BACKGROUND AND PURPOSE: Stimulation of the nerves traversing the ethmoidal foramen (including postsynaptic, parasympathetic projections from the sphenopalatine ganglion [SPG], henceforth referred to as "SPG-stimulation") has been shown to elevate cerebral blood flow (CBF) and to be neuroprotective after permanent, middle cerebral artery occlusion (pMCAO). METHODS: Employing diffusion (DWI)- and perfusion (PWI) weighted MRI, the effect of SPG-stimulation (started at 60 minutes post-MCAO) on the spatiotemporal evolution of ischemia during and after pMCAO was investigated. In an additional experiment, regional CBF changes were investigated in the nonischemic brain. RESULTS: In the nonischemic brain, SPG stimulation significantly elevated CBF predominantly within areas supplied by the anterior cerebral artery (by 0.64 mL/g/min relative to baseline). In the ischemic brain, CBF only marginally increased within the penumbra and core (by up to 0.08 and 0.15 mL/g/min relative to prestimulation, respectively). However, the threshold-derived CBF lesion volume did not change significantly. Penumbral apparent diffusion coefficient (ADC)-values improved to almost baseline values and the threshold derived ADC/CBF-mismatch was preserved up to 180 minutes after MCAO. TTC-derived lesion volumes were significantly smaller in stimulated versus nonstimulated animals (120.4+/-74.1 mm(3) versus 239.3+/-68.5 mm(3), respectively). CONCLUSIONS: This study demonstrates that unilateral SPG-stimulation increases CBF bilaterally within the normal brain, acutely preserves the CBF/ADC mismatch largely independent of altering cerebral blood flow, and reduces infarct size in the rat permanent suture model.