Losartan inhibits development of spontaneous recurrent seizures by preventing astrocyte activation and attenuating blood-brain barrier permeability following pilocarpine-induced status epilepticus.
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.
['Hong|Sun|S|', 'JianCheng|He|H|', 'JiaWen|Wu|W|', 'ShuQin|Zhan|Z|', 'GuiLian|Zhang|Z|', 'HaiQin|Wu|W|', 'Ru|Zhang|Z|', 'Zhen|Gao|G|', 'HongWei|Ren|R|']
D000818:Animals D001253:Astrocytes D001812:Blood-Brain Barrier D001921:Brain D004195:Disease Models, Animal D004827:Epilepsy D019808:Losartan D008297:Male D055495:Neurogenesis D009474:Neurons D018696:Neuroprotective Agents D010539:Permeability D051381:Rats D017207:Rats, Sprague-Dawley D012640:Seizures D013226:Status Epilepticus
Losartan Astrocyte activation Blood-brain barrier Epilepsy AQP4