Effect of therapeutic ultrasound on brain angiogenesis following intracerebral hemorrhage in rats

Intracerebral hemorrhage (ICH) can produce severe neurological deficits in stroke survivors. However, few effective approaches are available to improve the recovery from ICH. Given that therapeutic ultrasound exposure can enhance on angiogenesis in peripheral tissues, the present study was designed to examine the effects of therapeutic ultrasound exposure on the brain angiogenesis following ICH. To this end, we applied once daily therapeutic ultrasound treatment to rats for 7 consecutive days after intracranial infusion of vehicle (Sham control) or collagenase (ICH). Repeated exposure to the low intensity of therapeutic ultrasound decreased behavioral scores in ICH rats, but not in sham control rats. Such an effect was correlated with an increased number of vessel-like structures and microvessels and PCNA positive cells in vWF-positive blood vessels in perihematomal brain tissues at post-ICH day 7. Furthermore, immunohistochemistry and western blotting results showed that ICH trigged the expression of extracellular matrix (ECM)-related molecules, including collagen Is, III, and IV, as well as integrins αvβ3 and α5β1, and exposure to therapeutic ultrasound increased the expression of these molecules. Therefore, our results indicated that repeated exposure to a low intensity of therapeutic ultrasound can increase the expression of collagen and integrins of ECM-related molecules, promote the formation of a large number of vessel-like structure and capillaries around the hematoma, and accelerate the recovery of neurological function impaired by ICH.