Pyruvate protects against kainate-induced epileptic brain damage in rats.
Although the majority of epileptic seizures can be effectively controlled with antiepileptic drugs and/or surgery, a significant number progress to status epilepticus of sufficient duration to cause permanent brain damage. Combined treatment with antiepileptic drugs and neuroprotective agents, however, may help protect these individuals from permanent brain damage. Since toxicity induced by endogenous zinc contributes to epileptic brain injury, and since pyruvate is effective in reducing zinc-triggered neuronal death in cortical culture as well as ischemic neuronal death in vivo, we examined whether systemic pyruvate administration reduces seizure-induced brain damage. Na pyruvate (500 mg/kg) or osmolarity-matched saline (265 mg/kg NaCl, i.p.) were given to adult SD rats 30 or 150 min after 10 mg/kg kainite injection (i.p.), and there was no significant difference in the time course or severity of seizures between these groups. Zinc accumulation in neuronal cell bodies in the hippocampus, however, was much lower in the pyruvate than in the saline group. There was a close correlation between zinc accumulation and cell death, as assessed by acid-fuchsin and TUNEL staining. Pyruvate treatment markedly reduced neuronal death in the hippocampus, neocortex and thalamus. Pyruvate increased HSP-70 expression in hippocampal neurons. These results suggest that pyruvate, a natural glucose metabolite, may be useful as adjunct treatment in status epilepticus to reduce permanent brain damage.
Kim
Tae-Youn
TY
Neural Injury Research Lab, University of Ulsan College of Medicine, Seoul 138-736, Korea.
Yi
Jung-Sun
JS
Chung
Sun-Ju
SJ
Kim
Dong-Kyu
DK
Byun
Hyae-Ran
HR
Lee
Joo-Yong
JY
Koh
Jae-Young
JY
D000818:Animals; D001925:Brain Damage, Chronic / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control*; D016923:Cell Death / Q000187:drug effects; D004827:Epilepsy / Q000139:chemically induced / Q000150:complications* / Q000503:physiopathology; D018690:Excitatory Amino Acid Agonists; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology; D007608:Kainic Acid; D008297:Male; D019579:Neocortex / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism; D019289:Pyruvic Acid / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D013788:Thalamus / Q000503:physiopathology; D015032:Zinc / Q000037:antagonists & inhibitors
D018690:Excitatory Amino Acid Agonists; D018840:HSP70 Heat-Shock Proteins; D019289:Pyruvic Acid; D015032:Zinc; D007608:Kainic Acid