Hypoxia protects against the neurotoxicity of kainic acid

A normobar hypoxia (9% oxygen) of 8 h reduces the neurotoxicity of a subcutaneous injection of 10 mg/kg kainic acid given one week later. Both seizures and degenerative changes, including cell death of hippocampal and cortical neurons are markedly decreased by hypoxia. It is also shown that hypoxia also markedly reduced the extensive depletion of zinc from mossy fiber terminals normally induced by kainic acid. This suggests that a protective mechanism induced by hypoxia may affect the glutamatergic transmission in these synapses and prevent excessive synaptic excitation. The possible involvement of adenosine and/or GABA in this protective mechanism is discussed.