Implications for understanding ischemic stroke as a sexually dimorphic disease: The role of pial collateral circulations

Abstract

We investigated structural and functional differences in primary and pial collateral circulations in adult normotensive male and female Wistar rats. Male (n = 10) and female (n = 7) rats were subjected to middle cerebral artery (MCA) occlusion and changes in relative cerebral blood flow in MCA and pial collateral territories were measured by multisite laser-Doppler flowmetry. Rats were then transcardially perfused with a mixture of carbon black and latex, perfusion fixed, and imaged to compare primary and pial collateral structure between male (n = 4) and female (n = 3) rats, including lumen diameters and number. To study pial collateral function, leptomeningeal anastomoses (LMAs) were isolated and pressurized from male (n = 7) and female (n = 6) rats. Myogenic tone and reactivity to pressure, vascular function to pharmacological activator, or inhibitor of ion channels was measured and compared. There was no difference between relative cerebral blood flow in both MCA and pial collateral territories during occlusion and reperfusion between groups. Compared with male LMAs, female LMAs had similar myogenic tone (24.0 < 7.3% vs. 16.0 < 3.7%, P > 0.05) and reactivity to increased pressure and similar vascular responses to vaso-constrictive and vasodilatory stimuli. Additionally, compared with female LMAs, male LMAs had similar numbers (21 < 1 vs. 20 < 2, P > 0.05) and diameters (30.5 < 2.0 vs. 26.2 < 0.6 μm, P > 0.05), and no sex difference was detected in the diameter of arterial segments of circle of Willis. Together, our data establish no sex difference of cerebral collateral structure or function, suggesting that the reduced severity of stroke outcome in female rats is not likely due to differences in the cerebral collateral circulation.