Survival of cultured hippocampal neurons upon hypoxia: neuroprotective effect of gabapentin Przeżycie hodowli komórek nerwowych hipokampa w warunkach niedotlenienia: neuroprotekcyjny efekt gabapentyny

ABSTRACT Introduction: Gabapentin (GBP) is a novel analogue of GABA used widely in the treatment of epileptic partial seizures and neuropathic pain. GBP blocks Ca2+ channels in neural cell membrane and diminishes excitation of neurons. Such mechanism of action of this drug can predict GBP as a potential neuroprotectant. Aim of the study: To investigate the putative protective effect of GBP against hypoxia-induced neurotoxicity in primary culture of rat hippocampal neurons. Material and methods: An experiment was performed on dissociated hippocampal cultures at seven day in vitro. Cell death was induced by incubation of neural cultures in hypoxic conditions over 24 hours. The cultures (except control) were treated with 30 μM, 100 μM and 300 μM concentrations of GBP to cause a neuroprotective effect. Neuronal injury was assessed by morphometric investigation of death/viable neurons in light microscopy using Trypan blue staining. Results and conclusions: None of the used concentrations of GBP exerted per se a toxic effect on cultured neural cells. Death of one third of neurons was observed in non-treated cultures upon hypoxia. GBP was found to inhibit hypoxia-induced neuronal damage in a dose-dependent manner: in cultures treated with high concentrations of the drug (100 μM and 300 μM), about two-fold higher number of neurons remained viable when compared to non-treated cultures. The results suggest that GBP has promising neuroprotective properties in vitro and prevents hypoxia-induced cell damage in primarily cultured hippocampal neurons