High-mobility group box 1 protein (HMGB1) has been implicated in inflammatory responses, and is also associated with cerebral vasospasm after subarachnoid hemorrhage (SAH). However, there are no direct evident links between HMGB1 and cerebral vasospasm. We therefore investigated the effects of HMGB1 on pial arteriole reactivity following SAH in rats. We initially found that SAH induced a significant decrease in pial arteriole dilating responses to sciatic nerve stimulation (SNS), hypercapnia (CO2), and the topical suffusion of acetylcholine (ACh), adenosine (ADO), and s-nitroso-N-acetylpenicillamine (SNAP) over a 7-day period after SAH. The percent change of arteriolar diameter was decreased to the lowest point at 48 h after SAH, in response to dilating stimuli (i.e., it decreased from 41.0 ± 19.0% in the sham group to 11.00 ± 0.70% after SNS) (n = 5, p < 0.01). HMGB1 infusion in the lateral ventricle in normal rats for 48 h did not change the pial arteriole dilating response. In addition, inhibitors of HMGB1-receptor for advanced glycation end-product or HMGB1-toll-like receptor 2/4 interaction, or the HMBG1 antagonist did not improve pial arteriole reactivity 48 h after SAH. These findings suggest that HMGB1 may not be a major player in cerebral vascular dilating dysfunction after SAH.

Keywords:
Receptor for advanced glycation end-product, Toll-like receptor 2/4, Subarachnoid hemorrhage, HMGB1, Pial arteriole, Vasospasm
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2016
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