Partial Aortic Occlusion For Middle Cerebral Occlusion Model In Rabbits: Analysis Of Therapeutic Time Window

Objective: Collateral circulation provides an alternative route for blood flow to reach ischemic tissue during a stroke.Blood flow through cerebral collateral is critical predictor of clinical prognosis after stroke and response to recanalization.Collateral therapeutics are attempted to augment flow through these collateral channels to reduce ischemia and brain damage during acute ischemic stroke.Partial aortic occlusion(PAO)has pre-clinical and clinical data suggesting for ischemic stroke by diverting blood from the periphery towards the cerebral circulation.However,the optimal therapeutic time window has not been completely understood.In this study,we investigated the relationship between the timing of PAO and its efficacy in ischemic stroke model in rabbits.Methods: 50 New Zealand white rabbits received right middle cerebral artery occlusion(MCAO).PAO was conducted at either 3,6,12,24 hours(3,6,12,24 h group)after MCAO.Rabbits in control group did not received PAO.Cerebral blood flow(CBF)was measured at 1hour after MCAO and immediately after PAO using CT perfusion imaging(CTPI).Behavioral test was performed at 1hour,3 days,7 days after MCAO using the Neurological Severity Score(NSS).Rabbits were euthanized at 7 days after MCAO for evaluation of infarct volume and apoptosis.Results: 1 Excluding the failure models,the rabbits were divided into 3h group(n=7),6h group(n=9),12 h group(n=8),24 h group(n=7),control group(n=8);2 There was significantly improvement of CBF in 3h,6h,12 h group compared to control group after PAO(P<0.05).Although the CBF in 24 h group was increased compared to that in the control group(P<0.05),it was significantly decreased compared to that in the 3h,6h,12 h group(P<0.05);3 Behavioral test at 3 and 7 days after PAO revealed that stroke rabbits in 3h,6h,12 h group displayed the most robust significant improvements in NSS compared to stroke rabbits in 24 h group and control group(P<0.05).However,there was no significant difference between 24 h group and control group in NSS(P>0.05);4 The infarct volumes of stroke rabbits in 3h,6h,12 h group were much significantly decreased compared to those in 24 h group and control group(P<0.05).There was no significant difference between 24 h group and control group in infarct volumes of stroke rabbits(P>0.05);5 The difference of IHS in different groups is significant at 7days after MCAO(P<0.05).The IHS of 3h group is significantly different from that of 24 h group and control group(P<0.05).Conclusion: These results suggest that PAO provides functional recovery and reduction of infarct volumes of ischemic stroke model of rabbits by improving the CBF deficits.PAO in 12 hours appears to be the optimal time window for ischemic stoke model,which should guide the design of clinical trials of PAO for stoke patients.