Low-intensity (400Â mW/cm2, 500Â kHz) pulsed transcranial ultrasound preconditioning may mitigate focal cerebral ischemia in rats

•The risk of stroke could be reduced by low-intensity pulsed transcranial ultrasound stimulation preconditioning (pTUS-PC).•pTUS-PC could delay and alleviate hemodynamic compromise during photothrombosis.•pTUS-PC could improve cerebral blood flow (CBF) restoration 24 and 48 h after photothrombosis.•pTUS-PC could reduce infarct volumes and brain edema after ischemic stroke.

BackgroundPreconditioning methods, which could increase tolerance of brain to subsequent ischemic injuries with a small dose of non-injury stimuli, have gained attention. Capitalizing on noninvasiveness and safety of ultrasound modality, the pulsed transcranial ultrasound stimulation (pTUS) approach may provide a novel treatment for patients with high risk of stroke.ObjectiveThis study's goal was to investigate whether the risk of stroke could be minimized or eliminated by prior exposure to low-intensity, pulsed transcranial ultrasound stimulation (pTUS).MethodsRats were randomly assigned to control (n = 12) and pTUS preconditioning (pTUS-PC) groups (n = 14). The animals in pTUS-PC group were exposed to transcranial ultrasound stimulation before the induction of photothrombotic stroke, whereas control animals were handled identically but without the ultrasound stimulation. Cerebral blood flow was monitored using laser speckle imaging in both groups during stroke induction, as well as 24 and 48 h after stroke, respectively. Also, infarct volumes and edema were measured at 48 h after stroke.ResultspTUS-PC rats had smaller ischemic areas during stroke induction, and 24 and 48 h after the stroke, and smaller infarct volume (1.770 ± 0.169%) than the controls (3.215 ± 0.401%) (p < 0.01). Moreover, the pTUS-PC group experienced lower volume of brain edema than the control group (pTUS-PC rats: 6.658 ± 1.183%; control rats: 12.48 ± 1.386%, p < 0.01).ConclusionThese results support the hypothesis that transcranial ultrasound stimulation applied before photothrombosis could provide neuroprotection by increasing the brain's tolerance to subsequently induced focal ischemic injury.