Heparanase promotes neuroinflammatory response during subarachnoid hemorrhage in rats

Benjarat Changyaleket, Zhao Zhong Chong, Randal O. Dull, Danop Nanegrungsunk, Haoliang Xu

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number137
JournalJournal of Neuroinflammation
Volume14
Issue number1
DOIs
StatePublished - Jul 18 2017
Externally publishedYes

Keywords

  • Heparanase
  • Inflammation
  • Neurological function
  • Subarachnoid hemorrhage

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology
  • Neurology
  • Cellular and Molecular Neuroscience

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