Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038220 (status epilepticus)
 7,272 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Astrocytes are relatively resistant to injury compared to neurons and oligodendrocytes. Here, we report transient region-specific loss of astrocytes in mice early after pilocarpine-induced status epilepticus (SE). In the dentate hilus, immunoreactivity for glial acidic fibrillary protein (GFAP) was decreased, and the number of healthy appearing GFAP- or S100beta-positive cells was significantly reduced (> or =65%) 1 and 3 days after pilocarpine-induced SE. Many remaining GFAP-positive cells were shrunken, and 1 day after SE electron microscopy revealed numerous electron-dense degenerating astrocyte processes and degenerating glial somata in the hilus. Degeneration of GFAP-expressing cells may be linked to hilar neuronal death, because we did not observe loss of astrocytes after kainate-induced SE, after which hilar neurons remained intact. Ten days after SE, hilar GFAP immunoreactivity had returned, partially from GFAP-positive cells in the hilus. Unlike control mice, many GFAP-positive hilar processes originated from cell bodies located in the subgranular zone (SGZ). To investigate whether proliferation contributes to hilar repopulation, we injected 5-bromo-2'-deoxyuridine (BrdU) 3 days after SE. Five hours later and up to 31 days after SE, many BrdU/GFAP colabeled cells were found in the hilus and the SGZ, some with hilar processes, indicating that proliferation in both areas contributes to generation of hilar astrocytes and astrocyte processes. In contrast to pilocarpine-induced SE in mice, astrocyte degeneration was not found after pilocarpine-induced SE in rats. These findings demonstrate astrocyte degeneration in the mouse dentate hilus specifically in the mouse pilocarpine epilepsy model, followed by astrogenesis leading to hilar repopulation.
 ...
PMID:Degeneration and proliferation of astrocytes in the mouse dentate gyrus after pilocarpine-induced status epilepticus. 1679 40

Epilepsy is a common disease of the central nervous system. This study aimed to investigate the role of mitochondrial Rho (Miro) 1 in epilepsy, using a mouse model of pilocarpine-induced status epilepticus (SE). Intraperitoneal injection of pilocarpine induced epileptic seizures in mice and significantly decreased Miro 1 expression in the hippocampus. Moreover, pilocarpine treatment increased the serum levels of heat shock protein 70 (HSP70) and S100 calcium binding protein B (S100B) and led to hippocampal neuronal injury and apoptosis. The intrinsic apoptotic pathway was activated in the hippocampal neurons following pilocarpine-induced SE, as evidenced by increased levels of cleaved caspase-3 and Bax, downregulation of Bcl-2, and the release of cytochrome c from mitochondria to cytoplasm. By contrast, forced expression of Miro 1 by lateral ventricular administration of adenovirus mitigated pilocarpine-induced epileptic seizures, reduced the elevation of HSP70 and S100B, and inhibited hippocampal neuronal apoptosis by suppressing the intrinsic apoptotic pathway. In summary, our data demonstrates that ectopic expression of Miro 1 alleviated pilocarpine-induced SE and protected hippocampal neurons by inhibiting the intrinsic apoptotic pathway. These findings provide new insights into epileptic disorders and suggest a potential neuroprotective value of Miro 1 in the treatment of epilepsy.
 ...
PMID:Ectopic expression of Miro 1 ameliorates seizures and inhibits hippocampal neurodegeneration in a mouse model of pilocarpine epilepsy. 2936 85

Status epilepticus is a condition resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms that lead to abnormally prolonged seizures and require urgent administration of antiepileptic drugs. Refractory status epilepticus requires anesthetics drugs and may lead to brain injury with molecular and cellular alterations (eg, inflammation, and neuronal and astroglial injury) that could induce neurologic sequels and further development of epilepsy. Outcome scores based on demographic, clinical, and electroencephalography (EEG) condition are available, allowing prediction of the risk of mortality, but the severity of brain injury in survivors is poorly evaluated. New biomarkers are needed to predict with higher accuracy the outcome of patients admitted with status in an intensive care unit. Here, we summarize the findings of studies from patients and animal models of status epilepticus. Specific protein markers can be detected in the cerebrospinal fluid and the blood. One of the first described markers of neuronal death is the neuron-specific enolase. Gliosis resulting from inflammatory responses after status can be detected through the increase of S100-beta, or some cytokines, like the High Mobility Group Box 1. Other proteins, like progranulin may reflect the neuroprotective mechanisms resulting from the brain adaptation to excitotoxicity. These new biomarkers aim to prospectively identify the severity and development of disability, and subsequent epilepsy of patients with status. We discuss the advantages and disadvantages of each biomarker, by evaluating their brain specificity, stability in the fluids, and sensitivity to external interferences, such as hemolysis. Finally, we emphasize the need for further development and validation of such biomarkers in order to better assess patients with severe status epilepticus.
 ...
PMID:Cerebrospinal fluid and blood biomarkers of status epilepticus. 3182 92