Neuroprotective effects of fasudil, a Rho-kinase inhibitor,in a rat transient forebrain ischemia-reperfusion model

  • Kodama Sahoko
    Department of Anesthesia and Intensive Care Medicine, Akita University Graduate School of Medicine
  • Kimura Tetsu
    Department of Anesthesia and Intensive Care Medicine, Akita University Graduate School of Medicine
  • Nishikawa Toshiaki
    Department of Anesthesia and Intensive Care Medicine, Akita University Graduate School of Medicine
  • Horiguchi Takashi
    Department of Anesthesia and Intensive Care Medicine, Akita University Graduate School of Medicine

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  • Neuroprotective effects of fasudil, a Rho-kinase inhibitor, in a rat transient forebrain ischemia-reperfusion model

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<p>Background:Because cerebral ischemia activates Rho/Rho-kinase pathway, we investigated whether fasudil, a Rho-kinase inhibitor, improves neurologic and histopathologic outcomes, and whether apoptosis is involved in the neuroprotective property of fasudil in a rat transient forebrain ischemia-reperfusion model. </p><p> Methods:Forty male Sprague-Dawley rats received intraperitoneal injection of physiological saline (C), fasudil 3, 10, or 30 mg/kg (F3, F10, F30) 24 and 48 h before insult. Forebrain ischemia was induced by hemorrhagic hypotension and bilateral carotid artery occlusion for 10 min. Neurologic scores (0 points:worst, 18 points:normal) were evaluated at 24, 48 and 72 h after ischemia, followed by histologic evaluation with haematoxylin/eosin and TUNEL staining. </p><p> Results:The median neurologic score in the group F10 was significantly higher than that in the group C at 72 hours after cerebral ischemia (P < 0.05). The percentages of intact neurons in the hippocampal CA1 region were greater in the groups F3 and F10 than the group C (P < 0.05). Although the numbers of TUNEL positive cells in the hippocampal CA1 region tended to be less in the groups F3 and F10 compared to the group C, there was no statistical difference among the groups. </p><p> Conclusion:Our results demonstrated that pre-treatment with fasudil 10 mg/kg, but not 30 mg/kg, improved both neurologic and histologic outcomes in a rat transient forebrain ischemia-reperfusion model. Apoptosis may not contribute to the neuroprotective effects of fasudil in this model.</p>

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