Preventive Effect of Low Intensity Pulsed Ultrasound against Experimental Cerebral Ischemia/Reperfusion Injury via Apoptosis Reduction and Brain-derived Neurotrophic Factor Induction

Stroke is known as the top 10 causes of death worldwide. Development of effectively neuroprotective or preventive strategies for ischemia stroke is imperative. For the purpose of stroke prevention, we tested the neuroprotective effects of low-intensity pulsed ultrasound (LIPUS) on ischemic stroke. Adult C57BL/6 mice were used to daily treatment with LIPUS for 5 days on left hemisphere before middle cerebral artery occlusion (MCAO)-induced cerebral ischemia/reperfusion injury. Western blotting and immunohistochemistry were performed to assess the protein expressions of signaling molecules. Pretreatment with LIPUS significantly ameliorated the brain ischemic damage, including the reduction of neurological deficit score, infarct area, histopathological score, and showed a better performance in neurological and behavior functions. LIPUS pretreatment could also significantly decrease the neuronal cell apoptosis and upregulation of apoptosis-related signaling molecules and downregulation of brain-derived neurotrophic factor (BDNF) in brain tissues of MCAO-treated mice. Furthermore, LIPUS significantly prevented the decreased cell viability, the increased caspase-3 cleavage, and the decreased BDNF expression in ischemia/reperfusion-treated microglial cells. These results demonstrate that LIPUS effectively prevented the cerebral ischemia/reperfusion injury through apoptosis reduction and BDNF induction in a MCAO mouse model. The neuroprotective potential of LIPUS may provide a novel preventive strategy for ischemic stroke in high-risk patients.