FOXG1 Directly Suppresses Wnt5a During the Development of the Hippocampus / 神经科学通报·英文版

The Wnt signaling pathway plays key roles in various developmental processes. Wnt5a, which activates the non-canonical pathway, has been shown to be particularly important for axon guidance and outgrowth as well as dendrite morphogenesis. However, the mechanism underlying the regulation of Wnt5a remains unclear. Here, through conditional disruption of Foxg1 in hippocampal progenitors and postmitotic neurons achieved by crossing Foxg1

Immature neurons born one week before pilocarpine-induced status epileptic exhibit aberrant integration at chronic stage after SE / 西安交通大学学报(医学版)

Objective To determine whether the integration of immature neurons born before status epilepticus (SE)can be disrupted by an epileptogenic insult.Methods Pilocarpine was used to induce SE in mice. At week 1 before induction,BrdU or retroviral vector expressing green fluorescent protein (RV-GFP)was used to label the newly born cells in the dentate gyrus (DG).At week 8 after SE,BrdU+Map2 or BrdU+NeuN double-labeling staining was carried out to visualize hilar basal dendrite or hilar ectopic migration.Virus-transduced GFP signals were used to identify the mossy fiber sprouting from the newly generated neurons.The number of cells with aberrant integrations was compared using unpaired Student's t-test.Results The percentage of newborn neurons with aberrant dendritic morphology was (20.8±8.4)% at week 8 after SE.The percentage of BrdU+NeuN double labeled cells ectopically migrated into the hilus was (15.9 ± 7.4)%.At week 8 after SE,the chronically epileptic mice showed many GFP+ processes in the IML with the same axonal appearance and small mossy fiber bouton-like structures as those seen in the hilus.The number of newborn neurons with aberrant integrations in SE mice wassignificantly increased when compared with the control mice (P <0.05).Conclusion These data demonstrate the existence of aberrant integrations-hilar basal dendrites,hilar ectopic migration and mossy fiber sprouting in the DG-generated cells born 1 week before an SE insult.

Immature neurons born one week before pilocarpine-induced status epileptic exhibit aberrant integration at chronic stage after SE / 西安交通大学学报(医学版)

Objective To determine whether the integration of immature neurons born before status epilepticus (SE)can be disrupted by an epileptogenic insult.Methods Pilocarpine was used to induce SE in mice. At week 1 before induction,BrdU or retroviral vector expressing green fluorescent protein (RV-GFP)was used to label the newly born cells in the dentate gyrus (DG).At week 8 after SE,BrdU+Map2 or BrdU+NeuN double-labeling staining was carried out to visualize hilar basal dendrite or hilar ectopic migration.Virus-transduced GFP signals were used to identify the mossy fiber sprouting from the newly generated neurons.The number of cells with aberrant integrations was compared using unpaired Student's t-test.Results The percentage of newborn neurons with aberrant dendritic morphology was (20.8±8.4)% at week 8 after SE.The percentage of BrdU+NeuN double labeled cells ectopically migrated into the hilus was (15.9 ± 7.4)%.At week 8 after SE,the chronically epileptic mice showed many GFP+ processes in the IML with the same axonal appearance and small mossy fiber bouton-like structures as those seen in the hilus.The number of newborn neurons with aberrant integrations in SE mice wassignificantly increased when compared with the control mice (P <0.05).Conclusion These data demonstrate the existence of aberrant integrations-hilar basal dendrites,hilar ectopic migration and mossy fiber sprouting in the DG-generated cells born 1 week before an SE insult.

Immunohistochemical Localization of Translationally Controlled Tumor Protein in Axon Terminals of Mouse Hippocampal Neurons

Translationally controlled tumor protein (TCTP) is a cytosolic protein with microtubule stabilization and calcium-binding activities. TCTP is expressed in most organs including the nervous system. However, detailed distribution and functional significance of TCTP in the brain remain unexplored. In this study, we investigated the global and subcellular distributions of TCTP in the mouse brain. Immunohistochemical analyses with anti-TCTP revealed that TCTP was widely distributed in almost all regions of the brain including the cerebral cortex, thalamus, hypothalamus, hippocampus, and amygdala, wherein it was localized in axon tracts and axon terminals. In the hippocampus, TCTP was prominently localized to axon terminals of the perforant path in the dentate gyrus, the mossy fibers in the cornu ammonis (CA)3 region, and the Schaffer collaterals in the CA1 field, but not in cell bodies of granule cells and pyramidal neurons, and in their dendritic processes. Widespread distribution of TCTP in axon tracts and axon terminals throughout the brain suggests that TCTP is likely involved in neurotransmitter release and/or maintaining synaptic structures in the brain, and that it might have a role in maintaining synaptic functions and synaptic configurations important for normal cognitive, stress and emotional functions.

Effects of Pilocarpine-induced Seizures on the Neuronal Cell Death, Mossy Fiber Sprouting and Neurogensis in the Hippocampus of Mice / 체질인류학회지

Present study was performed to delineate the inter-relationship among neuronal death, mossy fiber sprouting (MFS) and neurogenesis in hippocampal formation of pilocarpine-treated mice. Status epilepticus was induced by intraperitoneal administration of 300 mg/kg pilocarpine in male ICR and C57BL/6 mouse. The severity of seizure was evaluated using 5 grades of Racine scales for first 4 hr after pilocarpine injection. Fluro-Jade C (FJC) staing, NeoTimm's staining and immunohistochemistry for BrdU were employed to evaluate neuronal cell death, MFS and neurogenesis, respectively. All animals in the present study induced seizures over grade 3 of Racine scale by pilocarpine injection. ICR mice show higher seizure severity (mean Racine scale; 4.37) than C57BL/6 mice do (mean Racine scale; 3.22), while the latency times for the first seizure over Racine scale grade 3 are from 15 min to 20 min and showed no difference between the 2 strains. In ICR mouse, numerous FJC-positive cells in hilus of hippocampus were detected at 4 h after pilocarpine injection, while they were not detected at that time in C57BL/6 mouse. The number of FJC-positive neuronal cells, which were densely found in the pyramidal layer of CA1, CA3 and hilus polymorphic regions of hippocampus, reached peak at 3 days after injection and then few cells were found at 7 days after injection in both strains. In control animals, BrdU positive cells in dentate subgranular layer which represent the hippocampal neurogenesis were more numerous in C57BL/6 than in ICR. The number of BrdU positive cells significantly increased at 2 days after pilocarpine injection and reached the peak at 8 days after injection and returned to control level at 15 day after injection in both strains. The percent increase of the BrdU positive cell was more prominent in ICR mouse. MFS was found at 2 weeks after the injection and the intensity of MFS was getting strong at 4 weeks after injection. There was no differences in MFS grading between 2 strains. These results suggest that there are some inter-relationships among the seizure severity, hippocampal neuronal cell death and hippocampal neurogenesis, but they don't have any significant relationships with the mossy fiber sprouting from dentate granule cells.

Effects of transplanting neural stem cells transfected with cardiotrophin-1 on the injured hippocampus and mossy fiber sprouting in status epilepticus rats / 中华神经科杂志

Objective To observe the survival,migration and differentiation of grafted neural stem cells(NSCs)transfected with cardiotrophin-1(CT1)in hippocampus in status epilepticus(SE)rats,and investigate its effect on neuron loss and mossy fiber sprouting(MFS)in hippocampus of SE rats.Methods (1)Lithium-pilocarpine induced SE model rats were divided into 3 groups randomly:CT1-NSCs transplantation group(n=18);NScs transplantation group(n=18)and SE model group(n=18).Another 18 rats served as normal control group.Each group was further divided into 3 time points testing groups(n=6 at each point)corresponding to 1,4 and 8 weeks after transplantation respectively.(2)Under the confocal microscopy,the survival,migration and differentiation of the grafted cells were observed by immunofluorescenee.(3)Morphological changes and neuron loss in the hippocampal CA1 region were examined by Nissl staining.(4)MFS in hippocampal dentate gyrus in rats was obserred by Timm histochemistry.Results(1)At 4 and 8 weeks post-tmusplantation,the numbers of double-labeled NF-200 and EGFP pesitive cells in the CT1-NSCs group were significantly hisher than those in NSCs group.In the former group most of the grafted NSCs migrated away from the needle tract,but in the latter group,grafted ceHs remained at the transplantation site.(2)The numbers of neuron in the hippocampal CA1 region reduced gradually after SE.The numbers of neuron in the CA1 region in CT1-NSCs transplantation rats (68.85±11.49,60.89±12.17 and 51.51±13.34 in 1,4,8 weeks after transplantation respectivelv)were greater than that in NSCs transplantation rats(67.92±10.78,42.56±11.47 and 30.49±10.12).tvalue were 4.650 and 5.334 in 4 and 8 weeks after transplantation(P<0.05).(3)Aberrant MFS in the inner molecular layer of dentate gyrus was observed,and the scores of MFS gradually increased with timelapse.The scores of MFS in CT1-NSCs transplantation rats(0.77±0.04,2.48±0.89 and 2.39±0.82 in 1,4,8 weeks after transplantation respectively)were significant lower than that in NSCs transplantation rats (1.12±0.62,3.17±0.64 and 3.88±0.51,t=6.059,9.511 and 9.728,P<0.05).Conclusions CT1 could promote the survival,migration and differentiation of engrafted NSCs in hippocampud in SE rats.Engrafted NSCs transfected with CT1 have effect on repair of the injured hippocampus,and could inhibit hippocampus MFS in SE rats.

Comparison of Behavioral and Histological Changes between Pilocarpine-Induced Temporal Epilepsy Model and Pentylenetetrazole Kindling Absence Model in Rats / 中国康复理论与实践

@#ObjectiveTo investigate and compare the behavioral changes, neuron loss of hippocampus and mossy fiber sprouting between pilocarpine-induced status epilepticus (SE) model and pentylenetetrazole (PTZ) kindling model in rats.MethodsAfter two different epilepsy models were made, Vedio was adopted to observe the behavioral changes. Nissl staining and Neo-timms' staining were separately used to observe and compare the neuron loss of hippocampus and mossy fiber sprouting in the dentate gyrus (DG) at different time points during epileptogenisis.ResultsNo recurrent spontaneous seizure, no neuron loss and no mossy fiber sprouting were found in PTZ kindling model; whereas obvious neuron loss was found in CA1, CA3 of hippocampus and hilus of DG, and mossy fiber sprouting were found in pilocarpine model in parallel with recurrent spontaneous seizures. ConclusionPTZ kindling model resembles absence epilepsy in human, while pilocarpine-induced status epilepticus model resembles chronic temporal epilepsy in human. Neuron loss and mossy fiber sprouting may play an important role in epileptogenisis. Pilocarpine-induced epilepsy model can be regarded as an ideal chronic temporal epilepsy model.

Interference effect of Kangxianzengzhi capsule on hippocampal mossy fiber sprouting in epileptic rat kindled by pentylenetetrazol / 中华中医药杂志

To explore the interference effect of Kangxianzengzhi(KXZZ) capsule on hippocampal mossy fiber sprouting in epileptic rat kindled by pentylenetetrazol.Methods: Epileptic rat models were established by pentylenetetrazol(PTZ) kindling method.All rats were divided into six groups: KXZZ high-does group,KXZZ middle-does group,KXZZ low-does group,valproate magnesium group, model group and normal group randomly.Then the hippocampal mossy fiber sprouting was monitored by Timm stain method.Results: Mossy fiber sprouting was obvious in the hippocampal CA3 section and the molecular layer of dentate syrus in model group.Compared with normal group,the percent of sprouting density in model group was higher(P

The Role of MMP-9 on the Hippocampal Neuronal Cell Death and Mossy Fiber Sprouting due to Pilocarpine-Induced Status Epilepticus in Mice / 대한간질학회지

PURPOSE: Matrix metalloproteinases (MMPs) have been known to participate in various pathologic situations by modulating extracellular matrix. Although MMP-9 upregulation has been reported in some experimental seizure models, the exact role of MMP-9 in hippocampal cell death during epileptogenesis and subsequent mossy fiber sprouting (MFS) is not clear. Here, we investigated the role of MMP-9 on hippocampal cell death and MFS after pilocarpine-induced status epilepticus (SE) in mice, using highly specific hydroxamic MMP-9 inhibitor. METHODS: SE was induced by intraperitoneal pilocarpine administration in adult male C57BL/6 mice. MMP-9 specific inhibitor was administered intracerebroventrically 3 h after pilocarpine-induced SE. Expression and activation of MMP-9 were assessed by zymography and Western blot analysis. TdT-mediated UTP-biotin nick end labeling (TUNEL) and caspase-3 activity assay were also performed. MFS was investigated using Timm staining. RESULTS: Increased expression and activation of MMP-9 after pilocarpine-induced SE were observed in zymography and Western blot analysis. MMP-9 specific inhibitor decreased MMP-9 activity in in situ zymography and hippocampal cell death in cresyl violet staining. DNA fragmentation and caspase-3 activity were also attenuated by MMP-9 specific inhibitor. Four months after pilocarpine-induced SE, MFS was evident in vehicle-treated mice; in contrast, MFS was barely observed in MMP-9 specific inhibitor-treated mice. CONCLUSIONS: This study suggests MMP-9 is associated with hippocampal cell death and MFS after pilocarpine-induced SE. Furthermore, the findings that MMP-9 specific inhibitor ameliorates cell death and MFS offers the possibility of MMP-9 specific hydroxamic inhibitor as novel therapeutic strategy to reduce hippocampal damage and epileptogenesis.

Expression of GABAAR?1 subunit in cortical region and hippocampal formation of rats with radiation-induced diffuse cortical dysplasia / 重庆医科大学学报

Objective:To correlate diffuse cortical dysplasia(DCD) epileptogenicity and the expression of GABAAR?1 in adult rat with DCD by ?-ray irradiated injury.Methods:To establish ?-ray-induced model of DCD in rat,and newborn Wistar rats were allowed to survive for 14~16 weeks before HE,Nissl Stain,Timm's histochemical method and SABC immunohistochemistry.We observed the structure of cortical regions and hippocampal formation with naked eyes and under a light microscope,and assessed the hippocampal mossy fiber sprouting after HE staining,Nissl staining and Timm's histochemical method.The comparisons between every two groups were performed with Nemenyi test.We observed the expression of GABAAR?1 subunit in cortical regions and hippocampal formation in the animal model and quantitatively analyzed using immunohistochemistry of GABAAR?1 subunit.Results:Normal rats and irradiated pregnant rats didn't have any seizure.F1 generation rats had seizure by chance.EEG showed no typical sharp waves,or spikes.In utero irradiation of fetal rats had served as an injury-based animal model of cortical dysplasia and neuronal heterotopia.Exposure of fetal rats to a single dose of ?-irradiation on embryonic day 17 resulted in microcephaly,diffuse cortical dysplasia,neuronal heterotopia,heterotopic neurons in the hippocampus,and hypoplasia of the corpus callosum.The mossy fiber sprouted in hippocampi CA3 area bilaterally,however there was no mossy fiber sprouting in controls or irradiated rats(P

The Effect of MK 801 on the Development of Brain Damage, Spontaneous Recurrent Seizures and Mossy Fiber Sprouting in the Pilocarpine Induced Status Epilepticus Animal Model / 대한소아신경학회지

PURPOSE: We investigated the effect on MK 801 on the development on brain damage, spontaneous recurrent seizures and mossy fiber sprouting in the pilocarpine induced status epilepticus animal model. Methods: Fifty two adult Sprague Dawley male rats(180-240gm) were studied under ketamine/xylazine(87mg/13mg/kg, IP) anesthesia and were implanted at the F3, P3, F4, P4 areas for recording EEG. With a single intraperitoneal(IP) administration of pilocarpine hydrochloride(360mg/kg), 70% developed status epilepticus(SE). When SE was not induced within 1 hour after injection of pilocarpine, the second dose of pilocarpine(175mg/kg, IP) was injected, with 86.6% of success. Results: All studied animals were divided into two large groups, one group was treated with NMDA receptor antagonist, the other was control group. The mean duration of SE was 62.00+/-6.80 minutes in the MK 801(1mg/kg, IP, 30 minutes after SE) treated group, and 61.10+/-7.37 minutes in the control group without any signigicant differences(P>0.05). Neuronal loss(necrosis dominantly) was observed at CA1 and CA3 areas in the control group, with more loss after 6 weeks than 24 or 72 hrs specimens. However, there was no neuronal loss in MK 801 treated group. The protective effect of MK 801 for neuronal injury suggested the glutamate receptor activation was involved in the neuronal injury induced by repeated seizure attack. Spontaneous recurrent seizures(SRS) were observed 70% of animals in the control group, but there were no SRS observed in the MK 801 treated group. The mean scores of mossy fiber sprouting were significantly higher in the control group(2.05+/-0.47) than MK 801 treated group(0.4+/-0.32)(P<0.05). Conclusion: These results suggested that SRS and mossy fiber sprouting were associated with NMDA receptor activation, and NMDA receptor activation had a key role in the epilepsy development.

Observation on the Hippocampal Mossy Fiber Sprouting After Hypoxic-Ischemic Neuronal Loss in Juvenile and Mature Rat Brain / 대한소아신경학회지

PURPOSE: Reorganization of mossy fiber terminals in the supragranular layer of the dentate has been found in hippocampi of human epileptics and animal models by Timm staining. Many studies have provided evidence that mossy fiber sprouting is strongly associated with neuronal loss. But the question of whether cell loss is necessary for stimulation of mossy fiber sprouting is remained to be answered. In this present study, we evaluated whether hippocampal mossy fiber sprouting is induced in damaged hippocampus of the rats exposed to hypoxic-ischemic insults in juvenile and adult period. METHODS: At ages of 4-5 weeks and 2 months, the experimental rats were received procedure of right carotid artery unilateral ligation under anesthesia. After 3 hours of the recovery period, they were placed in an airtight 2000ml chamber and exposed to a 8% oxygen-92% nitrogen mixture delivered at 5 liter/min for 90 minutes (juvenile) and 50 minutes (adult). After the recovery period, The animals were returned to cages and housed with controls. 2 weeks later, rats of the control and hypoxic-ischemia group were anesthetised and then perfused with sodium sulfide solusion and fixed. 40micrometer (for Timm stain) and 5micrometer (for H & E stain) coronary brain sections were obtained, stained with Timm method and H < E stain for the observation of the neuronal loss and supragranular Timm granules in the hippocampi. RESULTS: Light microscopic examination of the brains from hypoxic-ischemic animals demonstrated ischemic changes of variable degrees in the hippocampal hilar and pyramidal cell layers. No supragranular mossy fiber sprouting were found in hippocampi of juvenile and adult rats with hypoxic-ischemic damages. CONCLUSION: These results implicated that hippocampal mossy fiber sprouting is not induced in the experimental hypoxic-ischemic encephalopathy of juvenile and adult rats, although cellular loss is found in hippocampus. Neuronal loss might be not necessary for the development of mossy fiber sprouting.

Mossy fiber Synaptic Reorganization and the Pattern of Sprouting in the Pilocarpine Epilepsy Model

BACKGROUND: The purpose of this study is to evaluate the synaptic reorganization and pattern of mossy fiber sprouting as a pathologic mechanism of chronic seizure in pilocarpine epilepsy model through histological alterations of hippocampus. METHOD: Sprague-Dawley, a sensitively damaged by pilocarpine stimulation, served as a experimental group(n=20). And the same dose of saline injected rats were served as a control group(n=10). They were implanted depth electrode in the hippocampus by a stereotaxic surgery, and injected pilocarpine 300mg/Kg intraperitoneally. They produced status epilepticus and the survival rats were monitored by a video-EEG monitoring system whether the spontaneous recurrent seizures occurring for more than 4 weeks. If more than 3 times spontaneous recurrent seizures were identified, then the rat hippocampus was examined by light microscope. RESULT: The pilocarpine injected group produced acute limbic seizure and developed to status epilepticus. The survival rats(n=10) became to chronic epilepsy state after silent period of everage 16.5 days. H&E staining demonstrated that loss of hilar polymorphic cell with ischemic changes and destruction of CA1 with damages of pyramidal cells in hippocampal subfields. Timm stains showed mossy fiber synatic reorganization in the supragranular and intragranular layer of dentate gyrus and infrapyramidal layer of CA3 hippocampal subfieid in pilocarpine induce seizure rats. CONCLUSION: These results suggest that chronic seizures in the pilocarpine epilepsy model is largely due to mossy fiber synatic reorganization, a consequence of supragranular mossy fiber sprouting. But intragranular and infrapyramidal axonal sprouting might have parts of role in synaptic reorganization. Additional research is required to determine the various patterns of axonal sprouting.

Synaptic Reorganization of Dentate Mossy Fibers and Expression of Calcium Binding Proteins in Hippocampal Sclerosis of Temporal Lobe Epilepsy

This study was designed to identify expression of calcium-binding proteins and synaptic reorganizations of dentate mossy fibers in hippocampal sclerosis of human temporal lobe epilepsy. Hippocampal neuronal density was quantitively analyzed in temporal lobe epilepsy group (n=50) to investigate the degree of hippocampal sclerosis and it was compared with that of autopsy control (n=3). To verify the distribution of calcium-binding proteins in neurons of epileptic hippocampi, the parvalbumin (PV)-immunoreactive and calbindin-D28K (CB)-immunoreactive neurons were quantitively analyzed in each area of Ammon's horn by immunohistochemical stain. Also, to clarify synaptic reorganizations of the dentate mossy fibers, a part of each hippocampus was examined under light microscopy and transmission electron microscopy using Timm sulphide silver method. In epileptic hippocampi, severity of hippocampal sclerosis (HS) was graded four, which consisted of 3 cases with no HS, 6 mild HS, 12 moderate HS, and 29 severe HS. The hippocampal neuronal loss was most prominent in CA1, followed by CA4 and CA2. Expression of calcium-binding proteins was more prevalent in CA2 of all groups. The proportion of PV-immunoreactive neurons in CA1 and CA4 significantly increased in the moderate and severe HS group, whereas the proportion of CB-immunoreactive neurons did not correlated with the severity of HS. Timm granules were noted in inner molecular supragranular layer of dentate gyrus of epileptic hippocampi and they tended to increase in proportion along with the severity of hippocampal sclerosis. Transmission electron microscopy showed that supragranular Timm granules corresponded to synaptic terminals of mossy fibers. These results suggest that parvalbumin appears to have more protective effect against neuronal loss and that mossy fiber synaptic reorganization seems to play a major role in pathogenesis of hippocampal sclerosis of human temporal lobe epilepsy.

A Morphological Study of Synaptic Reorganization in Mossy Fibers of the Dentate Gyrus according to Hippocampal Sclerosis in Temporal Lobe Epilepsy: A Comparison of Intraoperative ECoG Findings for Tailored Resection

This study was carried out to identify synaptic reorganization by mossy fibers of epileptic dentate gyrus by Timm sulphide silver histochemistry and to investigate degree of synaptic reorganization according to both hippocampal sclerosis and epileptiform discharge in human temporal lobe epilepsy(TLE). The control group was composed of two hippocampal tissues obtained from autopsied brain without neurological abnormalities. TLE group was composed of thirteen hippocampal tissues obtained from surgically resected temporal lobe. Among thirteen hippocampal tissues, five specimens were obtained both of two areas of each hippocampus with or without prominent epileptiform discharges on electrocorticogram(ECoG) for tailored hippocampal resection. Hippocampal cell density was quantitatively analyzed in TLE group and compared with that of control group. A portion of hippocampal tissue was observed under light microscopic and transmission electron microscopes after development with Danscher method. The results were as follows : Hippocampal cell loss was noted in all TLE group. Hippocampal cell loss greater than 30% of control values was found in 12 cases and average hippocampal cell loss was 70%(range 39-88%). The remaining 1 case had 13% hippocampal cell loss. The supragranular Timm granules were noted in inner molecular layer of dentate gyrus and tended to significantly increase in proportion as severity of hippocampal sclerosis. Average of hippocampal cell loss in two areas of five hippocampal tissues with or without prominent epileptiform discharge on ECoG was 73.6%(range 53-90%) and 66.4%(range 50-86%), which showed statistically significant (p<0.05) difference between these two areas and the supragranular Timm granules also tended to increase in the hippocampal tissue with epileptiform discharge. On transmission electron microscope, there showed distinct supragranular Timm granules correspond to mossy fiber synaptic terminals. The results of this study demonstrated that mossy fiber synaptic reorganization seems to play a major role in pathogenesis of human TLE and the development of mossy fiber synaptic reorganization is closely related to severity of hippocampal sclerosis. The result also support the rationale for tailoring the extent of hippocampal resection by intraoperative acute recording(ECoG) according to individual pathophysiology.

Expression of c-Fos Protein and Character of Mossy Fiber Sprouting in Hippocampus of Rat with Febrile Seizures / 实用儿科临床杂志

Objective To explore the expression of c-Fos protein and character of mossy fiber sprouting(MFS) in hippocampus of rat with febrile seizures(FS).Methods Thirty-six 21-day-old male Sprague-Dawley rats were randomly divided into FS group,febrile control(FG) group and normal control(NG) group.FS was established by hyperthermal bath.Immune histochemistry and(Timm′s) staining were used to examine the expression of c-Fos protein in CA1 region and MFS in CA3 region of hippocampus.Results Excessive expression of c-Fos protein presented in the hippocampal CA1 region of FS group.The surface area percentage of c-Fos protein of FS group[(2.26?0.23)%] was higher than that of FG group[(1.08?0.19)%] and NG group[(0.71?0.14)%],there were significant difference between FS group and the other two groups(?~2=10.48 P

Morphologic changes of hippocampal formation in rat of kainate-induced temporal lobe epilepsy / 第三军医大学学报

Objective To study the pathologic changes of hippocampus during the model development and explore the mechanism of epileptogenesis by observing the morphologic changes of hippocampal formation in rat of kainate-induced chronic temporal lobe epilepsy (TLE). Methods Thirty Wistar rats were injected of Kainic acid at dose of 2 ?g/20 ?l into the lateral cerebral ventricle under the guidence of stereotactic technique to make a epileptic focus, and subgrouped under acute phase, silent period and chronic phase. Another 10 rats received normal saline as controls. The rats were killed at 1 day, 15 day and 6 months after epileptic model establishment, and the hippocampus was taken out for HE staining, TUNEL staining, Timm’s staining, NSE staining. Results By cell counting, the neuron loss mainly occurred in acute phase, worst in CA3 and CA4, moderate in CA1 and CA2, and no loss in the dentate gyrus. The cell apoptosis in hippocampal structure was detected by TUNEL staining. Timm’s staining showed that mossy fiber began sprouting in silent period and increased continuously. Conclusion The morphologic changes of hippocampal formation in rat of kainate-induced TLE is mainly the neuron loss and the glia hyperplasy.