Low-Intensity Ultrasound Reduces Brain Infarct Size by Upregulating Phosphorylated Endothelial Nitric Oxide in Mouse Model of Middle Cerebral Artery Occlusion

低强度超声通过上调小鼠大脑中动脉闭塞模型中的磷酸化内皮型一氧化氮来减少脑梗塞面积

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作者:Catherine M Davis, Azzdine Y Ammi, Wenbin Zhu, Carmen Methner, Zhiping Cao, David Giraud, Nabil J Alkayed, Randy L Woltjer, Sanjiv Kaul

Conclusion

Low-intensity US at specific frequencies and acoustic pressures results in marked neuroprotection in a mouse model of stroke by modulation of p-eNOS independent of its effect on CBF.

Discussion

Ultrasound at both frequencies and most acoustic pressures resulted in reduction in IS in group I animals, with the best results obtained with 0.25 MHz at 2.0 MPa: IS was reduced 4-fold in the cerebral cortex, 1.5-fold in the caudate putamen and 3.5-fold in the cerebral hemisphere compared with control. US application in group III animals elicited only a marginal increase in CBF despite a 2.6-fold increase in phosphorylated endothelial nitric oxide synthase (p-eNOS)-S1177 and a corresponding decrease in p-eNOS-T494. Histopathology revealed no evidence of hemorrhage, inflammation or necrosis. Conclusion: Low-intensity US at specific frequencies and acoustic pressures results in marked neuroprotection in a mouse model of stroke by modulation of p-eNOS independent of its effect on CBF.

Methods

Three groups of mice were studied. Group I included 84 mice with MCAO undergoing US treatment/no treatment at two US frequencies (0.25 and 1.05 MHz) with three different acoustic pressures at each frequency in which infarct size (IS) was measured 24 h later. Group II included 11 mice undergoing treatment based on best US

Objective

There have been attempts to use therapeutic ultrasound (US) for the treatment of both experimental and clinical stroke. We hypothesized that low-intensity US has direct beneficial effects on the brain independent of cerebral blood flow (CBF) during middle cerebral artery occlusion (MCAO).

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