pharmacological inhibition of perk attenuates early brain injury after subarachnoid hemorrhage in rats through the activ.药物抑制活跃变弱早期脑损伤大鼠蛛网膜下腔出血后通过一种蛋白激精品.pdfVIP

Mol Neurobiol DOI 10.1007/s12035-016-9790-9 Pharmacological Inhibition of PERK Attenuates Early Brain Injury After Subarachnoid Hemorrhage in Rats Through the Activation of Akt Feng Yan 1 Shenglong Cao 1 Jianru Li 1 Brandon Dixon 2 Xiaobo Yu 1 Jingyin Chen 1 Chi Gu 1 Wang Lin 1 Gao Chen 1 Received: 24 November 2015 /Accepted: 11 February 2016 # Springer Science+Business Media New York 2016 Abstract Neuronal apoptosis is a central pathological process caspase-3 expression and neuronal death, thereby improving in subarachnoid hemorrhage (SAH)-induced early brain inju- neurological deficits at 72 h after SAH. The selective Akt ry. Endoplasmic reticulum (ER) stress was reported to have a inhibitor MK2206 abolished the beneficial effects of vital role in the pathophysiology of neuronal apoptosis in the GSK2606414. PERK, the major transducer of ER stress, is brain. The present study was designed to investigate the po- involved in neuronal apoptosis after SAH. The inhibition of tential effects of ER stress and its downstream signals in early PERK reduces early brain injury via Akt-related anti-apopto- brain injury after SAH. One hundred thirty-four rats were sis pathways. PERK may serve as a promising target for future subjected to an endovascular perforation model of SAH. The therapeutic intervention. RNA-activated protein kinase-like ER kinase (PERK) inhibi- tor GSK2606414 and the Akt inhibitor MK2206 were injected Keywords Subarachnoid hemorrhage . Early brain injury . intracerebroventricularly. SAH grade, neurologic scores, and Endoplasmic reticulum stress . PERK . Apoptosis brain water content were measured 72 h after subarachnoid hemorrhage. Expression of PERK and its downstream signals, Akt, Bcl-2, Bax, and cleaved caspase-3, were examined using Introduction Western blot analy