To this end, available treatments in stroke focus on improving brain tissue perfusion. Targeting vascular injury/BBB dysfunction or immune response within the peri-ischemic region is not yet a treatment option. Thus, intravenous recombinant tissue plasminogen activator and mechanical recanalization remain the only approved treatments for stroke. The fundamental limitation of these therapies is the short treatment window. Moreover, symptomatic hemorrhagic transformation of the infarct associated with the administration of IV r-tPA remains a primary concern. In the USA, for example, only about 4% of ischemic stroke patients are treated with IV r-tPA. Hence, there is substantial interest in developing novel therapeutics for the treatment of acute cerebral ischemia. The aims of the present study were to use imaging methods to test directly the effect of SPG stimulation on vascular diameter and permeability, rCBF, infarct size and neuronal network activity in the acutely ischemic cortex. A better insight into the mechanisms underlying the effects of SPG may improve patient selection and follow-up, and improve the use of SPG stimulation as a new therapeutic modality for brain disorders. In the present study, we examined – for the first time– the effect of SPG stimulation on the diameter and blood flow in surface cortical vessels in healthy and ischemic brains. We further tested the effect of repetitive SPG stimulation on cortical electrophysiology within the peri-infarct region in the photothrombosis model. The main findings of this study were: SPG stimulation led to intensity- and pulse width dependent vasodilation and increased rCBF; SPG-induced vasodilation facilitated partial reperfusion of occluded vessels in the phothrombosis RB model; the periischemic zone showed increased permeability of the BBB, which was reduced in size both immediate and delayed stimulation of the SPG; the necrotic core lesion was smaller following SPG treatment; fast cortical electrical activity and seizure-like events were prominent from day 3 after photothrombosis and reduced to control levels in SPG treated animals. A milder effect on rCBF was reported by Henninger and Fisher in rats, when isoflurane anesthesia was used, perhaps because of the vasodilating effect of isoflurane. While previous studies in monkeys demonstrated that SPG stimulation induces dilatation of constricted large vessels, in a sub-arachnoid hemorrhage model, our study shows that similar dilation occurs in small surface arterioles of the healthy brain. EX 527 Recently, similar protocol has been shown to increase perfusion in MRI scans of rats following MCAO occlusion, suggesting that the vasodilation we observed in superficial vessels reflects a general response of both superficial and deep vessels to stimulation of the parasympathetic fibers of the greater superficial petrosal nerves. Notably, using the direct imaging approach we show for the first time in a stroke model, that SPGinduced vasodilation may result in immediate reperfusion of the ischemic core.