“Short-Chain Alkylglycerols' Acute Impact on the Blood-Brain Barrier Characteristics of Cultured Brain Endothelial Cells”

Abstract

Patients with brain tumors cannot receive effective treatment because of the blood-brain barrier's (BBB) restriction on medicine penetration into the brain. Short-chain alkylglycerols (AGs) injected intraarterially open the blood-brain barrier (BBB) and enhance molecular transport to the mouse brain parenchyma in vivo. It is yet unknown what mechanism AG uses to modify BBB permeability. Here, we have examined how cultured brain microvascular endothelial cells' barrier characteristics are affected by AGs. Using an in vitro BBB model made up of primary cultures of rat brain endothelial cells co-cultured with rat cerebral glial cells, the effects of two AGs, 1-O-pentylglycerol and 2-O-hexyldiglycerol, were investigated. Claudin-claudin trans-interactions, immunostaining for junctional proteins, freeze-fracture electron microscopy, and functional assays were used to assess the integrity of the paracellular, tight junction-based permeation route AG therapy for five minutes altered BBB permeability for fluorescein and reversibly decreased trans endothelial electrical resistance, along with alterations in cell shape and β-catenin and claudin-5 immunostaining. Neither the trans-interaction of claudin-5 nor the inter-endothelial tight junction strand complexity changed in tandem with these transient modifications .The short-lived, reversible increase in brain endothelial paracellular permeability caused by AG did not impact the intricacy of tight junction strands. The involvement of the cytoskeleton in the action of AGs is indicated by changes in cell shape and redistribution of junctional proteins. These findings corroborate findings from rodent in vivo research that described AGs as adjuvants that temporarily breach the blood-brain barrier.