Picrotoxin (GABAA receptor antagonist) shows a protective role in brain injury during neonatal development

Abstract

GABAA-receptor antagonist picrotoxin has been shown to have actions upon brain injury dur-ing neonatal development. The significance of the expression of GABAA-receptors in devel-oping brain specifically white matter during injury has not been completely examined. As well previous studies have concentrated upon brief periods of receptor activation and later points in development. For this paper work, the injury capacity of a standard 90-min period of both oxygen-glucose deprivation (OGD) and artificial cerebrospinal fluid (aCSF) co-perfused with a GABAA-R antagonist were examined using electrophysiology and ultrastruc-tural analysis techniques of P0 rat optic nerves (RONs) (a model of non-myelinated brain white matter). The result reveals the potential role of inhibitory other than excitatory neuro-transmitters mediated injury in young brain in early points of development. It shows that GABAA-R block both increased compound action potential (CAP) under control conditions, and protected the RONs from OGD-induced injury. The protective effects of 100μM GABAA-R antagonist against OGD-induced axonal injury in P0-RONs using electrophysio-logical technique is consistent with ultra-micrograph data presented here showing protective effects against OGD-induced axonal and glial injury in P0-RONs. The results of both electro-physiology and microscopy are consistent with a potential role of GABAA-R-mediated injury in neonatal brain. This indicates the protective role of the GABAA-R antagonist against is-chaemic injury in non-myelinated brain.