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dc.contributor.authorAltay, Orhan
dc.contributor.authorSuzuki, Hidenori
dc.contributor.authorHasegawa, Yu
dc.contributor.authorAltay, Bilge Nur
dc.contributor.authorTang, Jiping
dc.contributor.authorZhang, John H.
dc.description.abstractBackground: Sphingosine kinase (SphK) 1 has been reported as an important signaling node in anti-apoptotic signaling. Heparin is a pleiotropic drug that antagonizes many pathophysiological mechanisms. In this study, we evaluated if heparin prevents early brain injury (EBI) after subarachnoid hemorrhage (SAH) by anti-apoptotic mechanisms including SphK1. Methods: SAH was induced by endovascular perforation in mice, which were randomly assigned to sham-operated (n = 23), SAH + vehicle (n = 36), SAH + 10U heparin pretreatment (n = 13), SAH + 30U heparin pretreatment (n = 15), SAH + 10U heparin posttreatment (n = 31), and SAH + 30U heparin posttreatment (n = 23). At 24 hours post-SAH, neurological scores, brain water content and Evans blue extravasation were evaluated. Also, the expression of SphK, phosphorylated Akt, and cleaved caspase-3 was determined by Western blotting, and cell death was examined by terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling staining. Results: Low-dose heparin posttreatment improved neurobehavioral function, brain edema, blood-brain barrier disruption and cell death in the cortex, associated with an increase in SphK1 and phosphorylated Akt, and a decrease in cleaved caspase-3. High-dose heparin had a tendency for increased SAH severity, which obscured the neuroprotective effects by heparin. Conclusions: Low-dose heparin posttreatment may decrease the development of post-SAH EBI through anti-apoptotic mechanisms including sphingosine-related pathway activation.
dc.titleEffects of low-dose unfractionated heparin on early brain injury after subarachnoid hemorrhage in mice

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