Sodium pyruvate reduces hypoxic-ischemic injury to neonatal rat brain

Rui Pan, Zhihui Rong, Yun She, Yuan Cao, Li Wen Chang, Wei Hua Lee

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

BackgroundNeonatal hypoxia-ischemia (HI) remains a major cause of severe brain damage and is often associated with high mortality and lifelong disability. Immature brains are extremely sensitive to HI, shown as prolonged mitochondrial neuronal death. Sodium pyruvate (SP), a substrate of the tricarboxylic acid cycle and an extracellular antioxidant, has been considered as a potential treatment for hypoxic-ischemic encephalopathy, but its effects have not been evaluated in appropriate animal models for hypoxic-ischemic encephalopathy.MethodsThis investigation used primary cortical neuron cultures derived from neonatal rats subjected to oxygen and glucose deprivation (OGD) and a well-established neonatal rat HI model.ResultsHI caused brain tissue loss and impaired sensorimotor function and spatial memory whereas SP significantly reduced brain damage and improved neurological performance. These neuroprotective effects of SP are likely the result of improved cerebral metabolism as demonstrated by maintaining adenosine triphosphate (ATP) levels and preventing an increase in intracellular reactive oxygen species (ROS) levels. SP treatment also decreased levels of Bax, a death signal for immature neurons, blocked caspase-3 activation, and activated a key survival signaling kinase, Akt, both in vitro and in vivo.ConclusionSP protected neonatal brain from hypoxic-ischemic injury through maintaining cerebral metabolism and mitochondrial function.

Original languageEnglish (US)
Pages (from-to)479-489
Number of pages11
JournalPediatric Research
Volume72
Issue number5
DOIs
StatePublished - Nov 1 2012

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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    Pan, R., Rong, Z., She, Y., Cao, Y., Chang, L. W., & Lee, W. H. (2012). Sodium pyruvate reduces hypoxic-ischemic injury to neonatal rat brain. Pediatric Research, 72(5), 479-489. https://doi.org/10.1038/pr.2012.107