Hypoxia preconditioning attenuates brain edema associated with kainic acid-induced status epilepticus in rats

Kainic acid (KA)-induced seizures elicit edema associated with necrosis in susceptible brain regions (e.g., piriform cortex and hippocampal CA1 and CA3 regions). To test the hypothesis that hypoxia preconditioning protects against KA-induced edema formation, adult male rats were exposed to a 9% O2, 91% N2 atmosphere for 8 h. KA (14 mg/kg, i.p.) was administered 1, 3, 7, or 14 days later. Regional analysis of edema indicated that hypoxia exposure attenuated edema formation in piriform and frontal cortices and hippocampus when KA was given 1, 3, or 7 days later but not 14 days after hypoxia. Cycloheximide (2 mg/kg s.c.) given 1 h prior to hypoxia prevented the protective effect of hypoxia on KA-induced edema attenuation in the piriform cortex and hippocampus. Thus, hypoxic challenge induces a general adaptive response that protects against the seizure-associated pathophysiology, with no direct relationship to seizure intensity. This response may involve stress-related transcription factors and effector proteins.