Systemic complement depletion inhibits experimental cerebral vasospasm

Systemic complement depletion inhibits experimental cerebral vasospasm
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DOI:
10.1097/00006123-199607000-00028
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发表时间:
1996-07-01
期刊:
影响因子:
4.8
通讯作者:
Bednar, MM
Bednar, MM
中科院分区:
医学1区
文献类型:
--
作者:
German, JW;Gross, CE;Bednar, MM

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目的:脑血管痉挛是因蛛网膜下腔出血(SAH)住院患者发病和死亡的主要原因。最近的研究表明,补体级联反应的激活有助于脑血管痉挛的发展。为了进一步验证这一假设,采用兔SAH.METHODS模型:自体动脉血2毫升注入中脑周围池区域。诱导SAH后48小时,进行活体灌注固定。基底动脉的形态测定分析用于评估用补体耗竭剂、眼镜蛇毒因子(CVF)或载体预处理后脑血管痉挛的程度。将家兔随机分为四组:1)假手术组(n = 5); 2)假手术+ CVF组(n = 4); 3)SAH组(n = 10);或4)SAH + CVF组(n = 7)。在诱导SAH前24小时,动物接受100单位/kg CVF或溶剂。血清的总溶血潜力证实了显著的CVF治疗后24 h血清补体活性降低(P < 0.05)。CVF预处理显著(P < 0.0083)减少血管痉挛的程度,通过管腔直径从393.9 μ m到100.1 μ m进行评估(平均值+/-标准差)至SAH + CVF组的510.7 +/- 72.8 μ m,与假手术组(594.5 +/- 27.9 μ m)和假手术+ CVF组(587.7 +/- 47.3 μ m)相比。
OBJECTIVE: Cerebral vasospasm is the leading cause of morbidity and mortality in patients who are hospitalized because of aneurysmal subarachnoid hemorrhage (SAH). Recent work has suggested that activation of the complement cascade contributes to the development of cerebral vasospasm. To further examine this hypothesis, a rabbit model of SAH was employed.METHODS: Two milliliters of autologous arterial blood was injected into the region of the perimesencephalic cistern. Forty-eight hours after SAH was induced, intravital perfusion-fixation was performed. Morphometric analysis of the basilar artery was used to assess the extent of cerebral vasospasm after pretreatment with the complement depleting agent, cobra venom factor (CVF), or vehicle. Rabbits were randomized to one of four groups: 1) sham (n = 5); 2) sham + CVF (n = 4); 3) SAH (n = 10); or 4) SAH + CVF (n = 7). Twenty-four hours before induction of SAH, the animals received either 100 units/kg CVF or vehicle. The total hemolytic potential of the serum confirmed a significant (P < 0.05) reduction in serum complement activity 24 hours after the administration of CVF.RESULTS: Pretreatment with CVF significantly (P < 0.0083) reduced the extent of vasospasm, as assessed by lumen diameter from 393.9 a 100.1 mu m (mean +/- standard deviation) in the SAH group to 510.7 +/- 72.8 mu m in the SAH + CVF group, when compared with the sham (594.5 +/- 27.9 mu m) and sham + CVF (587.7 +/- 47.3 mu m) groups.CONCLUSION: The results suggest a role for complement activation in SAH.