Effects of hypoxia preconditioning on expression of metallothionein-1,2 and heme oxygenase-1 before and after kainic acid-induced seizures

Global hypoxia preconditioning provides neuroprotection against a subsequen t, normally damaging challenge. While the mechanistic pathways are unknown, changes in the expression of stress-related proteins are implicated. Hypox ia preconditioning attenuates the brain edema and neuropathology associated with kainic acid-induced status epilepticus in a protein synthesis-depende nt manner when a kainic acid challenge is given up to one week post-precond itioning. Kainic acid initiates a glutamate-driven status epilepticus causi ng a Ca2+ and oxidative stress, resulting in injury to the piriform cortex and hippocampus. Stress-related gene expression [e.g. metallothioneins (MTs ), heme oxygenase-1 (HO-1)] is enhanced during seizures in vulnerable brain areas, (e.g. piriform cortex). This study explores the effects of hypoxia preconditioning on expression of MT-1, MT-2 and HO-1 before and after kaini c acid-induced seizures. Analysis of MT-I, MT-2 and HO-I expression, throug h Western and Northern blotting, indicates that there is a variable pattern of induction and suppression of these two genes following hypoxia precondi tioning alone as well as after kainic acid-induced seizures compared to non -preconditioned animals. These findings suggest that hypoxia preconditionin g induces an adaptive response that prevents kainic acid seizure-associated neuropathology even when robust seizures occur. This may involve a variety of stress-related proteins, working in concert, each with their own indivi dual expression profiles. Induction of this type of neuroprotection pharmac ologically, or through preconditioning, will provide a better understanding of the stress response in brain.