Effect of electroporation on blood-brain barrier

Abstract

The blood-brain barrier (BBB) is a multicellular vascular structure that separates the central nervous system (CNS) from the peripheral blood circulation. It forms the major obstacle for effective drug penetration into the brain, thus limiting extensively the efficacy of systemically administered therapeutic agents for treating brain tumors as well as neurodegenerative diseases. Electroporation (EP)-induced BBB disruption is a novel technique that can be used for delivering high concentrations of therapeutic drugs to specific brain regions. Electroporation is a technique in which intense electric pulses are applied to make the cell membrane transiently porous and increase permeability to ions and macromolecules. When applied to the brain, electroporation can also induce transient BBB disruption. The BBB can either be disrupted without causing irreversible damage to the brain or in combination with irreversible electroporation where BBB disruption surrounds a smaller irreversibly electroporated volume. The treatment can be performed in a minimally invasive manner using a single intracranial electrode or require craniotomy if multiple electrodes are used. It is possible to predict treatment outcome using statistical and computerized models describing the electrical field distribution in the brain. Electroporation-induced localized BBB disruption lasts in the order of 24-48 h. The relatively long duration of the disruption differs from reversible electroporation which only lasts several minutes post treatment. The combination of electroporation-induced BBB disruption with systemic administration of therapeutic agent is suitable for treating primary or metastatic brain tumors as well as localized neurodegenerative diseases.