Angiotensin II and its receptor in activated microglia enhanced neuronal loss and cognitive impairment following pilocarpine-induced status epilepticus

Abstract

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.

Keywords: AII; Cognitive impairment; Epilepsy; Losartan; Microglia; Neuronal loss.