TY - JOUR
T1 - Heparanase promotes neuroinflammatory response during subarachnoid hemorrhage in rats
AU - Changyaleket, Benjarat
AU - Chong, Zhao Zhong
AU - Dull, Randal O.
AU - Nanegrungsunk, Danop
AU - Xu, Haoliang
N1 - Publisher Copyright:
© 2017 The Author(s).
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2017/7/18
Y1 - 2017/7/18
N2 - 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.
AB - 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.
KW - Heparanase
KW - Inflammation
KW - Neurological function
KW - Subarachnoid hemorrhage
UR - http://www.scopus.com/inward/record.url?scp=85024391994&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85024391994&partnerID=8YFLogxK
U2 - 10.1186/s12974-017-0912-8
DO - 10.1186/s12974-017-0912-8
M3 - Article
C2 - 28720149
AN - SCOPUS:85024391994
VL - 14
JO - Journal of Neuroinflammation
JF - Journal of Neuroinflammation
SN - 1742-2094
IS - 1
M1 - 137
ER -