Subarachnoid hemorrhage (SAH) following cerebral aneurysm rupture is associated with high rates of morbidity and mortality. Surviving SAH patients often suffer from neurological impairment, yet little is currently known regarding the influence of subarachnoid blood on brain parenchyma. The objective of the present study was to examine the impact of subarachnoid blood on glial cells using a rabbit SAH model. The astrocyte-specific proteins, glial fibrillary acidic protein (GFAP) and S100B, were up-regulated in brainstem from SAH model rabbits, consistent with the development of reactive astrogliosis. In addition to reactive astrogliosis, cytosolic expression of the pro-inflammatory cytokine, high-mobility group box 1 protein (HMGB1) was increased in brain from SAH animals. We found that greater than 90% of cells expressing cytosolic HMGB1 immunostained positively for Iba1, a specific marker for microglia and macrophages. Further, the number of Iba1-positive cells was similar in brain from control and SAH animals, suggesting the majority of these cells were likely resident microglial cells rather than infiltrating macrophages. These observations demonstrate SAH impacts brain parenchyma by activating astrocytes and microglia, triggering up-regulation of the pro-inflammatory cytokine HMGB1.
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The authors would like to thank Bryce Bludevich, Kevin P. O’Connor, Matthew A. Nystoriak, Edward Zelazny, Todd Clason, Richard A. Hughes, and Keith K. Locke for their helpful comments and assistance with this study. This work was supported by the Totman Medical Research Trust Fund, the Peter Martin Brain Aneurysm Endowment, and NIH NHLBI (R01 HL078983 and P01 HL095488). Research on this project was conducted with the aid of the COBRE Imaging and Cell/Molecular core facilities, which are supported by Grant Number P20 RR016435 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH).
The authors declare no conflicts of interest.
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