title: Niacin suppresses the mitogen-activated protein kinase pathway and attenuates brain injury after cardiac arrest in rats.
abstract: OBJECTIVE
  To determine whether niacin attenuates brain injury and improves neurological outcome after cardiac arrest in rats and if its therapeutic benefits are associated with suppression of the mitogen-activated protein kinase pathway.
  
  
  METHODS
  Prospective laboratory study.
  
  
  METHODS
  University laboratory.
  
  
  METHODS
  Male Sprague-Dawley rats (n=77).
  
  
  METHODS
  After 6 minutes of no flow time induced by ventricular fibrillation, cardiopulmonary resuscitation was provided and return of spontaneous circulation was achieved. Animals were then administered vehicle, single low dose (360 mg/kg; at 1 hr postreturn of spontaneous circulation), single high dose (1080 mg/kg; at 1 hr), or repeated low dose of niacin (360 mg/kg/d for 3 d; at 1, 24, and 48 hr) through an orogastric tube.
  
  
  RESULTS
  Neurologic deficit scales were scored at 24 hours, 72 hours, and 7 days postreturn of spontaneous circulation. Single high dose of niacin improved neurologic deficit scales at 48 hours and 7 days, and repeated low dose of niacin improved neurologic deficit scales at 7 days. Then, a separate set of animals were killed at 72 hours postreturn of spontaneous circulation, and brain tissues were harvested. Single high dose and repeated low dose of niacin attenuated cellular apoptosis and neuronal damage in hippocampal cornu ammonis 1 and decreased axonal injury and microglial activation in corpus callosum. They increased nicotinamide adenine dinucleotide, reduced nicotinamide adenine dinucleotide phosphate and reduced glutathione levels, and decreased malondialdehyde level in brain tissues. Furthermore, they suppressed the phosphorylations of p38 and c-Jun N-terminal kinase/stress-activated protein kinase and the cleavage of caspase 3. However, they failed to enhance extracellular signal-regulated kinases 1/2 phosphorylation.
  
  
  CONCLUSIONS
  Single high dose and repeated low dose of niacin attenuated brain injury and improved neurological outcome after cardiac arrest in rats. Their therapeutic benefits were associated with suppressions of the phosphorylations of p38 and c-Jun N-terminal kinase/stress-activated protein kinase and the cleavage of caspase 3.
authors: Department of Emergency Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors: Woon Yong
authors: WY
authors: Kwon
authors: Gil Joon
authors: GJ
authors: Suh
authors: Kyung Su
authors: KS
authors: Kim
authors: Hui Jai
authors: HJ
authors: Lee
authors: Ki Young
authors: KY
authors: Jeong
authors: Young Ho
authors: YH
authors: Kwak
authors: Kyuseok
authors: K
authors: Kim
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D006323:Heart Arrest / Q000150:complications*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D009525:Niacin / Q000008:administration & dosage / Q000494:pharmacology*; D010766:Phosphorylation; D011446:Prospective Studies; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D014665:Vasodilator Agents; D009525:Niacin; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases