Statins Enhance Expression of Growth Factors and Activate the PI3K/Akt-mediated Signaling Pathway After Experimental Intracerebral Hemorrhage

Overview

Journal World J Neurosci

Date 2013 Mar 14

PMID 23482588

Citations 24

Authors

Dongmei Yang

Yuxia Han

Jianfeng Zhang

Michael Chopp

Donald M Seyfried

Affiliations

Soon will be listed here.

Abstract

Previous studies have demonstrates that statins improve neurological outcome and promote neurovascular recovery after ICH. This study is designed to examine whether simvastatin and atorvastatin affect levels of growth factors and activate the Akt signaling pathway during the recovery phase after intracerebral hemorrhage (ICH) in rats. Sixty (60) male Wistar rats were subjected to ICH by stereotactic injection of 100 μL of autologous blood into the striatum and were treated with or without simvastatin or atorvastatin. Neurological functional outcome was evaluated by behavioral tests (mNSS and corner turn test) at different time points after ICH. Brain extracts were utilized for Enzyme-linked immunosorbent assay (ELISA) analyses to measure vascular endothelial growth factor (VEGF); brain-derived neurotrophin factor (BDNF) expression, and nerve growth factor (NGF). Western blot was used to measure the changes in the Akt-mediated signaling pathway. Both the simvastatin- and atorvastatin-treated animals had significant neurological improvement at 2 weeks post-ICH. Simvastatin and atorvastatin treatment increased the expression of BDNF, VEGF and NGF in both low- and high-dose groups at 7 days after ICH ( < 0.05). Phosphorylation of Akt, glycogen synthase kinase-3β (GSK-3β), and cAMP response element-binding proteins (CREB) were also increased at 7 days after statin treatment. These results suggest that the therapeutic effects of statins after experimental ICH may be mediated by the transient induction of BDNF, VEGF and NGF expression and the activation of the Akt-mediated signaling pathway.

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