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

Neuroinflammation plays a role in the pathology of epilepsy and in cognitive impairment. Angiotensin II (AII) and the angiotensin receptor type 1 (AT1) have been shown to regulate seizure susceptibility in different models of epilepsy. Inhibition of AT1 attenuates neuroinflammatory responses in different neurological diseases. In the present study, we showed that the protein expression of AII and AT1 was increased in activated microglia following lithium pilocarpine-induced status epilepticus (SE) in rats. Furthermore, the AT1 receptor antagonist, losartan, significantly inhibited SE-induced cognitive impairment and microglia-mediated inflammation. Losartan also prevented SE induced neuronal loss in the hippocampus and exerted neuroprotection. These data suggest that losartan improves SE-induced cognitive impairment by suppressing microglia mediated inflammatory responses and attenuating hippocampal neuronal loss. Overall, our findings provide a possible therapeutic strategy for the treatment of cognitive impairment in epilepsy.
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PMID:Angiotensin II and its receptor in activated microglia enhanced neuronal loss and cognitive impairment following pilocarpine-induced status epilepticus. 2572 9

Blood-brain barrier (BBB) damage and astrocyte activation are important cause of recurrent epilepsy. There is experimental evidence for increased angiotensin receptor type 1 (AT1) expression during BBB breakdown and brain injury, and that blocking the AT1 receptor (e.g., with losartan) can improve microcirculation, attenuate inflammation and oxidative stress, and exhibit neuroprotective effects. Thus, in the present study, we examined the effects of losartan on status epilepticus-induced astrocyte activation and BBB damage in the lithium-pilocarpine model of epilepsy in rats. We found that losartan treatment reduced astrocyte activation and BBB damage. However, under physiological condition, losartan have not effect on BBB permeability and astrocyte activation. Further, losartan exhibited a direct antiepileptic effect, which was mediated, at least in part by normalizing AQP4 expression after SE. As the changes of AQP4 expression were closely related to astrocyte activation and BBB permeability, the antiepileptic action of losartan likely relates to its effects on astrocyte activation and BBB permeability. Overall, these data suggest that losartan may be a useful antiepileptic agent in the clinic, either alone or in combination with other antiepileptic drugs.
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PMID:Losartan inhibits development of spontaneous recurrent seizures by preventing astrocyte activation and attenuating blood-brain barrier permeability following pilocarpine-induced status epilepticus. 3107 74