Endogenous GABA attenuates CNS white matter dysfunction following anoxia

摘要: We studied the effects of GABA on anoxia-induced injury in CNS white matter using optic nerves exposed to 60 min anoxia. Injury was assessed by recording pre- and postanoxic compound action potentials (CAPs). (1 microM) significantly increased CAP recovery when applied prior This effect bicuculline (100 insensitive, mimicked baclofen microM), blocked GABA-B antagonists, not selective GABA-A agonists. therefore acted at receptors. High concentrations did influence recovery, possibly indicating receptor desensitization high agonist concentrations. Pertussis toxin (PTX) treatment reduced presence 1 microM control levels, recruitment a G-protein-linked intracellular pathway. Protein kinase C (PKC) activation with 12-myristate 13-acetate (PMA) GABA. Inhibition PKC 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H7) or staurosporine lower levels than under conditions, confirming involvement protective that this receptor/G-protein/PKC pathway might be active conditions. confirmed observation blockade, absence exogenous GABA, postanoxia recovery. Thus, mechanism conditions is due endogenous release. Increasing level extracellular blocking uptake mM nipecotic acid also protected against propose model where release helps limit nerve fiber during anoxia via G-protein/PKC subsequent phosphorylation an unknown target protein.