Abstract WP151: Rapamycin Improves Post-Recanalization Blood Flow After Acute Experimental Stroke in Rats

Background and Purpose: In the era of thrombectomy, there is evidence suggesting that successful recanalization is not always accompanied by complete reperfusion, the so called “no-reflow phenomenon”. Given the importance of reperfusion as a predictor of stroke outcome, this represents a potential target for stroke therapy. Rapamycin, a clinically approved inhibitor of Mammalian Target of Rapamycin (mTOR) has been shown to improve cerebral blood flow (CBF) in Alzheimer’s disease. However, there has been little investigation into the effect of rapamycin on post-stroke microvascular perfusion. The aim of this study was to investigate the effects of rapamycin treatment on post-recanalisation CBF and stroke outcome in an experimental animal model of stroke. Methods: Male Wistar rats (300-350g) were subjected to 90min of transient middle cerebral artery occlusion (tMCAo) followed by randomized administration of 250μg/kg intravenous rapamycin (n=8) or vehicle (n=6), 30min after the onset of MCAo. Laser Doppler flowmetry was used to continuously measure changes in MCA perfusion during MCAo and for min after recanalisation. Neurobehavioral tests were performed 24hrs after MCAo before tissue was collected for infarct volume measurement. Results: MCAo was confirmed by a 70% reduction in MCA perfusion. Rapamycin treatment significantly improved post-recanalization CBF at 55min after recanalization (p<0.01). Rapamycin significantly increased average CBF during the 60min post-recanalization period (p<0.01). Rapamycin showed a trend towards reduced final infarct volume. Rapamycin significantly improved neuroscores (p<0.05). Post-recanalization CBF was significantly inversely correlated with infarct volume (R 2 =0.4994, p<0.05). Conclusion: Rapamycin significantly improved post-recanalization CBF and behavioural outcomes after MCAo. These results suggest that rapamycin may be an effective acute intervention to improve post-recanalisation blood flow to improve stroke outcome. However, further studies are need to determine the mechanism of improved CBF and if improvements in post-stroke CBF and neurological outcome are sustained long-term post-stroke.