Sugawara Takashi, Jadhav Vikram, Ayer Robert, Chen Wanqiu, Suzuki Hidenori, Zhang John H
Department of Physiology, Loma Linda University, Loma Linda, Calif 92354, USA.
Stroke. 2009 Apr;40(4):1530-2. doi: 10.1161/STROKEAHA.108.531699. Epub 2009 Feb 19.
We investigated the role of thrombin in early brain injury after subarachnoid hemorrhage (SAH).
The standard intravascular perforation model was used to produce experimental SAH in Sprague Dawley rats. Low-dose (0.3 mg/h) and high-dose (0.9 mg/h) argatroban, a direct thrombin inhibitor, were evaluated for effects on brain edema, blood-brain barrier (BBB) disruption, apoptotic cell death, inflammatory marker, and neurological outcomes after SAH.
Both doses of argatroban attenuated BBB disruption; however, only high-dose was effective in lowering edema in all brain regions, reducing cell death, and inflammatory marker expression, and improving neurological outcomes.
Thrombin inhibition by argatroban improves neurological outcomes and provides neuroprotection against acute events after SAH such as BBB disruption, brain edema, and cell death.
我们研究了凝血酶在蛛网膜下腔出血(SAH)后早期脑损伤中的作用。
采用标准的血管内穿刺模型在Sprague Dawley大鼠中制造实验性SAH。评估了直接凝血酶抑制剂阿加曲班的低剂量(0.3毫克/小时)和高剂量(0.9毫克/小时)对SAH后脑水肿、血脑屏障(BBB)破坏、凋亡性细胞死亡、炎症标志物及神经功能结局的影响。
两种剂量的阿加曲班均减轻了BBB破坏;然而,只有高剂量在降低所有脑区水肿、减少细胞死亡和炎症标志物表达以及改善神经功能结局方面有效。
阿加曲班抑制凝血酶可改善神经功能结局,并为SAH后的急性事件如BBB破坏、脑水肿和细胞死亡提供神经保护。