Safety Assessments of Electroacupuncture-Mediated Blood–Brain Barrier Opening: An Animal Study

Abstract

The presence of the Blood–Brain barrier (BBB) makes it difficult for therapeutic agents to reach the brain to treat brain diseases. As an emerging treatment, electroacupuncture (EA)-mediated BBB opening can temporarily increase the permeability of the brain blood vessels to increase the concentration of the therapeutic agent in the brain parenchyma, which offers great clinical benefits. Recent studies have suggested that BBB opening with excessive exposure levels may cause tissue/cell damage and short-term behavioral changes. Here, we investigated whether the EA-mediated BBB opening cause serious adverse events in the normal rat brain tissue and motor behavior, such as brain tissue damage, histopathologic alteration, or aggravated behavioral changes. EA was performed on the accupoint GV26 and GV20. Evans Blue Assay (EBA) and fluorescein isothiocyanate (FITC)–dextran Assay were performed to assess the BBB permeability. Immunofluorescence of GFAP-positive cells was marked and Hematoxylin-eosin (HE) Staining was carried out for assessing brain cortex damage. Tunel Assay was conducted to assess cell apoptosis. ELISA was used to measure the contents of TNF-α and IL-1β in brain tissue to explore the inflammatory response. The open field test, balance beam test and Y-Maze test were carried out to assess and neural behaviour. EA can induce an increase in BBB permeability on rats, allowing the macromolecular tracer Evans blue (EB) and Fluorescein Isothiocyanate (FITC)–Dextran to enter the brain. Histological analysis indicated that there was no obvious red blood cell leakage and a cellular apoptotic response in the brain tissue of rats with EA treatment. In addition, EA stimulation at specific parameters did not impair the rats’ motor ability, balance and coordination, and short-term spatial learning and memory. Our results suggest that EA can safely and effectively open the BBB in rats without causing brain damage and behavioral memory impairment.