A single low-energy shockwave pulse opens blood-cerebrospinal fluid barriers and facilitates gastrodin delivery to alleviate epilepsy
Journal
Ultrasonics sonochemistry
Journal Volume
78
Date Issued
2021-10
Author(s)
Kung, Yi
Wen, Tz-Yi
Chen, Moxian
Liao, Wei-Hao
Ao, Lijuan
Abstract
The blood-cerebrospinal fluid barrier (BCSFB) is another gatekeeper between systemic circulation and the central nervous system (CNS), mainly present at the boundary between choroid plexuses and the ventricular system. This study demonstrates BCSFB opening in rats by single pulse of low-energy focused shockwave (FSW, energy flux density 0.03 mJ/mm2, 2 × 106 microbubbles/kg) treatment at lateral ventricle, resulting in significantly elevated cerebrospinal fluid (CSF) concentrations of systemically-administered gastrodin (GTD) (4 times vs. control within 3 hrs) that remained detectable for 24 hrs. The FSW-GTD group had significantly lower Racine's scale (<4) and zero mortality (n = 30) after lithium-pilocarpine-induced epilepsy. Electrophysiological recordings showed decreased epileptiform discharges, and brain section histology revealed reduced inflammation, oxidative stress and apoptosis, when compared with groups without FSW (Racine's scale: 4 ∼ 5; mortality: 26.67 ∼ 36.67%). FSW-mediated BCSFB opening provides a promising alternative for controlled-delivery of therapeutics into the CNS, offering rapid and widespread medication distribution. The technique could by applied in the development of novel therapies for various CNS diseases.
Subjects
Alleviate epilepsy; Blood-cerebrospinal fluid barriers; Gastrodin; Single low-energy shockwave
SDGs
Other Subjects
Blood; Brain; Cerebrospinal fluid; Electrophysiology; Neurology; Shock waves; Alleviate epilepsy; Blood-cerebrospinal fluid-barrier; Central nervous systems; Energy flux density; Gastrodin; Lower energies; Single low-energy shockwave; Single pulse; Systemic circulation; Ventricular systems; Cell death; alkaline phosphatase; chloral hydrate; gastrodin; glial fibrillary acidic protein; lithium chloride; malonaldehyde; pilocarpine; superoxide dismutase; benzyl alcohol derivative; gastrodin; glucoside; adult; animal experiment; animal model; animal tissue; apoptosis; Article; blood cerebrospinal fluid barrier; brain lateral ventricle; choroid plexus; circulation; controlled study; drug delivery system; electrocorticography; electroencephalogram; electrophysiological procedures; epilepsy; epileptic discharge; epileptic patient; feasibility study; histopathology; human; immunohistochemistry; inflammation; male; microbubble; mortality; nonhuman; oxidative stress; rat; seizure score; therapy effect; tonic clonic seizure; videorecording; animal; blood brain barrier; drug effect; metabolism; Animals; Benzyl Alcohols; Blood-Brain Barrier; Choroid Plexus; Epilepsy; Glucosides; Rats
Type
journal article