Ultrasound-induced blood–brain barrier opening and selenium-nanoparticle injection lower seizure activity: A mouse model of temporal lobe epilepsy

BACKGROUND: Given the limitations of current treatment options for drug-resistant mesial temporal lobe epilepsy (MTLE), the development of novel, nonablative and minimally invasive surgical techniques is essential. OBJECTIVE AND METHODS: In this study, low-intensity pulsed ultrasound (LIPU)- and microbubble-induced (henceforth LIPU) blood-brain barrier (BBB) opening combined with selenium-nanoparticle (SeNP) intravenous injection in a mouse model of mesial temporal lobe optimized the latter's bioavailability in the brain epileptic tissue of the kainic acid (KA) mouse model of MTLE. We aimed to assess the safety and antiepileptic potential of LIPU-enhanced SeNP delivery against KA-induced seizures using long-term intracranial electroencephalogram video recordings and evaluating neuroinflammation, astrogliosis, neuronal apoptosis and neurogenesis in the hippocampal tissues of mice. RESULTS: First, we established that SeNP intravenous injection combined with LIPU-induced BBB disruption was the most effective method to achieve high and sustained selenium levels in the brain. The safety of this treatment was demonstrated after three treatment sessions, 1-week apart, with no adverse effects observed. Our results further showed a significantly lower frequency of epileptic seizures (-90 %, P = 0.001) in KA mice treated with LIPU + SeNPs compared to sham-treated controls. Short- and long-term histological changes were seen after that combined regimen, including less aberrant neurogenesis in the hippocampus hilum, less neuronal death throughout the hippocampus and less hippocampal microglial activation, which might collectively contribute to the observed antiseizure effect. CONCLUSION: SeNP injection combined with LIPU-induced BBB disruption demonstrated potential as a promising approach to reduce seizure activity in MTLE; however, statistical comparison did not conclusively establish superiority over SeNPs alone. Further investigations are necessary to consider translational studies in humans.