Time-Dependent Alterations in Functional and Pharmacological Arteriolar Reactivity After Subarachnoid Hemorrhage

Abstract

Background and Purpose-Disturbances in cerebral arteriolar function, in addition to large vessel vasospasm, may be responsible for ischemia after subarachnoid hemorrhage. The purpose of this study was to test the hypothesis that subarachnoid hemorrhage alters cerebral microvascular reactivity. Methods-An endovascular filament model was used to induce subarachnoid hemorrhage in halothane-anesthetized male Sprague-Dawley rats. We evaluated pial arteriolar responses to sciatic nerve stimulation, topically applied vasoactive agents (adenosine or sodium nitroprusside), and CO 2 inhalation in rats subjected to subarachnoid hemorrhage at 1 to 5 days after insult. Results-In sham-operated rats, sciatic nerve stimulation evoked a 23.5Ϯ1.8% increase in arteriolar diameter, which was significantly attenuated to 13.7Ϯ0.9%, 12.8Ϯ2.5%, and 18.8Ϯ2.9% at 24, 48, and 72 hours after subarachnoid hemorrhage, respectively (PϽ0.05; nՆ7). At 96 and 120 hours after subarachnoid hemorrhage, sciatic nerve stimulation-induced dilation recovered to sham levels. Somatosensory-evoked potentials were unaltered by subarachnoid hemorrhage. Pial vasodilatation to adenosine (10 mol/L) and sodium nitroprusside (1 mol/L) were significantly impaired, by 47% and 41%, respectively, at 48 hours after subarachnoid hemorrhage (PϽ0.05; nϭ7). In contrast, CO 2 reactivity was unaffected by subarachnoid hemorrhage. Conclusions-Pial arteriolar responses to cortical activation may be decreased in the initial 2 to 3 days after experimental subarachnoid hemorrhage.

Constriction and dysfunction of pial arterioles after regional hemorrhage in the subarachnoid space

“…In contrast to our findings, Britz et al obtained conflicting results using CO 2 , adenosine, and sodium nitroprusside (SNP) in an endovascular filament model of SAH in rats (Britz et al, 2007). They found that CO 2 reactivity was unaffected by SAH.…”

The Role of HMGB1 in Pial Arteriole Dilating Reactivity following Subarachnoid Hemorrhage in Rats

“…Our results demonstrated that SAH impaired the pial dilating response to common vascular dilating stimuli, such as SNS, CO 2 , ACh, and ADO, which is consistent with previous reports [16,20,21]. However, inhibition of HMGB1 by its antagonist or receptor-binding inhibitors did not change the response, suggesting that HMGB1 might not play a significant role in pial vessel reactivity during SAH, at least in our rat model of SAH.…”

Pharmacologic blockade of vascular adhesion protein-1 lessens neurologic dysfunction in rats subjected to subarachnoid hemorrhage

“…Evidence obtained in rodents (Britz et al, 2007;Jorks et al, 2011;Koide et al, 2012) suggested that vasodilatory impairments following SAH could arise in arterioles, and may be linked to the elevated presence of inflammatory factors (Kolias et al, 2009;Pradilla et al, 2010). Findings from our laboratory, in rats subjected to transient focal ischemia (Watcharotayangul et al, 2012) or transient forebrain ischemia (TFI), (Xu et al, 2006) suggested a direct correlation between post-ischemic pial venular leukocyte activity and brain damage.…”