Stimulating Circle of Willis Nerve Fibers Preserves the Diffusion-Perfusion Mismatch in Experimental Stroke

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Abstract
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). Conclusion— 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.