Neuroprotective Effects of Acetylsalicylic Acid in Middle Cerebral Artery Occlusion-Induced Brain Ischemia in Rats: Suppression of iNOS, HIF-1α, TNF-α, and Active Caspase-3 Expression

Acetylsalicylic acid (ASA) is neuroprotective through various pharmacological action sites. The aim of this study was to examine the detailed mechanisms underlying the inhibitory effect of ASA in inflammatory and apoptotic responses induced by middle cerebral artery occlusion (MCAO) in rats. In this study, ASA significantly attenuated MCAO-induced focal cerebral ischemia in rats. Administration of ASA at 10-20 mg/kg showed marked reductions in infarct size compared with that of control rats. MCAO-induced focal cerebral ischemia was associated with increases in iNOS, HIF-1α, active caspase-3, and TNF-α mRNA expressions in ischemic regions. These expressions were markedly inhibited by treatment with ASA (20 mg/kg). In conclusion, the neuroprotective effect of ASA may mediate at least a portion of the inhibition of HIF-1α and TNF-α activations, followed by inhibition of apoptosis formation (active caspase-3) and inflammatory response (iNOS), resulting in a reduction in the infarct volume in ischemia-reperfusion brain injury. Thus, ASA treatment may represent an ideal approach to lowering the risk of or improving function in ischemia-reperfusion brain injury-related disorders.