Changyaleket Benjarat, Chong Zhao Zhong, Dull Randal O, Nanegrungsunk Danop, Xu Haoliang
Department of Anesthesiology, University of Illinois at Chicago, Chicago, IL, USA.
Department of Pathology, University of Illinois at Chicago, 840 South Wood Street, Chicago, IL, 60612, USA.
J Neuroinflammation. 2017 Jul 18;14(1):137. doi: 10.1186/s12974-017-0912-8.
Heparanase, a mammalian endo-β-D-glucoronidase that specifically degrades heparan sulfate, has been implicated in inflammation and ischemic stroke. However, the role of heparanase in neuroinflammatory response in subarachnoid hemorrhage (SAH) has not yet been investigated. This study was designed to examine the association between heparanase expression and neuroinflammation during subarachnoid hemorrhage.
Rats were subjected to SAH by endovascular perforation, and the expression of heparanase was determined by Western blot analysis and immunofluorescence in the ipsilateral brain cortex at 24 h post-SAH. Pial venule leukocyte trafficking was monitored by using intravital microscopy through cranial window.
Our results indicated that, compared to their sham-surgical controls, the rats subjected to SAH showed marked elevation of heparanase expression in the ipsilateral brain cortex. The SAH-induced elevation of heparanase was accompanied by increased leukocyte trafficking in pial venules and significant neurological deficiency. Intracerebroventricular application of a selective heparanase inhibitor, OGT2115, which was initiated at 3 h after SAH, significantly suppressed the leukocyte trafficking and improved the neurological function.
Our findings indicate that heparanase plays an important role in mediating the neuroinflammatory response after SAH and contributes to SAH-related neurological deficits and early brain injury following SAH.
乙酰肝素酶是一种特异性降解硫酸乙酰肝素的哺乳动物内切-β-D-葡糖醛酸酶，与炎症和缺血性中风有关。然而，乙酰肝素酶在蛛网膜下腔出血（SAH）的神经炎症反应中的作用尚未得到研究。本研究旨在探讨蛛网膜下腔出血期间乙酰肝素酶表达与神经炎症之间的关联。
通过血管内穿刺使大鼠发生蛛网膜下腔出血，并在蛛网膜下腔出血后24小时通过蛋白质免疫印迹分析和免疫荧光法测定同侧大脑皮质中乙酰肝素酶的表达。通过颅窗利用活体显微镜监测软脑膜微静脉白细胞运输情况。
我们的结果表明，与假手术对照组相比，蛛网膜下腔出血大鼠同侧大脑皮质中乙酰肝素酶的表达显著升高。蛛网膜下腔出血诱导的乙酰肝素酶升高伴随着软脑膜微静脉中白细胞运输增加和明显的神经功能缺损。在蛛网膜下腔出血后3小时开始脑室内应用选择性乙酰肝素酶抑制剂OGT2115，可显著抑制白细胞运输并改善神经功能。
我们的研究结果表明，乙酰肝素酶在介导蛛网膜下腔出血后的神经炎症反应中起重要作用，并导致蛛网膜下腔出血相关的神经功能缺损和蛛网膜下腔出血后的早期脑损伤。
