Neuroinflammation Research Center, Lerner Research Institute, NB3, Cleveland Clinic, 9500 Euclid Ave. Cleveland, OH 44195, United States.
J Neuroimmunol. 2011 Mar;232(1-2):94-100. doi: 10.1016/j.jneuroim.2010.10.016. Epub 2010 Nov 6.
The etiology of delayed cerebral vasospasm (DCV) after aneurysmal subarachnoid hemorrhage (SAH) has remained elusive. Growing evidence supports a role for inflammation in the pathogenesis of DCV. We showed that CSF neutrophils predict which patients will develop DCV.
We evaluated a murine model of SAH to test the hypothesis that myeloid cells are required for the cerebral damage associated with DCV.
SAH was associated with decreased middle cerebral artery caliber on day 1 which normalized at day 3 and recurred at day 6. In addition, behavioral testing with a Barnes maze showed executive dysfunction that progressively worsened after the seventh day post hemorrhage. To test the role of innate immune responses, we administrated a myeloid cell-depleting monoclonal antibody against Ly6G/C prior to experimental SAH. Myeloid cell depletion ameliorated angiographic vasospasm measured by MCA vessel caliber and normalized behavioral testing.
Our findings support the role of Ly6G/C(+) cells in the development of DCV after SAH and suggest that immune modulation of neutrophils or other Ly6G/C(+) cells may be a strategy for the prevention of DCV.
动脉瘤性蛛网膜下腔出血（SAH）后迟发性脑血管痉挛（DCV）的病因仍不清楚。越来越多的证据支持炎症在 DCV 发病机制中的作用。我们发现脑脊液中的中性粒细胞可预测哪些患者会发生 DCV。
我们评估了一种 SAH 的小鼠模型，以检验髓样细胞是否是与 DCV 相关的脑损伤所必需的假设。
SAH 后第 1 天，大脑中动脉口径减小，第 3 天恢复正常，第 6 天再次出现。此外，巴恩斯迷宫的行为测试显示，出血后第 7 天，执行功能逐渐恶化。为了测试先天免疫反应的作用，我们在实验性 SAH 前给予针对 Ly6G/C 的髓样细胞耗竭单克隆抗体。髓样细胞耗竭可改善由 MCA 血管口径测量的血管痉挛，并使行为测试正常化。
我们的研究结果支持 Ly6G/C(+)细胞在 SAH 后 DCV 发展中的作用，并表明对中性粒细胞或其他 Ly6G/C(+)细胞的免疫调节可能是预防 DCV 的一种策略。
