Abstract
Background: Stroke is known as the top 10 causes of death worldwide. There is a medical emergency for stroke, but most acute ischemic stroke patients are too late to receive thrombolytic treatment. Therapeutic ultrasound has been to obtain clinical acceptance. Low-intensity pulsed ultrasound (LIPUS) belongs to an ultrasound with non-thermal mechanism and can output in a pulse wave mode that is delivered at a much lower intensity than traditional ultrasound energy. For the purpose of stroke prevention, we tried to test the neuroprotective effect of brain-derived neurotrophic factor (BDNF) induction by LIPUS on ischemic stroke.
Methods: Adult male C57BL/6 mice were used to daily treatment with LIPUS (intensity 528 mW/cm2) for 5 days (15 min daily) on left hemisphere before middle cerebral artery occlusion (MCAO)-induced cerebral ischemia/reperfusion injury. Western blot analysis and immunohistochemistry were performed to assess the protein expressions of signaling molecules. Moreover, a microglial cell model was used to test the in vitro effects of LIPUS.
Results: Pretreatment with LIPUS effectively and significantly ameliorated the brain ischemic damage, including the reduction of neurological deficit score, infarct area, histopathological score, and showed a better performance in neurological functions in MCAO-treated mice (n=6, P<0.05; Figure 1A-C). LIPUS pretreatment could also significantly decrease the neuronal cell apoptosis and upregulation of apoptosis-related signaling molecules and downregulation of BDNF in brain tissues of MCAO-treated mice (n=6, P<0.05; Figure 1D and E). Furthermore, LIPUS in vitro exposure significantly prevented the decreased cell viability, the increased caspase-3 cleavage, and the decreased BDNF expression in ischemia/reperfusion-treated microglial cells (n=4, P<0.05).
Conclusions: These results demonstrate that LIPUS treatment effectively triggers BDNF induction and prevented the cerebral ischemia/reperfusion injury through apoptosis reduction in a MCAO mouse model. The neuroprotective potential of BDNF induction by LIPUS may provide a novel preventive strategy for ischemic stroke in high-risk patients.
