Pharmacological management of GABAergic neurons survival in ischemic conditions: the role of a novel hydroxypyridine compound

Introduction. Increasing the survival of neurons in the perinecrotic zone of the brain is a promising strategy in the comprehensive treatment of ischemic stroke.

Aim. To study some molecular mechanisms of hydroxypyridine derivative 3-EA to increase survival of cerebral GABAergic neurons under ischemia-like conditions.

Materials and methods. The cell-protective property of the novel hydroxypyridine compound 3-EA was compared with that of nimodipine. A series of experiments were conducted on 7–9 DIV rat hippocampal neuroglial cell culture containing GABAergic neurons expressing the calcium-binding proteins calbindin and parvalbumin under ischemia-like conditions. Neuron survival was determined using a cytochemical reaction with propidium iodide, and calcium signaling was studied by assessment of fluorescence signal emitted by cells loaded with Fura-2.

Results and discussion. 1 mM 3-EA increased the survival rate of rat brain GABAergic neurons expressing calcium-binding proteins by 25 % (p = 0.001), and was comparable to the reference drug nimodipine. The compound induced an average 2.5-fold suppression of intracellular calcium concentrations by 40 minutes after the ischemia-like environment onset.

Conclusion. The 3-hydroxypyridine compound 3-EA exhibited cell-protective properties and preserved the population of GABAergic neurons containing calbindin and parvalbumin by suppressing glutamatergic excitotoxicity and calcium influx into the cell cytosol. This compound may be considered a potential drug candidate.

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