Picture of neon light reading 'Open'

Discover open research at Strathprints as part of International Open Access Week!

23-29 October 2017 is International Open Access Week. The Strathprints institutional repository is a digital archive of Open Access research outputs, all produced by University of Strathclyde researchers.

Explore recent world leading Open Access research content this Open Access Week from across Strathclyde's many research active faculties: Engineering, Science, Humanities, Arts & Social Sciences and Strathclyde Business School.

Explore all Strathclyde Open Access research outputs...

Amphiphilic, tri-block copolymers provide potent, membrane-targeted neuroprotection

Marks, J.D. and Pan, C.Y. and Bushell, T. and Cromie, W. and Lee, R.C. (2001) Amphiphilic, tri-block copolymers provide potent, membrane-targeted neuroprotection. FASEB Journal, 15. pp. 1107-1109. ISSN 0892-6638

Full text not available in this repository. Request a copy from the Strathclyde author

Abstract

Excitatory amino acid receptor activation and reactive oxygen species production are important mediators of neuronal death following acute brain injury and can lead to loss of membrane integrity. Poloxamer 188 (P188) is an amphiphilic, polyethylene-polypropylene-polyethylene copolymer that restores plasma membrane integrity of nonneuronal cells following membrane injury. Here, we demonstrate that P188 provides profound protection of hippocampal and cerebellar neurons following severe excitotoxic and oxidative injury in vitro, through membrane-targeted mechanisms. Widespread death of cultured hippocampal neurons observed 48 h after N-methyl-D-aspartate (NMDA) exposure was prevented by incubation of neurons in P188 following NMDA. P188 provided similar neuroprotection from kainate, menadione, and tert-butyl-hydroperoxide, but not from staurosporine. P188 application did not alter either NMDA receptor function or NMDA-induced [Ca2+]i increases. Whole-cell capacitance measurements revealed that P188 application increased cell surface area, consistent with its insertion into the plasma membrane. Following plasma membrane electroporation, P188 arrested loss of intracellular contents, which demonstrated direct restoration of plasma membrane integrity following physical disruption. Measurements of oxidized C11-BODIPY581/591F fluorescence demonstrated that P188 blocked lipid peroxidation. These observations demonstrate that amphiphilic tri-block copolymers provide strong, membrane-targeted neuroprotection and represent a novel approach to the treatment of acute neuronal injury.