Pulsed Focused Ultrasound Reduces Hippocampal Volume Loss and Improves Behavioral Performance in the Kainic Acid Rat Model of Epilepsy

Focused ultrasound (FUS) has the potential to modulate regional brain excitability and possibly aid seizure control; however, effects on behavior of FUS used as a seizure therapy are unknown. This study explores behavioral effects and hippocampal restoration induced by pulsed FUS in a kainic acid (KA) animal model of temporal lobe epilepsy. Twenty-nine male Sprague–Dawley rats were observed for 20 weeks with anatomical magnetic resonance imaging (MRI) and behavioral performance evaluations, comprising measures of anxiety, limb usage, sociability, and memory. FUS targeted to the right hippocampus was given 9 and 14 weeks after KA was delivered to the right amygdala. Ultrasound pulsations were delivered with the acoustic settings of 0.25 of mechanical index, 0.5 W/cm(2) of intensity spatial peak temporal average (I(SPTA)), 100 Hz of pulse repetition frequency, and 30% of duty cycle, during three consecutive pulse trains of 10 min separated by 5-min rests. Controls included normal animals with sham injections and KA-exposed animals without FUS exposure. Longitudinal MRI observations showed that FUS substantially protected hippocampal and striatal structures from KA-induced atrophy. KA alone increased anxiety, impaired contralateral limb usage, and reduced sociability and learning. Two courses of FUS sonications partially ameliorated these impairments by enhancing exploring and learning, balancing limb usage, and increasing social interaction. The histology results indicated that two sonications enhanced neuroprotection effect and decreased the inflammation markers induced by KA. This study supports existence of both neuroprotective and beneficial behavioral effects from low-intensity pulsed ultrasound in the KA animal model of epilepsy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13311-023-01363-7.