A neuroprotective brain stimulation for vulnerable cerebellar Purkinje cell after ischemic stroke: a study with low-intensity focused ultrasound.

Abstract

The role of established contralateral cerebrocerebellar connections on cerebellar injury during stroke has been increasingly revealed in recent years. An extensive number of studies have investigated alteration in inter-hemispheric correlation in order to find brain regions whose responses are specific to restore functional loss and enhance adaptive neural plasticity after stroke. Although, several non-invasive brain stimulation studies have proven their efficacy in the treatment of stroke recovery, finding more effective brain regions that responsible for stroke rehabilitation as well as optimizing neural stimulation protocol are the main goals of further investigations. In this study, the lateral cerebellar nucleus (LCN) was exposed to Low-Intensity Focused Ultrasound (LIFU) to reduce the cerebellar damage resulting from crossed cerebellar diaschisis (CCD) phenomenon after cerebral ischemia. A mouse brain ischemia was induced by middle cerebral artery occlusion (MCAO). A level of decrease in Purkinje cell (PC) number and a quantity of myeloperoxidase (MPO) positive neutrophils in the cerebral cortex were compared between stroke and stroke+LIFU groups after MCAO. In stroke+LIFU group, the increased ipsilateral water content due to tissue swelling was observed, showing an attenuation of brain edema. Prominently, the reduction of the neuroimmune reactivity at the infarct core and the peri-infarct regions, and the increased rate of survival among PCs clearly demonstrated primary evidence of neuroprotective effect induced by LIFU-mediated cerebellar modulation.