Poloxamer 188 reduces axonal beading following mechanical trauma to cultured neurons.

Abstract

Diffuse axonal injury (DAI), a major component of traumatic brain injury, is a progressive event that may lead to secondary neuronal death. DAI is thought to be initiated by mechanically-induced increases in axolemmal permeability resulting in disruption of the cytoskeleton and blockade of axonal transport. We report an in vitro model that mimics important features of DAI observed in vivo. We induced fluid shear stress injury (FSSI) on cultured primary chick forebrain neurons and characterized the resulting structural and morphological changes. In addition, we tested the post-injury effect of Poloxamer 188 (P188), a tri-block co-polymer that is known to promote resealing membrane pores. We found that FSSI induces axonal beading, the "hallmark" morphology of DAI. Furthermore, beads co-localized with microtubule disruption, also characteristic of DAI. P188 reduced axonal beading to control levels indicating that axolemma integrity is an excellent target for therapeutic interventions.