title: Sodium pyruvate reduces hypoxic-ischemic injury to neonatal rat brain.
abstract: BACKGROUND
  Neonatal 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.
  
  
  METHODS
  This 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.
  
  
  RESULTS
  HI 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.
  
  
  CONCLUSIONS
  SP protected neonatal brain from hypoxic-ischemic injury through maintaining cerebral metabolism and mitochondrial function.
authors.affiliation: Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Pan
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Rong
authors.forename: Yun
authors.initials: Y
authors.lastname: She
authors.forename: Yuan
authors.initials: Y
authors.lastname: Cao
authors.forename: Li-Wen
authors.initials: LW
authors.lastname: Chang
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Lee
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D019610:Cytoprotection; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects; D004789:Enzyme Activation; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control* / Q000523:psychology; D008568:Memory / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011773:Pyruvates / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D055139:Sensory Gating / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494828:Bax protein, rat; D018696:Neuroprotective Agents; D011773:Pyruvates; D051028:bcl-2-Associated X Protein; D000255:Adenosine Triphosphate; D051057:Proto-Oncogene Proteins c-akt; C505410:Casp3 protein, rat; D053148:Caspase 3