Extravascular Blood Augments Myogenic Constriction of Cerebral Arterioles: Implications for Hemorrhage‐Induced Vasospasm

Abstract

BackgroundSubarachnoid hemorrhage is a serious clinical condition that impairs local cerebral blood flow perfusion and consequently initiates neuronal dysfunction. Pressure‐sensitive myogenic vasomotor regulation is an important mechanism involved in the regulation of cerebral blood flow. We hypothesized that extravascular hemolyzed blood enhances arteriolar myogenic constriction, which in vivo may contribute to the reduction of local cerebral blood flow after subarachnoid hemorrhage.Methods and ResultsArterioles isolated from the middle cerebral artery (MCA arterioles) of mice were cannulated in a perfusion chamber. Arteriolar diameters in response to step increases in intraluminal pressure (20–120 mm Hg) were measured in various experimental conditions. In response to increases in intraluminal pressure, all MCA arterioles exhibited myogenic vasoconstrictions. Compared with controls, the pressure‐induced constriction was significantly enhanced in arterioles (in vitro) exposed to extravascular hemolyzed blood or different concentrations of extracellular erythrocyte lysate (1%, 10%, and 20%) for different exposure durations (1–6 hours). The magnitude of enhancement was proportional to the lysate concentration and exposure duration. In in vivo experiments, 10 μL of autologous blood lysate were injected into the mouse subarachnoid space on the surface of the left MCA. Two hours later, MCA arterioles were isolated and left MCA arterioles displayed enhanced myogenic responses compared with the right MCA. The enhanced myogenic response was prevented by scavenge of superoxide in both in vitro and in vivo experiments.ConclusionsExtravascular hemolyzed blood, perhaps by promoting vascular production of superoxide, augments myogenic constriction of cerebral arterioles, which plays a crucial role in the subarachnoid hemorrhage–induced cerebral ischemia.

Cerebral Autoregulation in Subarachnoid Hemorrhage

“…Only a handful of studies have utilized cannulated resistance arteries ex vivo to investigate the effects of SAH on myogenic reactivity (Table 1). As demonstrated in mouse olfactory (87,93) and middle cerebral (94), rat parenchymal (95,96) and middle cerebral (97), canine basilar (98), and rabbit cerebellar and posterior cerebral resistance arteries (99,100), these studies are unanimous in concluding that SAH augments cerebral resistance artery myogenic reactivity. Through the use of endothelial denudation (95), smooth muscle cell specific gene deletion (87) and studies on freshly isolated artery myocytes (96,100), this pathological effect can be attributed to a change in smooth muscle cell function.…”

Systemic exosomal miR-193b-3p delivery attenuates neuroinflammation in early brain injury after subarachnoid hemorrhage in mice

“…As described in a previous study [24], mice were intraperitoneally anesthetized with 4% chloral hydrate (0.4 g/ kg body weight). They were then placed in the stereotaxic apparatus.…”

Antioxidant Melatonin: Potential Functions in Improving Cerebral Autoregulation After Subarachnoid Hemorrhage

“…Thus, high concentration of ROS (derived from blood) may augment the myogenic tone via directly and indirectly mediate vascular smooth muscle after SAH. Recently, a study from Deng et al (2018) provided direct evidence. They studied the effects of extravascular hemolyzed blood on arteriolar myogenic constriction and found that extravascular hemolyzed blood augments the myogenic constriction of cerebral arterioles, possibly by increasing the vascular production of superoxide.…”