Abstract

The incidence of stroke recurrence is still higher despite the advanced progression of therapeutic treatment and medical technology. Low intensity pulsed ultrasound (LIPUS) has been demonstrated to possess therapeutic effects on neuronal diseases and stroke via brain-derived neurotrophic factor (BDNF) induction. In this study, we hypothesized that LIPUS treatment possessed therapeutic benefits for the improvement of stroke recurrence. Adult male C57BL/6J mice were subjected to a middle cerebral artery occlusion (MCAO) surgery and then followed to secondary MCAO surgery as a stroke recurrence occurred after nine days from the first MCAO. LIPUS was administered continuously for nine days before secondary MCAO. LIPUS treatment not only decreased the mortality but also significantly moderated neuronal function injury including neurological score, motor activity, and brain pathological score in the recurrent stroke mice. Furthermore, the administration of LIPUS attenuated the apoptotic neuronal cells and increased Bax/Bcl-2 protein expression ratio and accelerated the expression of BDNF in the brain of the recurrent stroke mice. Taken together, these results demonstrate for the first time that LIPUS treatment arouses the expression of BDNF and possesses a therapeutic benefit for the improvement of stroke recurrence in a mouse model. The neuroprotective potential of LIPUS may provide a useful strategy for the prevention of a recurrent stroke.

Highlights

  • Stroke is the second leading cause of death and the third for disability

  • In order to observe whether Low intensity pulsed ultrasound (LIPUS) treatment ameliorated the neurological status of mice in a recurrent stroke condition, we first assessed the mortality and the changes in neuronal functions, which were performed by rotarod and locomotor activity tests

  • This study has demonstrated for the first time that consecutive administration of LIPUS displays a benefit for recurrent stroke via brain-derived neurotrophic factor (BDNF) induction

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Summary

Introduction

Stroke is the second leading cause of death and the third for disability. Globally, more than 30 million people had suffered the impacts of a stroke and associated disorders as reported in 2016 [1,2]. The recurrent events lead to a prolonged hospitalization, an elevated risk of morbidity and mortality, and the increased medical expenditure or burden [4]. Multi-factorial networks such as respiratory and cardiovascular disease [5,6], diabetes-associated disorders [7] as well as hyperlipidemia [8] potentially increase the risk of ischemic stroke and recurrence. Yamamoto and Bogousslavsky suggested that the coexistence of multiple etiologies plays a major role in stroke recurrence [9]. These complications of mechanisms appear to develop a potential therapeutic treatment or strategy for recurrent ischemic stroke

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