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Abstract: Assays on “ex vivo” sections of rat hippocampus and rat cerebral cortex, subjected to oxygen and glucose deprivation (OGD) and a three-hour reperfusion-like (RL) recovery, were performed in the presence of either GABA or the GABAA receptor binding site antagonist, bicuculline. Lactate dehydrogenase (LDH) and propidium iodide were used to quantify cell mortality. We also measured, using real-time quantitative polymerase chain reaction (qPCR), the early transcriptional response of a number of genes of the glutamatergic and GABAergic systems. Specifically, glial pre- and post-synaptic glutamatergic transporters (namely GLAST1a, EAAC-1, GLT-1 and VGLUT1), three GABAA receptor subunits (α1, β2 and γ2), and the GABAergic presynaptic marker, glutamic acid decarboxylase (GAD65), were studied. Mortality assays revealed that GABAA receptor chloride channels play an important role in the neuroprotective effect of GABA in the cerebral cortex, but have a much smaller effect in the hippocampus. We also found that GABA reverses the OGD-dependent decrease in GABAA receptor transcript levels, as well as mRNA levels of the membrane and vesicular glutamate transporter genes. Based on the markers used, we conclude that OGD results in differential responses in the GABAergic presynaptic and postsynaptic systems. [Copyright &y& Elsevier]

Stroke is one of the major causes of death and disability worldwide. The major type of stroke is an ischaemic one, which is caused by a blockage that interrupts blood flow to the brain. There are currently very few pharmacological strategies to reduce the damage and social burden triggered by this pathology. The harm caused by the interruption of blood flow to the brain unfolds in the subsequent hours and days, so it is critical to identify new therapeutic targets that could reduce neuronal death associated with the spread of the damage. Here, we review some of the key molecular mechanisms involved in the progression of neuronal death, focusing on some new and promising studies. In particular, we focus on the potential of the chloride co-transporter (CCC) family of proteins, mediators of the GABAergic response, both during the early and later stages of stroke, to promote neuroprotection and recovery. Different studies of CCCs during the chronic and recovery phases post-stroke reveal the importance of timing when considering CCCs as potential neuroprotective and/or neuromodulator targets. The molecular regulatory mechanisms of the two main neuronal CCCs, NKCC1 and KCC2, are further discussed as an indirect approach for promoting neuroprotection and neurorehabilitation following an ischaemic insult. Finally, we mention the likely importance of combining different strategies in order to achieve more effective therapies., (© 2016 International Society for Neurochemistry.)