Department of Neuroscience, Mount Sinai School of Medicine, New York, NY 10029, USA.
J Neuroinflammation. 2011 Aug 19;8:103. doi: 10.1186/1742-2094-8-103.
Subarachnoid haemorrhage (SAH) elicits rapid pathological changes in the structure and function of parenchymal vessels (≤ 100 μm). The role of neutrophils in these changes has not been determined. This study investigates the role of neutrophils in early microvascular changes after SAH METHOD: Rats were either untreated, treated with vinblastine or anti-polymorphonuclear (PMN) serum, which depletes neutrophils, or treated with pyrrolidine dithiocarbamate (PDTC), which limits neutrophil activity. SAH was induced by endovascular perforation. Neutrophil infiltration and the integrity of vascular endothelium and basement membrane were assessed immunohistochemically. Vascular collagenase activity was assessed by in situ zymography.
Vinblastine and anti-PMN serum reduced post-SAH accumulation of neutrophils in cerebral vessels and in brain parenchyma. PDTC increased the neutrophil accumulation in cerebral vessels and decreased accumulation in brain parenchyma. In addition, each of the three agents decreased vascular collagenase activity and post-SAH loss of vascular endothelial and basement membrane immunostaining.
Our results implicate neutrophils in early microvascular injury after SAH and indicate that treatments which reduce neutrophil activity can be beneficial in limiting microvascular injury and increasing survival after SAH.
蛛网膜下腔出血 (SAH) 会导致实质血管（≤100μm）的结构和功能迅速发生病理变化。中性粒细胞在这些变化中的作用尚未确定。本研究探讨了中性粒细胞在 SAH 后早期微血管变化中的作用。
大鼠未经处理、用长春新碱或抗多形核（PMN）血清处理（耗尽中性粒细胞）或用吡咯烷二硫代氨基甲酸盐（PDTC）处理（限制中性粒细胞活性）。通过血管内穿孔诱导 SAH。免疫组织化学评估中性粒细胞浸润以及血管内皮和基底膜的完整性。通过原位酶谱法评估血管胶原酶活性。
长春新碱和抗 PMN 血清减少了 SAH 后脑血管和脑实质中中性粒细胞的积累。PDTC 增加了脑血管中中性粒细胞的积累，减少了脑实质中的积累。此外，这三种药物都降低了血管胶原酶活性和 SAH 后血管内皮和基底膜免疫染色的丧失。
我们的结果表明中性粒细胞参与了 SAH 后的早期微血管损伤，并表明减少中性粒细胞活性的治疗方法可以通过限制微血管损伤和增加 SAH 后的存活率而受益。
