Ethyl pyruvate attenuates kainic acid‐induced neuronal cell death in the mouse hippocampus

Abstract

Recent studies have shown that ethyl pyruvate (EP) acts as an anti-inflammatory molecule in several cell lines including RAW264.7 macrophages. However, the potential therapeutic value of EP for the treatment of the pathologic brain has not been investigated fully. In the present study, we examined whether EP has a beneficial effect on KA-induced neuronal cell death. Intracerebroventricular (i.c.v.) injection of 0.94 nmol (0.2 mug) of KA produced typical neuronal cell death in the CA1 and CA3 pyramidal layers of the hippocampus, and the systemic administration of EP significantly attenuated KA-induced neuronal cell death in these regions. Ethyl pyruvate was found to exert a protective effect when it was injected as late as 12 hr after KA-injection. Moreover, this EP-induced neuroprotection was accompanied by reduced levels of reactive gliosis and COX-2, IL-1beta, and TNF-alpha in the hippocampus. In addition, in passive avoidance tests, KA-induced memory impairment was improved markedly by EP. These results suggest that EP has a therapeutic potential for suppressing KA-induced pathogenesis in the brain.

Effects of ethyl pyruvate administration on female rats? pyramidal cells of cornu ammonis after brain ischemia: a stereological and histopathological study *

“…While some of these studies support our finding that EP has no effect on ischemia, others maintain that EP has a neuroprotective effect in ischemia induced in the CNS (16,35,36). Cho et al (35) reported in a study on mice that EP reduced cell death in the hippocampus. In a study on rats, Moro and Sutton (36) reported a decrease in dead cell numbers in the hippocampus of animals in the group administered EP and that neuronal tissue loss also decreased in line with this.…”

“…That study investigated pyramidal neuron deaths in the CA1 and CA3 regions of the hippocampus by the application of kainic acid by the intracerebroventricular route and by the administration of EP 12 h after the injection of kainic acid. At the end of the study, EP was seen to reduce cell deaths in the hippocampus (35). In a study on rats, Moro and Sutton (36) investigated the effects of sodium pyruvate (SP) and EP administered after head trauma.…”

Are nociceptin(1‐13)NH2and its structural analogue [ORN9]nociceptin(1‐13)NH2able to affect brain antioxidant status in control and kainic acid‐treated rats?

“…[36][37][38] Upon binding to non-NMDA glutamate receptors, KA provokes depolarization of neurons followed by severe status epilepticus, neurodegeneration, memory loss, neuronal cell death. [39][40] The possible role of NMDA and non-NMDA receptors in the regulation of neurotoxic responses (lethality, memory loss, hippocampal cell death, signal transduction systems), stimulated by KA was discussed by Lee et al 41 The neuronal degeneration after KA administration is generally accepted to be associated with a depletion of ATP and accumulation of [Ca 2þ ] i.…”

Neuroprotective Effect of Visnagin on Kainic Acid-induced Neuronal Cell Death in the Mice Hippocampus

“…It appears that khellin extracts have some antimicrobial activity; this might be attributable to both the khellin and visnagin constituents, which both seem to have antifungal, antibacterial, and antiviral activity [25]. In addition, several reports have demonstrated that drugs or compounds having an anti-inflammatory effect can show a neuroprotective effect [4,26,27]. Thus, we examined the effect of visnagin on proinflammatory mediators expression induced by KA.…”