Budget Amount *help |
¥3,890,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
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Research Abstract |
Sprague-Dawley rats were subjected to MCAo using an intraluminal suture technique fir 90 minutes. The rats were reperfused for 24 hours and decapitated for infarct and edema analysis . Animals were randomly divided into the following four groups. (I) vehicle-treated control group 0:) low dose of fasudil (3.0 mg/kg)-treated+ normothennia (37℃) group (III) fasudil (3.0 mg/kg)treated + hypothermia (35℃) group (IV) edaravone-treated group. A rho-kinase inhibitor-treated animals received a continuous injection of fasudil (3.0 mg/kg) intravenously fir 60 minutes after the onset of ischemia, while vehicle-treated groups received same dose of vehicle. During ischemia, temporal muscle and rectal temperatures were monitored and maintained at 37 or 35 degrees in the experimental animals. Neurological symptom evaluations (posture and hemiplegia) were perfumed immediately before infarct and edema analysis. Furthermore, cortical cerebral blood flow was measured during ischemia and reperfusion. Physi
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ological Paramers (PH, P02, PCO2, Blood Sugar, Brain and Body Temperature) has no statistical difference between the groups. The cortical blood flow also has no statistical difference between the groups. Low dose fasudil (3.0 mg/kg) showed infant volume smaller compared to the vehicle-heated animal. Furthermore, extra-mild hypothermia (35℃) with fasudil showed infarct more smaller compared to 37℃ fasudil treated animal. The cortical and striatal infarct volume (85±42 mm3) in the low dose of fasudil-treated group (group III) was significantly less than those in group I (195±36 mm3, p<0.001). Law dose Fasudil + hypothermia (group IV) decreased the cortical or striatal infarct volume ( 76±49 mm3, 35±22 mm3) significantly (p<0.001, P<0.01, respectively) compared with those of groups I (195 ± 36 mm3, 83 ± 20 mm3 ), whereas hypothermia-treated only (group II) did not decreased cortical and striatal infarct volume significantlyLow dose Fasudil (group II) decreased the cortical edema volume (34±18 mm3,) significantly (p<0.05) compared with those of groups I (73 ± 25 mm3), whereas low dose fasudil did not decreased the striatal edema volume (38±14 mm3) significantly Fasudil + hypothermia (group IV) decreased the cortical infarct volume ( 35 ± 22 mm3) significantly (p<0.001) compared with those of groups I Fasudil reduced expression of the proapoptotic Bax protein in the penumbra, whereas it inc eased upregulation of the antiapoptotic protein Bcl-2 in this area Furthermore, TUNEL positive rats were decreased after administration of fasudil in the penumbra. Less
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