Heparanase promotes neuroinflammatory response during subarachnoid hemorrhage in rats

Background: 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. Methods: 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. Results: 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. Conclusions: 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.