Epilepsy is a brain condition characterized by the recurrence of unprovoked seizures. Recent studies have shown that complement component 3 (C3) aggravate the neuronal injury in epilepsy. And our previous studies revealed that TRPV1 (transient receptor potential vanilloid type 1) is involved in epilepsy. Whether complement C3 regulation of neuronal injury is related to the activation of TRPV1 during epilepsy is not fully understood. We found that in a mouse model of status epilepticus (SE), complement C3 derived from astrocytes was increased and aggravated neuronal injury, and that TRPV1-knockout rescued neurons from the injury induced by complement C3. Circular RNAs are abundant in the brain, and the reduction of circRad52 caused by complement C3 promoted the expression of TRPV1 and exacerbated neuronal injury. Mechanistically, disorders of neuron-glia interaction mediated by the C3-TRPV1 signaling pathway may be important for the induction of neuronal injury. This study provides support for the hypothesis that the C3-TRPV1 pathway is involved in the prevention and treatment of neuronal injury and cognitive disorders.
Animals ; Astrocytes/metabolism* ; Complement C3/metabolism* ; Epilepsy ; Mice ; Neurons/pathology* ; Status Epilepticus ; TRPV Cation Channels/metabolism*

OBJECTIVETo investigate the characteristics of microglial activation of hippocampus in experimental epileptic rats.

METHODSMorphological changes and proliferation of OX-42 positive cells were compared at different time points after status of epilepticus (SE) in lithium-pilocarpine induced epileptic rats.

RESULTSOX-42 positive cells were activated after SE, which increased to a peak at 3-7 d and in a relatively stable state at 7-14 d; then gradually decreased after 14d and returned to slightly higher level than previously at 21 d.

CONCLUSIONInflammatory injury, microglial activation and cell proliferation are closely related after seizures, microglial activation may be an important mechanism in the inflammatory injury of epilepsy.

Animals ; Cell Proliferation ; Disease Models, Animal ; Hippocampus ; cytology ; pathology ; Male ; Microglia ; pathology ; Rats ; Rats, Sprague-Dawley ; Status Epilepticus ; pathology

Adolescent ; Adult ; Anesthetics, Intravenous ; Electroencephalography ; Female ; Humans ; Hypothermia, Induced ; methods ; Male ; Prospective Studies ; Status Epilepticus ; pathology ; therapy ; Young Adult

Anticonvulsants ; therapeutic use ; Brain ; pathology ; physiopathology ; Brain Waves ; physiology ; Child ; Electroencephalography ; Humans ; Landau-Kleffner Syndrome ; physiopathology ; Sleep ; physiology ; Sleep Stages ; physiology ; Status Epilepticus ; epidemiology ; etiology ; physiopathology ; therapy

Temporal lobe epilepsy (TLE) is a common and severe neurological disorder which is often intractable. It can not only damage the normal structure and function of hippocampus, but also affect the neurogenesis in dentate gyrus (DG). It is well documented from researches on the animal models of TLE that after a latent period of several days, prolonged seizure activity leads to a dramatic increase in mitotic activity in the hippocampal DG. However, cell proliferation returns to baseline levels within 3-4 weeks after status epilepticus (SE). Meanwhile, there are two major abnormalities of DG neurogenesis, including the formation of hilar basal dendrites and the ectopic migration of newborn granule cells into the polymorphic cell layer, which may affect epileptogenesis and seizure onset. However, the specific contribution of these abnormalities to seizures is still unknown. In other words, whether they are anti-epileptic or pro-epileptic is still under heated discussion. This article systematically reviews current knowledge on neurogenesis and epilepsy based on the results of studies in recent years and discusses the possible roles of neurogenesis in epileptogenesis and pathologic mechanisms, so as to provide information for the potential application of neurogenesis as a new clinical therapeutic target for temporal lobe epilepsy.
Animals ; Brain ; Cell Movement ; physiology ; Cell Proliferation ; physiology ; Dendrites ; pathology ; Dentate Gyrus ; growth & development ; pathology ; Epilepsy, Temporal Lobe ; etiology ; pathology ; physiopathology ; Hippocampus ; growth & development ; pathology ; Humans ; Mitosis ; physiology ; Neurogenesis ; physiology ; Neurons ; pathology ; Seizures ; etiology ; physiopathology ; Status Epilepticus ; physiopathology

OBJECTIVE: To investigate the role of neuropeptide Y(NPY) positive interneurons in the generation and compensation of temporal lobe epilepsy. METHODS: Pilocarpine-induced rat model was founded. Immunohistochemistry was used to observe the number changes and axonal sprouting of NPY interneurons at different time points in the hippocampus of rats. RESULTS: After lithium-chloride and pilocarpine administration, 92.9% rats were induced status epilepticus (SE) successfully, and the mortality rate was 19.2%. In the experimental group, the number of NPY positive neurons decreased in the hilus of the hippocampus, and was least on 7 d after the SE (P<0.01). In the chronic phase, the number of hilus NPY neurons partially recovered, but was still less than the number in the control group on 60 d after the SE (P<0.05). No evident changes of the number of NPY neurons existed in CA domains (P>0.05) except the loss of them in CA3 area on 7 d after the SE (P>0.05). Increased NPY positive fibers could be seen in the molecular layer of the dentate gyrus on 30 d after the SE. CONCLUSION NPY interneurons have different sensitivities to the injuries induced by seizures at different time points and domains. Loss of NPY interneurons plays an important role in the generation of temporal lobe epilepsy, while axonal sprouting of them may play a significant role in the compensation of temporal lobe epilepsy.
Animals ; Epilepsy, Temporal Lobe ; chemically induced ; pathology ; Hippocampus ; metabolism ; pathology ; Interneurons ; metabolism ; pathology ; Male ; Neuropeptide Y ; metabolism ; Pilocarpine ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Retrograde Degeneration ; pathology ; Status Epilepticus ; chemically induced ; pathology

OBJECTIVENeurogenesis in the dentate gyrus of hippocampus persists in brain of the immature and adult mammalian including human and it can be regulated by physiological and pathological events including nutritional status and seizures. The present study was designed to investigate the potential effects of malnutrition followed by status epileptics on hippocampal neurogenesis in the immature rat.

METHODSRat pups were divided into 4 groups: malnourished (M), nourished (N), malnourished plus seizures (MS) and nourished plus seizures (NS). The rat pups of group M and group MS were maintained on a starvation regimen from postnatal day 2 (P2) to P18. The status epilepticus of the rat pups in group MS and group NS was elicited by unilateral microinfusion of kainic acid (KA) into the amygdula at P15. Rat pups of the 4 groups were given bromodeoxyuridine (BrdU) intraperitoneally twice daily for 2 days beginning at P17. At P19, the rat pups were killed and the brains were processed for BrdU mitotic labeling combined with double-label immunohistochemistry using early neuron- or glia-specific markers TuJ1 (beta III tubulin) or GFAP (glial fibrillary acidic protein).

RESULTSThere were no significant differences in the latent time of seizure between group M and group N [(12.4 +/- 2.6) min vs. (12.1 +/- 2.9) min, P < 0.05]. Histological assessment did not reveal any evidence of hippocampal cell loss after status epilepticus in either group. BrdU-labeled cells were significantly higher in the rats of group MS (374 +/- 18) than group M (303 +/- 20), group NS (312 +/- 24) than group N (269 +/- 18), respectively (P < 0.01). There was also significant difference between group M and group N, group MS and group NS, respectively (P < 0.01). No significant difference was seen between the rats of group NS and group M (P > 0.05). Approximately 60% of BrdU-labeled cells coexpressed TuJ1, and 5% approximately 10% of those co-expressed GFAP.

CONCLUSIONEarly malnutrition do not alter KA seizure susceptibility and the behavioral manifestations of seizures at P15. Although malnutrition and status epilepticus can increase the proliferation of newly developed cells in the immature rat respectively, malnutrition followed by status epilepticus further increases this proliferation. Furthermore, most of newly developed cells differentiate into early neurons.

Animals ; Animals, Newborn ; Body Weight ; Bromodeoxyuridine ; metabolism ; Glial Fibrillary Acidic Protein ; analysis ; Hippocampus ; chemistry ; pathology ; Immunohistochemistry ; Malnutrition ; pathology ; Neurons ; chemistry ; pathology ; Rats ; Rats, Wistar ; Status Epilepticus ; chemically induced ; pathology ; Tubulin ; analysis

We report on a 55-year-old man with alcoholic liver cirrhosis who presented with status epilepticus. Laboratory analysis showed markedly elevated blood ammonia. Brain magnetic resonance imaging (MRI) showed widespread cortical signal changes with restricted diffusion, involving both temporo-fronto-parietal cortex, while the perirolandic regions and occipital cortex were uniquely spared. A follow-up brain MRI demonstrated diffuse cortical atrophy with increased signals on T1-weighted images in both the basal ganglia and temporal lobe cortex, representing cortical laminar necrosis. We suggest that the brain lesions, in our case, represent a consequence of toxic effect of ammonia.
Ammonia/blood ; Atrophy/pathology ; Brain Diseases/blood/*diagnosis/*etiology ; Hepatic Encephalopathy/*complications ; Humans ; Liver Cirrhosis, Alcoholic/*complications ; Magnetic Resonance Imaging/*methods ; Male ; Middle Aged ; Necrosis/pathology ; Status Epilepticus/pathology

OBJECTIVETo study the possible protection of edaravone on neurons of the hippocampus after status convulsion (SC) and its effects on the expression of interleukin-1beta (IL-lbeta) in juvenile rats.

METHODSOne hundred and ninety-five juvenile male Sprague-Dawley rats were randomly divided into three groups: SC, edaravone pretreatment and normal saline control (control group). Each group was subdivided into five groups sacrificed at 4, 12, 24, 48 and 72 hrs after SC induction. SC model was prepared using lithium-pilocarpine. The edaravone pretreatment group received edaravone by intraperitoneal injection once daily three days before convulsion induction. Histopathologic changes in the hippocampus were viewed under a light microscope and an electron microscope. Expression of apoptosis cells was observed by TdT-mediated dUTP nick end labeling (TUNEL). Expression of IL-lbeta protein was determined by immunohistochemistry.

RESULTSUnder the electron microscrope, a small quantity of neurons showed karyopycnosis and endocytoplasmic reticulum (ER) expanded remarkably 24 hrs after SC induction; at 48 hrs the ER expanding was alleviated somewhat but mitochomdria swelling was more severe. The edaravone pretreatment group showed less severe neuronal changes compared with the SC group under the microscopes. The TUNEL positive cells in the hippocampus of the SC group were significantly more than those of the control group 12 hrs, and peaked at 48 hrs after SC induction. The edaravone pretreatment group showed decreased TUNEL positive cells in the hippocampus compared with the SC group, although the positive cells were more than those in the control group between 12 and 48 hrs after SC induction. The immunohistochemistry assay demonstrated that the expression of IL-lbeta in the hippocampus of the SC group increased significantly compared with that of the control group 12, 24, 48 and 72 hrs after SC induction. Edaravone pretreatment resulted in a significantly decreased IL-lbeta expression in the hippocampus as compared with the SC group.

CONCLUSIONSEdaravone pretreatment may decrease the IL-1beta expression and neuronal apoptosis in the hippocampus. This suggests that edaravone may have protective effects against the hippocampal damage caused by SC.

Animals ; Antipyrine ; analogs & derivatives ; pharmacology ; Hippocampus ; chemistry ; drug effects ; pathology ; ultrastructure ; Immunohistochemistry ; In Situ Nick-End Labeling ; Interleukin-1beta ; analysis ; Male ; Neurons ; drug effects ; Neuroprotective Agents ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Status Epilepticus ; drug therapy ; metabolism ; pathology

BACKGROUND: Several growth factors, including growth hormone (GH) and Insulin like growth factor-I, have been reported to have a neuroprotective effect in experimental models of hypoxic ischemia. This study is aimed at assessing the clinical significance of growth hormone for neuroprotection in status epilepticus induced neuronal cell deaths. METHODS: Pilocarpine induced status epilepticus (SE) was studied in rats (male, Sprague-Dawley). Rats were divided into pre- or post-treatment groups that had either a low (5 U/kg/day) or high (10 U/kg/day) dose of recombinant human GH (Eutropin, LGCI, Korea), and then subdivided into 24 hour, 72 hour and 1 week groups. This was done in the pretreatment groups for 5 days before SE and in the post-treatment groups for 5 days after 2 hrs of SE injection, after SE, the GH was daily injected via intraperitoneal route. Status epilepticus was induced by pilocarpine (360 mg/kg) with scoplamine (1 mg/kg) 30 minutes before pilocarpine injection using a stereotaxic instrument and EEG monitoring. Rats were killed at 24 and 72 hours after the SE in the pretreatment groups and at 1 week after the SE in the post-treatment groups for pathology studies. Neuronal injuries in the rat brain were studied by Hematoxylin & Eosin stain and the TUNEL method. RESULTS: Neuronal necrosis was found in the hippocampal CA1 and CA3 regions in all experimenatal groups after SE, and was more severe in the CA3 region. Apoptosis was found only in the pre-GH treated group and there were TUNEL-positive and morphologically necrotic cells in the hippocampal CA1 and CA3 regions at 72 hours after SE. Neuronal necrosis and apoptosis were significantly decreased in the high dose GH treated groups (p<0.05) compare to controlsd, but not in the low dose GH hormone treated groups (p>0.05). CONCLUSION: Growth hormone has a neuroprotective effect in neuronal cell death (necrosis and apoptosis) that is caused by pilocarpine induced status epilepticus in a dose dependent manner and prevents the activation of apoptosis by SE in neurons which eventually become necrotic.
Animals ; Apoptosis ; Brain* ; Cell Death ; Electroencephalography ; Eosine Yellowish-(YS) ; Growth Hormone* ; Hematoxylin ; Humans ; In Situ Nick-End Labeling ; Insulin ; Intercellular Signaling Peptides and Proteins ; Ischemia ; Models, Theoretical ; Necrosis ; Neurons* ; Neuroprotective Agents* ; Pathology ; Pilocarpine* ; Rats ; Status Epilepticus*