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

Tsung Hao Chang, Chien Liang Liu, Kuang Hung Lin, Meng Nan Lin, George Hsiao, Joen Rong Sheu

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)793-799
Number of pages7
JournalPharmaceutical Biology
Volume46
Issue number10-11
DOIs
Publication statusPublished - Oct 2008

Keywords

  • Acetylsalicylic acid
  • Caspase-3
  • HIF-1α
  • iNOS
  • Middle cerebral artery occlusion
  • TNF-α

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Pharmaceutical Science
  • Complementary and alternative medicine
  • Molecular Medicine

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