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).
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 results from
group I animals in which the IS/risk area (RA) ratio was measured 24 h later. Group
III included 38 normal mice undergoing US treatment/no treatment for assessment of
CBF, tissue metabolite and protein expression and histopathology.
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.
Keywords
Abbreviations:
US (ultrasound), MCAO (middle cerebral artery occlusion), OGD (oxygen glucose deprivation), p-eNOS (phosphorylated endothelial nitric oxide), EETs (epoxyeicosatrienoates), HETEs (hydroxyeicosatetraenoates), CBF (cerebral blood flow), PRAPAS (peak rarefactional acoustic pulse amplitudes), RA (risk area), IS (infarct size), TTC (tripheyl tetrazolium chroride), CH (cerebral hemisphere), CP (caudate putamen), CC (cerebral cortex), Ispta (Acoustic intensity, spatial peak temporal average), Isppa (Acoustic intensity, spatial peak pulse average), ELISA (enzyme-linked immunosorbent assay)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: February 02, 2023
Accepted:
December 16,
2022
Received in revised form:
December 13,
2022
Received:
September 27,
2022
Identification
Copyright
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