉芽，故名 15瘢痕（scar）组织：是指肉芽组织经改建成熟形成的纤维结缔组织。由大量平行或交错分布的胶原纤维束组成 16动脉性充血（arterial hyperemia）：器官或组织因动脉输入血量的增多而发生的充血17淤血（congestion）: 器官以及局部组织静脉血回流受阻，以致血液淤积在静脉和毛细血管内

慢性炎症与结直肠癌微环境

Advances in Clinical Medicine临床医学进展, 2015, 5(4), 199-206 Published Online December 2015 in Hans. https://www.wendangku.net/doc/1617162384.html,/journal/acm https://www.wendangku.net/doc/1617162384.html,/10.12677/acm.2015.54032 Chronic Inflammation and Colorectal Cancer Microenvironment Wenrui Lian1, Dongmei Ma2, Peide Dong1* 1Department of General Surgery, Affiliated Hospital, Inner Mongolia Medical University, Hohhot Inner Mongolia 2Department of Vasculocardiology, Zibo Coal Central Hospital, Zibo Shandong Received: Nov. 25th, 2015; accepted: Dec. 14th, 2015; published: Dec. 18th, 2015 Copyright ? 2015 by authors and Hans Publishers Inc. This work is licensed under the Creative Commons Attribution International License (CC BY). https://www.wendangku.net/doc/1617162384.html,/licenses/by/4.0/ Abstract Inflammation is a very common and important basic pathological process, mainly by the pathogen, physical or chemical damage caused. The course of the disease is divided into two broad catego-ries: acute inflammation and chronic inflammation. The main function of acute inflammation is to eliminate infection of the organization, to maintain the physiological balance in the body. Chronic inflammation can cause cell malignant transformation, resulting in the occurrence of cancer. The existing research results show that many inflammatory cytokines play an important role in the process of development and cancer initiation, such as IL-6, TNF-alpha and TGF-beta. In this review, we argue that these inflammatory factors have played a very important role in the process of in-duced cancer. At the same time, we analyzed its effect of the process of the inflammatory cytokines in proctitis related colorectal cancer. Keywords Chronic Inflammation, Colorectal Cancer, Inflammatory Cytokines, IL-6, TNF-α, TGF-β 慢性炎症与结直肠癌微环境 廉文瑞1，马冬梅2，董培德1* 1内蒙古医科大学附属医院普通外科，内蒙古呼和浩特 2淄矿集团中心医院血管内科，山东淄博 *通讯作者。

免疫学名词解释英

免疫名词解释历年题 1. Recirculation of lymphocytes(淋巴细胞再循环)It means the continuo us movement of lymphocytes across the sites through out blood and lym phatic vessels, and it is critical for the initiation and effector phases of i mmune response. 2. hapten(半抗原) antigen which can combine with the corresponding Ab or sensitized T lymphocyte but can not evoke the immune response independently. 3. TD-Ag(thymus dependent Ag) Ag stimulates B cells to produce Ab with the help of T cells and macrophage. 4. TI-Ag(thymus independent Ag)Ag stimulates B cells to produce Ab without the help of T cells and macrophage. 5. heterophile Ag(异嗜性抗原)common antigens shared by different sp ecies and play an important role in immunopathology and diagnosis. 6. HVR(hypervariable region)超变区Most of sequence differences am ong antibodies are confined to three short stretches in the V regions of heavy and light chains are called HVR 7. CDR(complementary determinant region)互补决定区The sequences of the antibodies form an antigen binding surface that is complementary to the three dimensional structure of the bound antigen It is also called complementary determinant regions. 8. idiotype (独特型) Igs produced by each B cells clone possessing unique structure respectively in HVR or CDR, the unique structure is call ed idiotype of Ig. 9. monoclonal Ab (mAb 单克隆抗体) It is prepared by hybridoma tec hnique. Immunized spleen cells (B cells) fuse with myeloma cells and for m hybridoma with property of proliferating Ab 10. conformational determinants 构象决定簇They are composed of amin o acid residues are not in a sequence but become special juxtaposed in

炎症不同种类(英文)different inflammation types

Histological types 1 Alterative inflammation (1) Alterative changes are the most obvious, exudative and proliferative changes are slighter. (2) Commonly seen in parenchyma organs (3) Causes: Virus, toxin, chemical poison, etc. (4) e.g: fulminant hepatitis, type B epidemic encephalitis, poliomyelitis, caseous pneumonia, etc. 2 Exudative inflammation Excess of a particular component of the inflammatory exudates imparts distinctive features. (1) Serous inflammation ①Watery, low protein content, derived from blood or serosal lining cells. ②Commonly seen in: Mucous membrane, serosa, lung, loose connective tissue, skin. ③Examples: Blister formation following burning, the pleural effusion associated with tuberculosis, common cold, etc. (2) Fibrinous inflammation ①Much fibrin due to coagulation of large fibrinogen outpouring. ②Causes: Shigella Streptococcus peneumoniae Corynebacterium diphtheriae Hg poison Uremia ③Commonly seen in a. Serosa b. Mucous membrane: Pseudo-membrane c. Lung ④Examples: Rheumatic, pericarditis, dysentery, diphtheriae, lobular peneumonir, etc. (3) Suppurative inflammation ①Definition: Much exudate with lots of neutrophils and liquefied nerotic tissue (pus) occurs. Pus composed of: dead and dying neutrophils, liquefied tissue, pyogenic organisms. ②Causes: staphylolcocci, pneumococci, gonococci, gram-negative rods, and some nonhemolytic streptococci. ③Types: a. Abscess: a localised collection of pus in an organ or tissue. Abscess could formation: Ulcer: localized defect in an epithelial surface due to necrosis. Sinus: an abnormal tract leading from a cavity to the surface. Fistula: a tract open at both ends, through which abnormal communicaton between two surface is established. b. Phlegmonous inflammation Definition: wide-spread purulent inflammation in loose tissue, and appendix Causes: hemolytic streptococci c. Surface purulent inflammation and Empyema

病理名词解释

1、病理学（pathology）：是用自然科学的方法，研究疾病的病因、发病机制、形态结构、功能和代谢等方面的改变，揭示疾病的发生、发展规律，从而阐明疾病本质的医学科学。 2、尸体剖检（autopsy）：简称尸检。指机体死亡后，以明确死亡原因为主要目的，对尸体进行系统的剖检，并按尸检程序广泛多处取材，最后作出诊断，一般不受时间上的限制。 3、活体组织检查（biopsy）：简称活检。是利用各种方法在活体病变处获取小块病变组织，以快速诊断和指导治疗为目的。 4、细胞学检查（cytology）：又称脱落细胞学。是利用能与细胞内外固有的化学成分进行特异性结合的显色试剂，显示细胞内外某些化学成分的变化。 5、适应（adaptation）：当环境改变时，机体的细胞、组织或器官通过自身的代谢、功能和结构的相应改变，以避免环境改变所引起的损伤，这个过程称为适应。 6、☉萎缩（atrophy）：发育正常的细胞、组织或器官的体积缩小。 肥大（hypertrophy）：细胞、组织或器官体积的增大。 7、☉增生（hyperplasia）：由于实质细胞数量增多而形成的组织、器官的体积增大。 8、化生（metaplasia）：为了适应环境变化，一种已分化组织转变为另一种分化组织的过程。 9、老化（aging）：当机体发育成熟后，伴随年龄的增长，全身器官的细胞功能逐渐减退且结构发生一系列退行性改变并趋向死亡，这一过程称为老化。 10、变性（degeneration）：是指细胞或间质内出现异常物质或正常物质的量显著增多，并伴有不同程度的功能障碍。 11、水变性：当缺氧、毒性物质损及线粒体内A TP产生时，细胞膜上的钠泵功能降低，使细胞膜对电解质的主动运输功能发生障碍，导致细胞内水分增多，形成细胞肿胀，严重时为水变性。 12、脂肪变性（fatty degeneration）：又称脂肪变（fatty change）。指除脂肪细胞以外的实质细胞中出现脂滴或脂滴明显增多。 13、脂肪浸润：是器官组织间质的改变，指间质中脂肪组织异常或过度积聚。 14、玻璃样变性(hyaline degeneration)：又称透明变性，是指在细胞内或间质中，出现均匀、半透明的玻璃样物质，在HE染色切片中呈均质性红染。 15、☉坏死（necrosis）：是指各种原因导致活体内范围不等的局部细胞、组织的死亡。 16、凋亡（apoptosis）：一般指机体细胞在发育过程中或在某些因素作用下，通过细胞内基因及其产物的调控而发生的一种程序性细胞死亡。 17、凝固性坏死（coagulative necrosis）：坏死组织因为失水变干、蛋白质凝固，而变为灰白色或黄白色比较干燥结实的凝固体。 18、液化性坏死（liquefactive necrosis）：有些组织坏死后被酶分解成液体状态，并可形成坏死囊腔，称为液化性坏死。 19、干酪样坏死（caseous necrosis）：主要见于由结核杆菌引起的坏死，是凝固性坏死的一种特殊类型。 20、脂肪坏死（fat necrosis）：分为溶解性和外伤性两种。 纤维素样坏死（fibrinoid necrosis）：是发生在间质、胶原纤维和小血管壁的一种坏死。21、☆坏疽（gangrene）：组织坏死后因继发腐败菌的感染和其他因素的影响而呈现黑色、暗绿色等特殊形态改变，称为坏疽。 22、糜烂（erosion）：皮肤、粘膜处的浅表性坏死性缺损。 23、☉溃疡（ulcer）：皮肤、粘膜、血管内表面的凹陷性缺损。 24、窦道（sinus）：坏死形成的开口于表面的深在性盲管。 25、瘘管（fistula）：两端开口的通道性坏死性缺损。 26、☉空洞（cavity）：坏死物液化后经相应的自然管道排出后留下的空腔。

病理学名词解释

病理学(pathology)是研究疾病发生，发展和转化规律的一门医学基础学科。其目的是认识和掌握疾病的本质和发生发展的规律，从而为防治疾病提供必要的理论基础和实践依据。 病因学(etiology)研究疾病的病因、发生条件的一门科学。 发病学（pathogenesis）病因作用下疾病发生发展的过程。 病变（pathological changes）机体在疾病过程中形态结构，功能，代谢的变化。 超微病理学(ultrastructral pathology)由于电子显微镜问世和超薄切片技术建立，病理研究遂由组织细胞水平推进至亚细胞水平，进而研讨疾病的发生与发展规律，逐步形成了超微结构病理学。 分子病理学(molecular pathology)①病理学与分子生物学、细胞生物学和细胞化学的结合；②分子水平上研究疾病发生的机制。 核浓缩（pyknosis）特征是核皱缩浓聚，嗜碱性增强。核体积缩小深染。 核碎裂（karyorrhexis）表现为核膜破裂，核染色质呈碎块状分散在胞质中。 核溶解（karyolysis）由于非特异性DNA酶和蛋白酶活化，使得DNA和核蛋白酶溶解破坏，细胞内PH降低，和染色质嗜碱性减弱，核淡染，仅能见到核的轮廓，在坏死后一两天内，细胞核完全溶解消失。 萎缩(atrophy)是指已发育正常的实质细胞、组织或器官体积缩小，可以伴发细胞数量的减少。 肥大(hypertrophy)由于功能增强，合成代谢旺盛，使实质细胞、组织器官体积增大。 增生(hyperplasia)组织、器官内实质细胞增殖，细胞数量增多的现象，成为增生。 化生(metaplasia)是一种分化成熟的细胞类型被另一种分化成熟细胞类型所取代的过程。 变性(degeneration)细胞或细胞间质受损伤后，由于代谢功能障碍，使细胞质内或细胞间质内呈现异常物质或正常物质过度积蓄的现象，常伴有细胞，组织或器官功能低下。 细胞水肿(cellular swelling)又称水变性（hydropic degeneration）是细胞可逆性损伤的一种形式，常是细胞损伤中最早出现的形态学改变，可由缺血,缺氧,感染和中毒引起，是钠-钾泵功能降低细胞内水分增多，胞质淡染、清亮，好发于肝、肾、心等实质器官。 脂肪变性(fatty degeneration or fatty change)指非脂肪细胞的实质细胞内中性脂肪（或甘油三酯）的异常蓄积称为脂肪变性。 细动脉硬化症（arteriolosclerosis）在长期高血压和糖尿病的影响下，细小动脉管壁，尤其是脑，肾脾的细动脉管壁，可发生玻璃样变，称为细动脉硬化症。 坏死(necrosis)①活体内；②局部细胞死亡；③细胞崩解、结构自溶；④急性炎反应。 凝固性坏死(coagulative necrosis)①坏死细胞蛋白质凝固；②保持原组织轮廓；③肉眼呈灰白、灰黄；④好发于心、肾、脾。 干酪样坏死(caseous necrosis，caseation)①属凝固性坏死；②不见原组织轮廓；③肉眼观似奶酪； ④多见于结核病。 液化性坏死(liquefactive necrosis)①坏死组织呈液态；②蛋白质少、脂质多的组织或溶解酶多的组织。 坏疽(gangrene)①较大范围的坏死；②腐败菌感染；③与外界相通的组织、器官；④分干性、湿性、气性三种。 凋亡(apoptosis)①活体内；②单个或小团细胞死亡；③死亡细胞的质膜不破裂，细胞不自溶；④无急性炎反应。 机化(organization)①肉芽组织；②吸收、取代坏死物或其他异物。 修复(repair)①机体部分细胞和组织的缺损；②周围健康细胞分裂、增生；③修补、恢复缺损的过程。 再生(regeneration)①损伤周围的同种细胞；②修补缺损。 肉芽组织(granulation tissue)①新生的毛细血管及成纤维细胞；②炎细胞浸润；③肉眼：鲜红色、颗粒状、柔软湿润，形似鲜嫩的肉芽。 创伤愈合(wound healing)①皮肤等组织的离断缺损；②组织的再生或增生所进行修复的过程。

病理学名词解释

病理学名词解释 注：该名词解释为人卫第八版（绪论、一、二、三、四、五、七、八及十六章第一节）的重点名词，重要程度蓝>红>黑。 1.活体组织检查（biopsy）：简称“活检”，即用局部切取、钳取、细针穿刺和搔刮等手术 方法，从活体内获取病变组织进行病理诊断，是目前诊断疾病广为采用的方法。 2.萎缩(atrophy)已发育正常的器官、组织或细胞体积缩小。 3.肥大(hypertrophy)由于功能增加，合成代谢旺盛，使细胞、组织或器官体积增大。 4.增生(hyperplasia)由于细胞有丝分裂活跃，使组织、器官内细胞数量增多，常造成组 织、器官的体积增大和功能活跃。 5.化生(metaplasia)一种分化成熟的细胞类型被另一种分化成熟的细胞类型取代的过程。 6.适应（adaptation）：细胞和由其构成的组织、器官对于内、外环境的持续性刺激和各 种有害因子而产生的非损伤性应答反应。 7.变性(degeneration)细胞或细胞间质受损伤后，由于代谢障碍,在细胞内或间质中出现异 常物质,或正常物质数量增多的现象。 8.细胞水肿(hydropic degeneration)水和钠离子积聚在细胞内。 9.脂肪变性(fatty change OR steatosis)甘油三酯蓄积于非脂肪细胞的细胞质中。 10.气球样变(ballooning degeneration)肝细胞高度水变性时,细胞肿大明显,细胞基质高度 疏松呈空泡状,细胞核也可肿胀，胞质膜表面出现囊泡，微绒毛变形消失，其极期称为气球样变。 11.虎斑心：脂肪变心肌呈黄色，与正常心肌的暗红色相间，形成黄红色斑纹。 12.玻璃样变(hyalinization)均质红染、半透明状的蛋白质蓄积于细胞内或间质中。 13.黏液样变(mucoid degernation蛋白质和黏多糖蓄积于细胞间质内。 14.坏死(necrosis)活体内局部组织以酶溶性为特点的细胞死亡。 15.凝固性坏死（coagulative necrosis）：溶酶体酶水解作用弱使蛋白质变性凝固，坏死 区灰黄、干燥、质实。 16.液化性坏死（liquefactive necrosis）：水解酶释放多使可凝固蛋白质少，或组织富含 水分和磷脂，细胞坏死发生溶解液化。 17.纤维素样变(纤维素样坏死)(fibrinoid necrosis)结缔组织及小血管壁的一种变性,病 变处组织结构消失,成为一堆颗粒状、细丝状、红染无结构的物质，状似纤维素。 18.干酪样坏死(caseous necrosis)是一种特殊类型的凝固性坏死,由于坏死组织中含较多 的脂质,外观呈淡黄色,松软,均匀细腻,似奶酪,称之。常见于结核病。 19.坏疽(gangrene)局部组织大范围的坏死,伴有不同程度的腐败菌感染,分为干性、湿性和 气性等类型。 20.糜烂（erosion）皮肤、黏膜浅表的组织缺损。 21.溃疡(u l c e r)皮肤、黏膜较深的组织缺损。 22.窦道(sinus)组织坏死后的只开口于皮肤黏膜表面的深在性盲管。 23.瘘管(fistula)连接两个内脏器官或从内脏器官通向体表的通道样缺损。 24.空洞（cavity）内脏坏死物液化后经自然管道排出所残留的空腔。 25.完全再生：由损伤的周围的同种细胞修复，使再生的细胞和组织完全保持原有的结构和 功能。 26.不完全再生：由纤维结缔组织修复,损伤组织被增生肉芽组织所代替,最后形成疤痕。 27.肉芽组织（granulation tissue）：由新生薄壁的毛细血管以及增生的成纤维细胞构成，