α‑lipoic acid protects against cerebral ischemia/reperfusion‑induced injury in rats

Deng,Houliang; Zuo,Xialin; Zhang,Jingjing; Liu,Xiaoxia; Liu,Li; Xu,Qian; Wu,Zhuomin; Ji,Aimin

doi:10.3892/mmr.2015.3170

α‑lipoic acid protects against cerebral ischemia/reperfusion‑induced injury in rats

Authors:
- Houliang Deng
- Xialin Zuo
- Jingjing Zhang
- Xiaoxia Liu
- Li Liu
- Qian Xu
- Zhuomin Wu
- Aimin Ji
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Affiliations: Center for Drug Research and Development, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, P.R. China, Institute of Neurosciences and The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510260, P.R. China
Published online on: January 9, 2015 https://doi.org/10.3892/mmr.2015.3170
Pages: 3659-3665

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Abstract

It is well established that the brain is sensitive to ischemia/reperfusion (I/R)‑induced injury. α‑lipoic acid (LA), a free radical scavenger and antioxidant, has a neuroprotective effect against cerebral I/R‑induced injury, however, the underlying mechanisms remain to be elucidated. Therefore, the present study was undertaken to evaluate whether LA was able to protect against cerebral I/R‑induced injury and to examine the potential mechanisms. The neuroprotective effects of LA were investigated in a rat model of transient focal ischemia induced by middle cerebral artery occlusion (MCAO) followed by reperfusion. Adult male Sprague‑Dawley rats were randomly assigned into the sham, cerebral I/R injury model and model plus LA groups. Cerebral I/R injury was induced by 90 min MCAO followed by reperfusion for 24 h. Cerebral infarct size was detected by 2,3,5‑triphenyltetrazolium chloride staining. Neurological deficit score (NDS), brain water content and oxidative parameters, including malondialdehyde (MDA), nitric oxide (NO), total antioxidant capacity (T‑AOC) and superoxide dismutase (SOD) were measured. The expression of cleaved caspase‑3, brain‑derived neurotrophic factor (BDNF), phosphatidylinositol‑4,5‑bisphosphate 3‑kinase (PI3K), p‑Akt and phosphorylated extracellular signal‑regulated kinase 1/2 (p‑ERK1/2) were also analyzed using western blotting. The present study demonstrated that pretreatment with LA significantly decreased the infarction size, brain water content and improved NDS. LA reversed the levels of oxidative parameters, including MDA, NO, T‑AOC and SOD to their normal state in rat brains following cerebral I/R. Furthermore, the expression of cleaved caspase‑3 markedly decreased and the expression of BDNF, PI3K, p‑Akt and p‑ERK1/2 significantly increased following administration of LA. On the basis of these findings, it was concluded that LA protected the brain from cerebral I/R damage by attenuation of oxidative stress and caspase‑dependent apoptosis. Furthermore, LA exerts its neuroprotective effects potentially through activation of the BDNF‑PI3K/Akt‑ERK1/2 pathway.

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