Focused Ultrasound Alleviates Ventriculomegaly and Behavioral Impairment in a Hydrocephalus Model

Abstract

Purpose Hydrocephalus is a condition characterized by the abnormal accumulation of cerebrospinal fluid (CSF) in the brain’s ventricles, leading to difficulties with walking, urinary incontinence, and cognitive impairment. Currently, the most common treatment involves the invasive surgical drainage of CSF. Alternatively, recent studies have reported non-invasive methods to facilitate CSF circulation in the brain using focused ultrasound (FUS). The purpose of this study is to explore the potential of FUS as a noninvasive treatment for hydrocephalus, with an emphasis on improving walking and cognitive function while preventing ventricular enlargement.

Materials & Methods We used an 8-week-old male C57BL/6J mouse model of hydrocephalus caused by kaolin. On days 7, 10, and 13 post-hydrocephalus induction, 500-kHz FUS sonication was delivered to the hypothalamus and nasopharynx at 5 W/cm2 Isppa for 30 minutes, with a 10% duty cycle and 1-Hz pulse repetition frequency. The Y-maze test was used to evaluate spatial memory, and the horizontal grid test was used to assess motor behavior. Using H&E staining, changes in ventricle size were analyzed.

Results Compared to hydrocephalus mice that were not treated, FUS-treated hydrocephalus mice had significant improvements in hang time, total steps, and successful steps in the horizontal grid test. In the Y-maze test, spontaneous alternation significantly increased in the FUS-treated hydrocephalus mice, which was decreased in hydrocephalus mice compared to the control mice. The hydrocephalus mice exhibited pronounced ventriculomegaly, but the FUS-treated hydrocephalus mice demonstrated noticeably less enlargement.

Conclusion This study suggests that FUS, a non-invasive procedure that facilitates CSF efflux, could be employed to prevent the progression of hydrocephalus. These findings may lead to the development of novel therapeutic strategies, although further research into the mechanism of action is needed.