Abstract WP407: Function and Reactivity of Pial Collaterals In Vivo in Normotensive and Hypertensive Rats Response to Ischemia and Reperfusion

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Background: Collateral therapeutics is an emerging treatment for acute ischemic stroke. However, whether pial collaterals have tone in vivo and thus the ability to vasodilate is not clear. We investigated the function of pial collaterals in vivo during ischemia and reperfusion in normotensive and hypertensive rats that are known to have poor collaterals. We hypothesized that pial collaterals from spontaneously hypertensive rats (SHR) would have greater basal tone during ischemia and reperfusion than normotensive Wistar rats that could contribute to decreased collateral perfusion.Methods: A cranial window was performed in SHR (n=4) and Wistar (n=4) rats prior to remote middle cerebral artery occlusion (MCAo) under pentobarbital anesthesia. Video microscopy was used to measure changes in diameter of leptomeningeal anastomoses (LMAs) during MCAo for 2 hrs and 2 hrs reperfusion (Figure, top). After reperfusion, the brain surface was exposed to physiological saline solution with EDTA (67 mmol/L) to measure fully relaxed diameters and calculate basal tone. Blood pressure was measured via arterial catheter and animals were mechanically ventilated to control blood gases.Results: Blood pressure was significantly elevated in SHR vs. Wistar rats (157±9 vs. 107±7; p<0.01). LMAs (~15-20 μm diameters) had basal tone that was higher in SHR vs. Wistar (15.4±9% vs. 8.4±4.9%; n.s.). After 5 min MCAo, tone in LMAs from Wistar rats decreased to 2.7±1.5% but increased to 17.2±9.7% in SHR. Reperfusion caused vasoconstriction of LMAs from both groups and increased tone to 18.7±5.3% in Wistar and to 29.5±9.7% in SHR (p<0.01 vs. basal for both; Figure, bottom).Conclusions: These data demonstrate functional pial collaterals in normotensive and hypertensive rats. While increased tone of LMAs during MCAo in SHR could limit perfusion to the penumbra, vasoconstriction of LMAs from both groups suggests therapeutic intervention to increase diameter and salvage at risk tissue is possible.

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