GFAP promoter-controlled EGFP-expressing transgenic mice: a tool to visualize astrocytes and astrogliosis in living brain tissue

We have generated transgenic mice in which astrocytes are labeled by the enhanced green fluorescent protein (EGFP) under the control of the human glial fibrillary acidic protein (GFAP) promoter. In all regions of the CNS, such as cortex, cerebellum, striatum, corpus callosum, hippocampus, retina, and spinal cord, EGFP-positive cells with morphological properties of astrocytes could be readily visualized by direct fluorescence microscopy in living brain slices or whole mounts. Also in the PNS, nonmyelinating Schwann cells from the sciatic nerve could be identified by their bright green fluorescence. Highest EGFP expression was found in the cerebellum. Already in acutely prepared whole brain, the cerebellum appeared green-yellowish under normal daylight. Colabeling with GFAP antibodies revealed an overlap with EGFP in the majority of cells. Some brain areas, however, such as retina or hypothalamus, showed only low levels of EGFP expression, although the astrocytes were rich in GFAP. In contrast, some areas that were poor in immunoreactive GFAP were conspicuous for their EGFP expression. Applying the patch clamp technique in brain slices, EGFP-positive cells exhibited two types of membrane properties, a passive membrane conductance as described for astrocytes and voltage-gated channels as described for glial precursor cells. Electron microscopical investigation of ultrastructural properties revealed EGFP-positive cells enwrapping synapses by their fine membrane processes. EGFP-positive cells were negative for oligodendrocyte (MAG) and neuronal markers (NeuN). As response to injury, i.e., by cortical stab wounds, enhanced levels of EGFP expression delineated the lesion site and could thus be used as a live marker for pathology.     

Effects of diabetes mellitus on astrocyte GFAP and glutamate transporters in the CNS

Diabetes mellitus increases the risk of central nervous system (CNS) disorders such as stroke, seizures, dementia, and cognitive impairment. The cellular mechanisms responsible for the increased risk of these disorders are incompletely understood. Astrocytes are proving critical for normal CNS function, and alterations in their activity could contribute to diabetes-related disturbances in the brain. We examined the effects of streptozotocin (STZ)-induced diabetes in rats on the level of the astrocyte intermediate filament protein, glial fibrillary acidic protein (GFAP), number of astrocytes, and levels of the astrocyte glutamate transporters, glutamate transporter-1 (GLT-1) and glutamate/aspartate transporter (GLAST), in the cerebral cortex, hippocampus, and cerebellum by Western blotting (WB) and immunohistochemistry (IH). Studies were carried out at 4 and 8 weeks of diabetes duration. Diabetes resulted in a significant decrease in GFAP protein levels (WB) in the hippocampus and cerebellum at 4 weeks and in the cerebral cortex, hippocampus and cerebellum by 8 weeks. Attenuated GFAP immunoreactivity (IH) was evident in the hippocampus, cerebellum and white matter regions such as the corpus callosum and external capsule at both 4 and 8 weeks of diabetes. Astrocyte cell counts of adjacent sections immunoreactive for S-100B were not different between control and diabetic animals. No significant differences were noted in astrocyte glutamate transporter levels in the cerebral cortex, hippocampus, or cerebellum at either time period (WB, IH). With the expanding list of astrocyte functions in the CNS, the role of astrocytes in diabetes-induced CNS disorders clearly warrants further investigation.     

Central Nervous System Complications of Diabetes in Streptozotocin-Induced Diabetic Rats: A Histopathological and Immunohistochemical Examination

Diabetes mellitus is a common, potentially serious metabolic disorder. Over the long term, diabetes leads to serious consequences in a number of tissues, especially those that are insulin insensitive (retina, neurons, kidneys). It also causes a variety of functional and structural disorders in the central and peripheral nervous systems. We investigated whether neurodegenerative changes were observable in the hippocampus, cortex, and cerebellum after 4 weeks of streptozotocin (STZ)-induced diabetes in rats and the effect(s) of melatonin. Male Wistar rats (n = 32) were divided into four groups (n = 8 each): untreated controls, melatonin-treated controls, untreated diabetics, and melatonin-treated diabetics. Experimental diabetes was induced by a single dose of STZ (60 mg/kg, intraperitoneal (ip)). For 3 days before the administration of STZ, melatonin (200 μg/kg/day, ip) was injected and continued for 4 weeks. Sections of hippocampus, cortex, and cerebellum were stained with hematoxylin and eosin and examined using light microscopy. In addition, brain tissues were examined immunohistochemically for the expression of glial and neuronal markers, including glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), and heat shock protein-70 (HSP-70). No neurodegenerative changes were observed in the hippocampus, cortex, or cerebellum of the untreated diabetic group after 4 weeks compared with the other groups. We did not observe any change in GFAP, NSE, or HSP-70 immunostaining in the brain tissues of STZ-induced diabetic rats. In summary, after 4 weeks of STZ-induced diabetes in rats, no degenerative or immunohistochemical changes were detected in the hippocampus, cortex, or cerebellum.     

Evidence of astrogliosis in rat hippocampus after d-amphetamine exposure

INTRODUCTION: Psychostimulants such as amphetamine (AMPH) induce manic-like symptoms in humans and studies have suggested that bipolar disorder (BD) may be associated to dopamine dysfunction. Glial fibrillary acidic protein (GFAP) up-regulation is considered a marker of astrogliosis, and it has been associated to behavioral sensitization. PURPOSE: We aimed to investigate the behavioral effects of acute and chronic AMPH on rat locomotion and assess GFAP levels in rat cortex and hippocampus. METHODS: Rats were administered either acute (single dose) or chronic (seven days) d-amphetamine IP injection. Locomotion was assessed with an open-field test and GFAP immunoquantity was measured using ELISA. RESULTS: Chronic, but not acute, administration of AMPH increased GFAP levels in rat hippocampus. No differences were observed in rat cortex. CONCLUSIONS: Repeated exposure to AMPH leads to an astroglial response in the hippocampus of rats.     

Alteration in hippocampal and cerebral expression of glial fibrillary acidic protein following styrene exposure in rat

In order to investigate the neuropathological effects on the central nervous system of the rat by styrene exposure, identification of glial fibrillary acidic protein (GFAP) was observed using immunohistochemical staining and confocal laser scanning microscopy in the rat treated with styrene at 400 mg/kg and 800 mg/kg for 2 weeks. Both styrene-treated groups showed a marked increase of GFAP expression in cerebral cortex and hippocampus compared with the control group. These changes showed a dose- and time-dependent manner. Increased expression of GFAP in cerebral cortex and hippocampus provided the effects of styrene on the structüre of cerebral cortex and hippocampus objectively.     

Cortical expression of glial fibrillary acidic protein and glutamine synthetase is decreased in schizophrenia

Altered expression of structural and functional molecules expressed by astrocytes may play a role in the pathophysiology of schizophrenia. We investigated the hypothesis that the astrocytic enzyme glutamine synthetase, involved in maintaining the glutamate-glutamine cycle, and the cytoskeletal molecule glial fibrillary acidic protein (GFAP) are abnormally expressed in schizophrenia. We used Western blot analysis to measure levels of glutamine synthetase and GFAP in several brain regions of subjects with schizophrenia and a comparison group. We found that glutamine synthetase protein expression was significantly decreased in the superior temporal gyrus, and both glutamine synthetase and GFAP were significantly reduced in the anterior cingulate cortex in schizophrenia. Neither molecule demonstrated altered expression in the dorsolateral prefrontal cortex, primary visual cortex, or hippocampus. Chronic treatment with haloperidol did not alter the expression of these molecules in the rat brain, suggesting that our findings are not due to a medication effect. These data support an astrocytic component to the pathophysiology of schizophrenia and suggest that astrocytic molecules involved in enzymatic activity and cytoskeletal integrity may have a role in disease-related abnormalities in this illness.     

Expression of Na(+)-K(+)-Cl(-) cotransporter in rat brain during development and its localization in mature astrocytes

Na(+)-K(+)-Cl(-) cotransporter has been proposed to play an important role in the regulation of intracellular Cl(-) concentration in neurons during development. In this study, the expression pattern of the cotransporter in different regions of rat brain was examined at birth (P0), postnatal days 7 (P7), P14, P21, and adult by Western blotting analysis. In cortex, thalamus, cerebellum and striatum, the cotransporter expression level was low at P0 and significantly increased at P14 (P<0.05). The expression peaked at P21 and was maintained at the same level in adulthood. However, in hippocampus, a peak level of the cotransporter expression was detected in adult brain. The immunocytochemistry study of adult rat brain revealed that an intense staining of the Na(+)-K(+)-Cl(-) cotransporter protein was observed in dendritic processes of CA1-CA3 hippocampal pyramidal neurons. In contrast, abundant immuno-reactive signals of the cotransporter were found in somata of thalamic nucleus. Immunofluorescence double staining demonstrates that the Na(+)-K(+)-Cl(-) cotransporter was expressed in astrocytes within cortex, corpus callosum, hippocampus and cerebellum. In addition, co-localization of the cotransporter and glial fibrillary acidic protein (GFAP), or with aquaporin 4, was found in perivascular astrocytes of cortical cortex and white matter. The results indicate that a time-dependent expression of the Na(+)-K(+)-Cl(-) cotransporter protein occurs not only in cortex but also in hippocampus, striatum, thalamus and cerebellum. In addition, the cotransporter is expressed in astrocytes and perivascular astrocytes of adult rat brain.     

戊四氮点燃慢性癫痫大鼠海马及颞叶皮质γ-氨基丁酸转运体1及胶质纤维酸性蛋白的表达

BACKGROUND： Gamma-aminobutyric acid transporter plays an important role in gamma-aminobutyric acid metabolism, and is highly associated with epilepsy seizures. Pathologically, astrocytes release active substances that alter neuronal excitability, and it has been demonstrated that astrocytes play a role in epileptic seizures. OBJECTIVE： To observe changes in gamma-aminobutyric acid transporter 1 and glial fibrillary acidic protein expression in the hippocampus and cortex of the temporal lobe in rats with pentylenetetrazol-induced chronic epilepsy. DESIGN, TIME AND SETTING： Randomized, controlled, animal experiment was performed at the Department of Neurobiology, Third Military University of Chinese PLA between January 2006 and December 2007. MATERIALS： Pentylenetetrazol was purchased from Sigma, USA; rabbit anti-rat gammaaminobutyric acid transporter 1 and glial fibrillary acidic protein were from Chemicon, USA. METHODS： A total of 40 Sprague Dawley rats were divided into model and control groups. Rat models of chronic epilepsy were created by pentylenetetrazol kindling, and were subdivided into 3-, 7-, and 14-day kindling subgroups. MAIN OUTCOME MEASURES： Gamma-aminobutyric acid transporter 1 and glial fibrillary acidic protein expression, as well as the number of positive cells in the hippocampus and cortex of temporal lobe of rats, were determined by immunohistochemistry and Western blot analyses. RESULTS： Compared with the control group, the number of gamma-aminobutyric acid transporter 1 and glial fibrillary acidic protein -positive cells in the hippocampus and cortex of rats with pentylenetetrazol-induced epilepsy significantly increased, gamma-aminobutyric acid transporter 1 and glial fibrillary acidic protein expression increased after 3 days of kindling, reached a peak on day 7, and remained at elevated levels at day 14 （P〈 0.05）. CONCLUSION： Astrocytic activation and gamma-aminobutyric acid transporter 1 overexpression may contribute to pentylenetetrazol-induced epilepsy.     

Long-term astroglial reaction to serotonergic fiber degeneration

Glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS) expression were analysed by Western and Northern blotting in the hippocampus, the frontal and occipital cortex, and the cerebellum of the adult rat, as a manifestation of the astroglial reaction, 2 and 3 months after 5,7-dihydroxytryptamine injection into the lateral ventricule. 5HT injury stimulated GFAP and GS expression in a temporally and regionally specific fashion. At 2 months postlesion, the GFAP-mRNA and GFAP levels appeared enhanced but returned to control levels at 3 months. The GFAP-mRNA and GS-mRNA levels increased in the frontal cortex at 3 months. Such a delayed astroglial reactivity might implicate astrocytes in neurodegenerative disorders.     

Messenger RNA for glial fibrillary acidic protein is decreased in rat brain following acute and chronic corticosterone treatment

RNA coding for a 50 kDa polypeptide decreased by 50% in 5 brain regions after corticosterone (CORT) treatment (40 mg/kg for 3 days). By hybrid selection and in vitro translation, the 50 kDa polypeptide is identified as glial fibrillary acidic protein (GFAP). Hippocampal GFAP mRNA (2.9 kb) decreases in a dose-dependent manner in response to CORT by RNA blot hybridization using a mouse GFAP cRNA probe; a similar decrease in response to the glucocorticoid agonist, RU 28362, is consistent with a type II glucocorticoid receptor-mediated effect. GFAP mRNA is decreased in both hippocampus and cortex following acute (1-3 days) and chronic (3 days to 3 months) CORT treatment. GFAP gene expression is disinhibited in the rat hippocampus by 7 days post adrenalectomy but not by 3 days. Finally, two clones (CR46 and CR59) that were isolated from a rat hippocampal cDNA library by differential hybridization, show decreased RNA abundance in CORT-treated rats compared to controls. A partial DNA sequence derived from the two clones exhibits 94% nucleotide identity and 96% derived amino acid identity with mouse GFAP mRNA. These results indicate that GFAP mRNA is under negative regulation by glucocorticoids and suggests that glucocorticoids may be used to inhibit GFAP gene expression in vivo in order to assess the role of GFAP in temporal aspects of central nervous system damage.     

Zn and Cu alteration in connection with astrocyte metallothionein I/II overexpression in the mouse brain upon physical stress

The distribution of metallothioneins I/II in the mouse brain and their specific area distribution upon physical stress were studied. To induce physical stress, groups of mice were subjected to total darkness for different periods (2 weeks, 1 month, and 2 months). The concentration of metallothioneins, evaluated by immunohistochemistry, as well as area-specific protein expression, were found in the following quantitative order: corpus striatum, cerebellum, mesencephalon, hippocampus with fornix, parts of thalamus, and pons. All other brain areas were marginally affected, or even unaffected, in terms of immunopositive metallothionein reaction. Metallothionein I/II expression was compared with the immunopositivity of glial fibrillary acidic protein (GFAP). It is noteworthy that metallothioneins and GFAP are expressed in different types of astrocytes.     

Transient ischemia stimulates glial fibrillary acid protein and vimentin gene expression in the gerbil neocortex, striatum and hippocampus.

Astrocytic activation plays a major role in homeostatic maintenance of the central nervous system in response to neuronal damage. To assess the reactivity of astrocytes in transient cerebral ischemia of the gerbil, we studied the levels of glial fibrillary acidic protein (GFAP) and its mRNA. GFAP mRNA increased by 4 h after carotid artery occlusion, reached peak levels by 72 h with a 12-fold increase over control and then started declining as early as 96 h postischemia. An examination of the specific regions of the brain revealed an increase in GFAP mRNA associated with the forebrain, midbrain, hippocampus and striatum. GFAP mRNA in the non-ischemic cerebellum however, remained expressed at constitutively low levels. Immunoblot analysis with anti-GFAP antibodies demonstrated a 2- to 3-fold increase in the protein after 24 and 48 h of reperfusion. Pretreatment with pentobarbital and 1-(5'-oxohexyl)-3-methyl-7-propyl xanthine (HWA 285), the drugs that have been shown to protect against ischemic damage, prevented the increase in GFAP mRNA in the cortex following ischemic injury. Forebrain ischemia also induced vimentin mRNA and protein quantities by 12 h of reperfusion in the cortex. The levels of c-fos and preproenkephalin mRNA increased rapidly within 1 h after ischemic injury, demonstrating a temporal difference in mRNA changes following ischemia. These results indicate that an increase in GFAP and vimentin, the two glial intermediate filament proteins in the area of the ischemic lesion may be associated with a glial response to injury.     

颞叶内侧癫痫患者海马区胶质细胞中GFAP、GLAST和GLT-1的表达

目的研究胶质纤维酸性蛋白(GFAP)及谷氨酸-胱氨酸转运体(GLAST)、神经胶质谷氨酸转运体(GLT-1)在颞叶癫痫患者海马区的表达情况。方法取40例难治性颞叶内侧癫痫患者在手术中切除的海马组织,根据在光镜下观察到的神经元丢失情况,分为海马硬化组(A组)23例和海马非硬化组(B组)17例,通过免疫组化法检测两组GFAP、GLAST、GLT-1的表达情况。结果A组GFAP的表达与B组比较,总海马区域、CA1区、CA2区、齿状回表达增加(P<0.01)。A组GLAST的表达与B组比较,海马总区域、齿状回差异无显著性(P>0.05)、CA1区减少(P<0.05)、CA2区则增加(P<0.05)。A组GLT-1的表达与B组比较,总海马区域、CA1区减少(P<0.01)、CA2区增加(P<0.01),齿状回差异无显著性(P>0.05)。结论颞叶内侧癫痫患者海马各区GFAP表达增加,GLAST、GLT-1在海马CA1区减少、CA2区表达增加,提示癫痫发作后海马区谷氨酸转运体重新分布可能是难治性癫痫发病机制之一。     

Protective effects of melatonin against ethanol-induced reactive gliosis in hippocampus and cortex of young and aged rats

Evidence has been accumulated indicating that chronic ethanol consumption leads to direct or indirect changes in the viability of central nervous system cells. The effects of aging and chronic ethanol consumption on glial markers [glial fibrillary acidic protein (GFAP) and S100B] and oxidant and antioxidant status of rats were studied. Furthermore, protective effects of melatonin against aging and alcohol consumption were also assayed. Chronic ethanol administration to young and aged rats produced an increase in lipid peroxidation, and a decline in glutathione (GSH) levels, which was significantly reversed by the co-administration of melatonin. Lipid peroxidation status was markedly affected in aged rats treated with alcohol compared to the young rats. An age-related increase in GFAP and S100B levels were found in the cortex and hippocampus. Long-term alcohol exposure resulted in distinct elevation in GFAP content in young rats (P < 0.01) while there was less increase in the cortex of aged rats (P < 0.05). In old rats, hippocampal GFAP levels were not significantly changed by alcohol treatment (P > 0.05). Co-administration of melatonin with alcohol significantly reduced GFAP contents both in the hippocampus (P < 0.01) and cortex (P < 0.001) of aged rats. No significant effects of alcohol treatment were found on the levels of neuron-specific enolase (NSE) in aged rats. This finding suggests that melatonin exerts its protective effect on injured nervous tissues by scavenging free radicals and stabilizing glial activity against the damaging effects of ethanol and aging. Furthermore, this work suggests that the signal to initiate gliosis is mediated, at least indirectly, by free radical formation.     

Corticosterone differentially regulates the bilateral response of astrocyte mRNAs in the hippocampus to entorhinal cortex lesions in male rats.

This study examined the effect of adrenalectomy (ADX) and corticosterone (CORT) replacement on the levels of two astrocyte mRNAs during responses to unilateral entorhinal cortex lesions (ECL) to identify molecular mechanisms involved in glucocorticoid modulation of astrocyte activation following deafferentation. Both glial fibrillary acidic protein (GFAP) and sulfated glycoprotein-2 (SGP-2) mRNA were increased in the ipsilateral hippocampus 4 days following unilateral ECL. In unlesioned ADX rats CORT replacement decreased both messages in the hippocampus. CORT replacement suppressed the ECL-induced increase of GFAP mRNA in the contralateral, but not ipsilateral hippocampus of ADX rats. In contrast, CORT decreased SGP-2 mRNA both ipsi- and contralaterally. It is clear that several regulatory mechanisms are responsible for maintaining a physiological balance of astrocyte activity in the adult brain, and that changes in circuit integrity and the endocrine milieu can alter this balance.     

Developmental expression of glial fibrillary acidic protein mRNA in the rat brain analyzed by in situ hybridization

Glial fibrillary acidic protein (GFAP) accumulates in astrocytes during development. We have characterized the increase in GFAP mRNA during development of the rat brain by using Northern blotting and in situ hybridization histochemistry and have found a caudal to rostral gradient of expression, consistent with overall brain maturation. GFAP mRNA was first observed at embryonic day 16 (E16) in the glial limitans of the ventral hindbrain. During brain development message levels increased rostrally and by postnatal day 5 (P5) the entire glial limitans showed a positive signal which persisted into adulthood. GFAP mRNA was also found to accumulate in a caudal to rostral direction within the Purkinje cell layer of cerebellum beginning shortly after birth. By P5 the entire layer was positive and signal in this region could be localized to Bergmann glia by P15. A transient elevation in GFAP mRNA was apparent during the second postnatal week in cerebellum and cerebrum. Using in situ hybridization, a peak in message levels was observed at P15 and could be localized primarily to the deep white matter of cerebellum, to the corpus callosum, and to certain hippocampal fiber tracts. The pattern of GFAP expression in these regions is consistent with the differentiation of interfascicular glia and the appearance of type-2 astrocytes during the initial events of myelination. GFAP mRNA levels in white matter were greatly reduced in the adult. The pronounced regional differences in GFAP mRNA expression during development may reflect the differentiation of subpopulations of astrocytes.     

Co-expression of glial fibrillary acidic protein and vimentin in reactive astrocytes following brain injury in rats.

The immunohistochemical expression of glial fibrillary acidic protein (GFAP) and vimentin (VIM) was studied in reactive astrocytes of the rat cerebral cortex 5 days after a brain injury. Seriated Epon semithin sections were immunostained alternatively for GFAP or VIM. Thereafter, both antigens were detected in consecutive sections of the same cell. Bordering the wound, an inner reactive glial layer 300-350 microns thick, showed positive astrocytes with the two immunohistochemical techniques. In this layer, about 60% of the GFAP positive astrocytes were also positive for VIM. Outside the inner layer, only GFAP positive astrocytes could be found.     

血栓素A_2受体在正常大鼠脑内的分布定位

目的探讨血栓素A2受体(TP)在正常大鼠脑内的表达分布特点。方法正常成年SD大鼠脑组织冰冻切片,TP免疫荧光染色,TP/神经核蛋白(Neu N),TP/胶质纤维酸性蛋白(GFAP),TP/谷氨酸脱羧酶67(GAD67)免疫荧光双标染色,观察TP在脑内分布表达情况。结果 TP免疫阳性产物主要分布在扣带回皮质、皮层Ⅲ~V层、下丘和小脑的浦肯野细胞层;免疫荧光双标结果显示TP与神经元胞核特异性标记物Neu N共存,但不与星形胶质细胞标记物GFAP共存;同时,所有TP阳性神经元表达γ氨基丁酸(GABA)能神经元标记物GAD67。结论 TP表达于大鼠扣带回皮质、皮层Ⅲ~V层、下丘脑和小脑的浦肯野细胞层,主要分布于GABA能神经元,提示TP可能参与了大鼠大脑GABA能神经元的功能调节和病变过程。     

Profound increase in sensitivity to glutamatergic- but not cholinergic agonist-induced seizures in transgenic mice with astrocyte production of IL-6

Transgenic mice with glial fibrillary acidic protein (GFAP) promoter driven-astrocyte production of the cytokines interleukin-6 (IL-6) and tumor necrosis factor (TNF) were used to determine whether the pre-existing production of these cytokines in vivo might modulate the sensitivity of neurons to excitotoxic agents. Low doses of kainic acid (5 mg/kg) that produced little or no behavioral or electroencephalogram (EEG) alterations in wild type or glial fibrillary acidic protein (GFAP)-TNF animals induced severe tonic-clonic seizures and death in GFAP-IL6 transgenic mice of 2 or 6 months of age. GFAP-IL6 mice were also significantly more sensitive to N-methyl-D-aspartate (NMDA)- but not pilocarpine-induced seizures. Kainic acid uptake in the brain of the GFAP-IL6 mice was higher in the cerebellum but not in other regions. Kainic acid binding in the brain of GFAP-IL6 mice had a similar distribution and density as wild type controls. In the hippocampus of GFAP-IL6 mice that survived low dose kainic acid, there was no change in the extent of either neurodegeneration or astrocytosis. Immunostaining revealed degenerative changes in gamma aminobutyric acid (GABA)- and parvalbumin-positive neurons in the hippocampus of 2-month-old GFAP-IL6 mice which progressed to the loss of these cells at 6 months of age. Thus, GFAP-IL6 but not GFAP-TNF mice showed markedly enhanced sensitivity to glutamatergic- but not cholinergic-induced seizures and lethality. This may relate, in part, to a compromise of inhibitory interneuron function. Therefore, pre-existing IL-6 production and inflammation in the central nervous system (CNS) not only causes spontaneous neurodegeneration but also synergizes with other neurotoxic insults to induce more severe acute functional neurological impairment.     

Hippocampal kindling alters the concentration of glial fibrillary acidic protein and other marker proteins in rat brain

The effect of hippocampal kindling on neuronal and glial marker proteins was studied in the rat by immunochemical methods. In hippocampus, pyriform cortex and amygdala there was an increase in glial fibrillary acidic protein (GFAP), indicating reactive gliosis, and an increase in the glycolytic enzyme NSE, suggesting increased anaerobic metabolism. Neuronal cell adhesion molecule (NCAM) decreased in pyriform cortex and amygdala of kindled rats, indicating neuronal degeneration.