Therapeutic modulation of intracranial collateral flow improves outcome in experimental ischemic stroke

Objective: intracranial collateral circulation performance is emerging as a strong outcome determinant in both human and experimental ischemic stroke. The aim of this study was to investigate and compare the effects of two putative strategies, which might actively modulate intracranial collateral flow in the setting of acute cerebral ischemia: intravascular volume load using polygeline and cerebro-selective vasodilatation using acetazolamide. Materials and methods: MCA was transiently occluded (90 min) by intraluminal filament in adult male Wistar rats. 10 rats were left untreated; 30 rats were treated after 30 min of ischemia with intravenous administration of either saline solution (n=10), polygeline (n=10) or acetazolamide (n =10). Intracranial collateral flow was studied in terms of perfusion deficit using multi-site laser Doppler monitoring, functional deficit was assessed using a sensory-motor score and infarct volume was calculated on consecutive sections stained with Cresyl violet, performed 24 hours after ischemia induction. Blood pressure, heart and respiratory rate were continuously monitored by a pressure transducer placed in femoral artery. Results: post-ischemic administration of both polygeline and acetazolamide significantly increased intracranial collateral flow in the territory of leptomeningeal branches during MCA occlusion and reduced infarct size as well as functional deficit, compared to untreated and saline-treated rats. No significant effect on blood pressure was observed. Conclusions: therapeutic modulation of intracranial collateral flow is feasible and is associated with a better outcome after transient MCA occlusion in rats. “Collateral therapeutics” may represent an simple tissue-saving strategy in the hyper-acute phase of ischemic stroke prior to recanalization therapy.