title: Neuroprotective effect of pyruvate and oxaloacetate during pilocarpine induced status epilepticus in rats.
abstract: Recent research data have shown that systemic administration of pyruvate and oxaloacetate causes an increased brain-to-blood glutamate efflux. Since increased release of glutamate during epileptic seizures can lead to excitotoxicity and neuronal cell death, we tested the hypothesis that glutamate scavenging mediated by pyruvate and oxaloacetate systemic administration could have a neuroprotective effect in rats subjected to status epilepticus (SE). SE was induced by a single dose of pilocarpine (350mg/kgi.p.). Thirty minutes after SE onset, a single dose of pyruvate (250mg/kgi.p.), oxaloacetate (1.4mg/kgi.p.), or both substances was administrated. Acute neuronal loss in hippocampal regions CA1 and hilus was quantitatively determined five hours after SE onset, using the optical fractionator method for stereological cell counting. Apoptotic cascade in the hippocampus was also investigated seven days after SE using caspase-1 and -3 activity assays. SE-induced neuronal loss in CA1 was completely prevented in rats treated with pyruvate plus oxaloacetate. The SE-induced caspase-1 activation was significantly reduced when rats were treated with oxaloacetate or pyruvate plus oxaloacetate. The treatment with pyruvate and oxaloacetate caused a neuroprotective effect in rats subjected to pilocarpine-induced SE.
authors.affiliation: Department of Neurology and Neurosurgery - UNIFESP São Paulo, Brazil.
authors.forename: Andrezza Sossai Rodrigues
authors.initials: AS
authors.lastname: Carvalho
authors.forename: Laila Brito
authors.initials: LB
authors.lastname: Torres
authors.forename: Daniele Suzete
authors.initials: DS
authors.lastname: Persike
authors.forename: Maria José Silva
authors.initials: MJ
authors.lastname: Fernandes
authors.forename: Debora
authors.initials: D
authors.lastname: Amado
authors.forename: Maria da Graça
authors.initials: Mda G
authors.lastname: Naffah-Mazzacoratti
authors.forename: Esper Abrão
authors.initials: EA
authors.lastname: Cavalheiro
authors.forename: Alexandre Valotta
authors.initials: AV
authors.lastname: da Silva
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D008297:Male; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000209:etiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D062907:Oxaloacetic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D019289:Pyruvic Acid / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013226:Status Epilepticus / Q000139:chemically induced / Q000150:complications / Q000517:prevention & control*
chemical_list: D018696:Neuroprotective Agents; D062907:Oxaloacetic Acid; D019289:Pyruvic Acid