Neuroprotective potential of fasudil mesylate in brain ischemia-reperfusion injury of rats

Cell Mol Neurobiol. 2009 Mar;29(2):169-80. doi: 10.1007/s10571-008-9308-8. Epub 2008 Sep 11.


We previously reported that inhibition of Rho-kinase (ROCK) by hydroxyl fasudil improves cognitive deficit and neuronal damage in rats with chronic cerebral ischemia (Huang et al., Cell Mol Neurobiol 28:757-768, 2008). In this study, fasudil mesylate (FM) was investigated for its neuroprotective potential in rats with ischemia following middle cerebral artery occlusion (MCAO) and reperfusion. The effect of fasudil mesylate was also studied in rat brain cortical and hippocampal slices treated with oxygen-glucose deprivation (OGD) injury. Gross anatomy showed that cerebral infarct size, measured with 2,3,5-triphenyltetrazolium chloride (TTC) staining, was significantly smaller in the FM-treated than in the non-FM-treated ischemic rats. In the brain regions vulnerable to ischemia of ischemic rats, fasudil mesylate was also found to significantly restore the enzyme protein expression level of endothelial nitric oxide synthase (eNOS), which was decreased in ischemia. However, it remarkably reduced the protein synthesis of inducible nitric oxide synthase (iNOS) that was induced by ischemia and reperfusion. In rat brain slices treated with OGD injury, fasudil mesylate increased the neuronal cell viability by 40% for cortex and by 61% for hippocampus, respectively. Finally, in the presence of OGD and fasudil mesylate, superoxide dismutase (SOD) activity was increased by 50% for cortex and by 58% for hippocampus, compared to OGD only group. In conclusion, our in vivo study showed that fasudil mesylate not only decreased neurological deficit but also reduced cerebral infarct size, possibly and at least partially by augmenting eNOS protein expression and inhibiting iNOS protein expression after ischemia-reperfusion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / analogs & derivatives*
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / pharmacology
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / therapeutic use
  • Animals
  • Calcium Channel Blockers / pharmacology
  • Calcium Channel Blockers / therapeutic use
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / physiopathology
  • Disease Models, Animal
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Hippocampus / physiopathology
  • Hypoxia-Ischemia, Brain / drug therapy*
  • Hypoxia-Ischemia, Brain / metabolism
  • Hypoxia-Ischemia, Brain / physiopathology
  • Infarction, Middle Cerebral Artery / drug therapy
  • Infarction, Middle Cerebral Artery / metabolism
  • Infarction, Middle Cerebral Artery / physiopathology
  • Male
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / therapeutic use
  • Nitric Oxide Synthase Type II / drug effects
  • Nitric Oxide Synthase Type II / metabolism
  • Nitric Oxide Synthase Type III / drug effects
  • Nitric Oxide Synthase Type III / metabolism
  • Organ Culture Techniques
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / physiopathology
  • Superoxide Dismutase / drug effects
  • Superoxide Dismutase / metabolism
  • Tetrazolium Salts
  • Treatment Outcome


  • Calcium Channel Blockers
  • Neuroprotective Agents
  • Tetrazolium Salts
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III
  • Superoxide Dismutase
  • fasudil