Angiotensin II and its receptor in activated microglia enhanced neuronal loss and cognitive impairment following pilocarpine-induced status epilepticus.
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.
Department of Neurology, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China. Electronic address: sunhongxjt@163.com.
Hong
H
Sun
Department of Neurology, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China. Electronic address: whq60@163.com.
HaiQin
H
Wu
Department of Neurology, People's Liberation Army 401 Hospital, Qingdao, Shandong 266071, China.
Xin
X
Yu
Department of Neurology, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
GuiLian
G
Zhang
Department of Neurology, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
Ru
R
Zhang
Department of Neurology, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
ShuQin
S
Zhan
Department of Neurology, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
HuQing
H
Wang
Department of Neurology, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
Ning
N
Bu
Department of Neurology, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
XiaoLing
X
Ma
Department of Neurology, The Fourth Affiliated Hospital, Harbin Medical University, Harbin 150001, Heilongjiang Province, China.
YongNan
Y
Li
D000804:Angiotensin II / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019808:Losartan / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism*; D013226:Status Epilepticus / Q000150:complications / Q000378:metabolism* / Q000473:pathology
D047228:Angiotensin II Type 1 Receptor Blockers; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; D019808:Losartan
AII; Cognitive impairment; Epilepsy; Losartan; Microglia; Neuronal loss