Sirolimus Alleviates Experimental Subarachnoid Hemorrhage Induced Vasospasm

細胞內訊息下傳抑制物Sirolimus防止實驗性蜘蛛膜下腔出血引起的血管痙攣

張志任(Chih-Zen Chang) ； 關暟麗(Aij-Lie Kwan) ； 洪純隆(Shen-Long Howng)

《南臺灣醫學雜誌》 3卷3期 (2007/12) Pp. 126-131

https://doi.org/10.6726/MJST.200712_3(3).0002

摘要

Background: Sirolimus is known to be a potent immunosupressive agent. However it has not been previously investigated in the management of cerebral vasospasm following subarachnoid hemorrhage. Methods: The rodent femoral artery model of vasospasm was employed. 20 male Sprague-Dawley rats (250-350g) were randomly assigned to 2 different groups. Dosages were selected based upon pilot data and drug pharmacokinetic studies. Vasospasm was evaluated at post-hemorrhage day 8 (the point of peak constriction in this model). Vasospasm was evaluated by calculation of cross-sectional vessel area and radial wall thickness using computerized video analysis and was expressed as percent lumen potency (ratio of blood exposed to non-blood exposed vessel). Monoclonal CD45 immunostaining for leukocyte was evaluated (x200). Results: Significant vasospasm was noted in the vehicle treated group (lumen potency 69.3%, p≤0.01). Insignificant vasospasm was noted in the Sirolimus treated groups (Lumen potency, 92.3% for the Sirolimus groups, p=0.41). Additionally, infiltration of inflammatory cells was qualitatively less in the sirolimus treated groups compared to the vehicle treated group. Quantification of CD45 positive leukocyte infiltration is prominent in the control hemorrhage site of the vehicle treatment group (mean 30.3±3.2 vas. 66.6±5A in 200 μm2). Conclusions: Administration of cell downstream signal inhibitor sirolimus, extensively decreased CD45 positive leukocytes, devoid experimental post-hemorrhagic vasospasm and is meritorious of further investigation. This study supports a role for inflammation in the development of vasospasm and anti-inflammatory agent could play a role in the therapeutics in the future study.

關鍵字

sirolimus ； 血管痙攣 ； CD45

並列摘要

Background: Sirolimus is known to be a potent immunosupressive agent. However it has not been previously investigated in the management of cerebral vasospasm following subarachnoid hemorrhage. Methods: The rodent femoral artery model of vasospasm was employed. 20 male Sprague-Dawley rats (250-350g) were randomly assigned to 2 different groups. Dosages were selected based upon pilot data and drug pharmacokinetic studies. Vasospasm was evaluated at post-hemorrhage day 8 (the point of peak constriction in this model). Vasospasm was evaluated by calculation of cross-sectional vessel area and radial wall thickness using computerized video analysis and was expressed as percent lumen potency (ratio of blood exposed to non-blood exposed vessel). Monoclonal CD45 immunostaining for leukocyte was evaluated (x200). Results: Significant vasospasm was noted in the vehicle treated group (lumen potency 69.3%, p≤0.01). Insignificant vasospasm was noted in the Sirolimus treated groups (Lumen potency, 92.3% for the Sirolimus groups, p=0.41). Additionally, infiltration of inflammatory cells was qualitatively less in the sirolimus treated groups compared to the vehicle treated group. Quantification of CD45 positive leukocyte infiltration is prominent in the control hemorrhage site of the vehicle treatment group (mean 30.3±3.2 vas. 66.6±5A in 200 μm2). Conclusions: Administration of cell downstream signal inhibitor sirolimus, extensively decreased CD45 positive leukocytes, devoid experimental post-hemorrhagic vasospasm and is meritorious of further investigation. This study supports a role for inflammation in the development of vasospasm and anti-inflammatory agent could play a role in the therapeutics in the future study.

並列關鍵字

sirolimus ； vasospasm ； Cd45