Abstract

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.

Highlights

  • Stroke is known as the top 10 causes of death worldwide

  • low-intensity pulsed ultrasound (LIPUS) significantly prevented the decreased cell viability, the increased caspase-3 cleavage, and the decreased brain-derived neurotrophic factor (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 middle cerebral artery occlusion (MCAO) mouse model

  • These results indicated that pre-administration with LIPUS obviously improved MCAO/reperfusion-induced action ability loss and pathological changes in mice

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Summary

Introduction

Stroke is known as the top 10 causes of death worldwide. Development of effectively neuroprotective or preventive strategies for ischemia stroke is imperative. LIPUS treatment could increase the protein levels of neurotrophic factors, which activate integrin receptor signaling to protect brain astrocytes against injury in an aluminum-induced brain disorder rat model[12] and improve damages in the hippocampus and corpus callosum in a rat vascular dementia model[13]. These findings suggested that LIPUS potentially stimulated the release of neurotrophic factors to contract brain damages. We hypothesized that LIPUS pre-treatment possesses the preventive effects on middle cerebral artery occlusion (MCAO)/reperfusion-induced brain injury via BDNF induction. We tested the protective effect of LIPUS on ischemia/reperfusion-induced cell injury in cultured microglial cells

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