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.