PMID- 12142569 OWN - NLM STAT- MEDLINE DCOM- 20020809 LR - 20091119 IS - 0271-678X (Print) IS - 0271-678X (Linking) VI - 22 IP - 7 DP - 2002 Jul TI - Hypothermic reperfusion after cardiac arrest augments brain-derived neurotrophic factor activation. PG - 843-51 AB - Induction of mild hypothermia improves neurologic outcome after global cerebral ischemia. This study measured levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in hippocampal tissue of rats after resuscitation from 8 minutes of normothermic, asphyxial cardiac arrest. After resuscitation, rats were maintained either at normal temperature (37 degrees C) or cooled to mild hypothermia (33 degrees C, beginning 60 minutes after resuscitation). After 12 or 24 hours, neurotrophin levels in hippocampus were measured by immunoblotting. Ischemia and reperfusion increased hippocampal levels of BDNF. Induction of hypothermia during reperfusion potentiated the increase in BDNF after 24 hours, but not after 12 hours. Levels of NGF were not increased by postresuscitation hypothermia. Hypothermia also increased tissue levels and tyrosine phosphorylation of TrkB, the receptor for BDNF. Increased BDNF levels were correlated with activation of the extracellularly regulated kinase (ERK), a downstream element in the signal transduction cascade induced by BDNF. In contrast to the many deleterious processes during ischemia and reperfusion that are inhibited by induced hypothermia, increasing BDNF levels is a potentially restorative process that is augmented. Increased activation of BDNF signaling is a possible mechanism by which mild hypothermia is able to reduce the neuronal damage typically occurring after cardiac arrest. FAU - D'Cruz, Brian J AU - D'Cruz BJ AD - Department of Emergency Medicine, University of Pittsburgh, Pennsylvania 15213, USA. FAU - Fertig, Kristofer C AU - Fertig KC FAU - Filiano, Anthony J AU - Filiano AJ FAU - Hicks, Shawn D AU - Hicks SD FAU - DeFranco, Donald B AU - DeFranco DB FAU - Callaway, Clifton W AU - Callaway CW LA - eng GR - NS02112/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Cereb Blood Flow Metab JT - Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism JID - 8112566 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 21820-51-9 (Phosphotyrosine) RN - 9061-61-4 (Nerve Growth Factor) RN - EC 2.7.10.1 (Receptor, trkB) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) SB - IM MH - Animals MH - Asphyxia MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Enzyme Activation MH - Heart Arrest/etiology/*metabolism/pathology MH - *Hypothermia, Induced MH - Immunoblotting MH - Immunosorbent Techniques MH - Ischemic Attack, Transient/*metabolism MH - Kinetics MH - Male MH - Mitogen-Activated Protein Kinases/metabolism MH - Nerve Growth Factor/metabolism MH - Neurons/pathology MH - Phosphorylation MH - Phosphotyrosine/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Receptor, trkB/metabolism MH - *Reperfusion MH - Signal Transduction EDAT- 2002/07/27 10:00 MHDA- 2002/08/10 10:01 CRDT- 2002/07/27 10:00 PHST- 2002/07/27 10:00 [pubmed] PHST- 2002/08/10 10:01 [medline] PHST- 2002/07/27 10:00 [entrez] AID - 10.1097/00004647-200207000-00009 [doi] PST - ppublish SO - J Cereb Blood Flow Metab. 2002 Jul;22(7):843-51. doi: 10.1097/00004647-200207000-00009.