Neuroprotective effect of low-intensity transcranial ultrasound stimulation in endothelin-1-induced middle cerebral artery occlusion in rats

Abstract

Background: Ischemic stroke is one of the leading causes of death and disability worldwide. Low-intensity transcranial ultrasound stimulation (LITUS) is a promising neuroprotective treatment for ischemic stroke. Diffusion-weighted imaging (DWI) can be highly sensitive in the detection of ischemic brain injury. Relative apparent diffusion coefficient (rADC) values can be used to evaluate the effect of LITUS on ischemic stroke.

Purpose: The aim of this study was to determine the neuroprotective effect of LITUS at different time points using endothelin-1-induced middle cerebral artery occlusion in rats as a model of ischemic stroke.

Methods: Endothelin-1 (ET-1) was injected into the cerebral parenchyma near the middle cerebral artery, which induced focal, reversible, low-flow ischemia in rats. After occlusion of the middle cerebral artery for 30 min, 120 min, and 240 min, LITUS stimulation was used respectively. DWI was performed at 1, 3, 6, 12, 18, 24, 48, and 72 h after ischemia using a 3 T scanner. The rADC values were calculated, and functional outcomes assessed using neurobehavioral scores after ischemia. Nissl staining and estimation of Na⁺-K⁺-ATPase activity were used to assess the neuropathology after completing the last Magnetic Resonance Imaging (MRI) examination.

Results: Endothelin-1-induced occlusion of the middle cerebral artery resulted in significant dysfunction and neuronal damage in rats. Rats that received LITUS exhibited reduced damage of the affected brain tissue after cerebral ischemia. The greatest protective effect was found when LITUS stimulation occurred 30 min after cerebral ischemia.

Conclusions: Imaging, behavioral, and histological results suggested that LITUS stimulation after an ischemic stroke produced significant neuroprotective effects.

Keywords: Focal cerebral ischemia; Low-intensity transcranial ultrasound stimulation; Neuroprotection; Readout-segmented echo-planar diffusion-weighted imaging; Relative apparent diffusion coefficient.