[Neuroprotective effect of a neurotoxin, 3-nitropropionic acid, against hypoxic damage to the gerbil hippocampus: neuroprotection after the onset of hypoxic depolarization].

Ischemic/hypoxic tolerance induced by a subtoxic dose of neurotoxin, 3-nitropropionic acid(3-NPA), was recently reported as "chemical preconditioning". We previously showed that the neuroprotective effect by chemical preconditioning with 3-NPA was induced by prolonging the delay to hypoxic depolarization (HD) via activating adenosine receptors. In this study, we electrophysiologically assessed whether the protective effect of chemical preconditioning was potent after the onset of HD. An in vitro hippocampal slice model from adult gerbils was used to study the delay to HD during hypoxia and the recovery of synaptic responses after hypoxia. Hypoxia was sustained until a fixed period(8 min) following HD. These responses were examined in control slices and slices pretreated with subtoxic dose of 3-NPA(4 mg/kg) intraperitoneally at 3 hours prior to slice preparation. The delay to hypoxic depolarization in 3-NPA treated slices was significantly prolonged(p < 0.05). The field excitatory postsynaptic potential recovery after a fixed period of hypoxia under HD was also significantly improved in the 3-NPA treated group(48.6 +/- 23.8%) compared with the control group(29.2 +/- 12.2%) (p < 0.05). This finding indicates that chemical preconditioning with 3-NPA induces the neuroprotective effect against hypoxic damage after as well as before the onset of HD to the hippocampus.