PMID- 16289484
OWN - NLM
STAT- MEDLINE
DCOM- 20060307
LR  - 20091119
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 1064
IP  - 1-2
DP  - 2005 Dec 7
TI  - Hypothermia and ERK activation after cardiac arrest.
PG  - 108-18
AB  - Mild hypothermia improves survival and neurological outcome after cardiac arrest, 
      as well as increasing activation of the extracellular-signal-regulated kinase 
      (ERK) in hippocampus. ERK signaling is involved in neuronal growth and survival. 
      We tested the hypothesis that the beneficial effects of hypothermia required ERK 
      activation. ERK activation was measured by immunoblotting with 
      phosphorylation-specific antibodies. Rats (n = 8 per group) underwent 8 min of 
      asphyxial cardiac arrest and were resuscitated with chest compressions, 
      ventilation, epinephrine and bicarbonate. At 30 min after resuscitation, vehicle 
      (50% saline:50% DMSO) or the ERK kinase inhibitor U0126 (100 microg) was infused 
      into the lateral ventricle. Cranial temperature was kept at either 33 degrees C 
      (hypothermia) or 37 degrees C (normothermia) between 1 and 24 h. Neurological 
      function was assessed daily for 14 days. Surviving neurons were counted in the 
      hippocampus. A dose of 100 mug U0126 inhibited ERK bilaterally for 12 to 24 h and 
      decreased phosphorylation of the ERK substrates ATF-2 and CREB. As in previous 
      studies, hypothermia improved survival, neurological and histological outcome 
      after cardiac arrest. However, survival, neurological score and histology did not 
      differ between U0126 and vehicle-treated rats after cardiac arrest. Therefore, a 
      dose of U0126 sufficient to inhibit biochemical markers of ERK signaling in 
      hippocampus does not alter the beneficial effects of hypothermia induced after 
      resuscitation in rats and did not affect recovery of normothermia-treated rats. 
      These results suggest that hypothermia-induced improvement in outcomes does not 
      require ERK activation.
FAU - D'Cruz, Brian J
AU  - D'Cruz BJ
AD  - Department of Emergency Medicine, 230 McKee Place, Suite 400, Pittsburgh, PA 
      15213, USA.
FAU - Logue, Eric S
AU  - Logue ES
FAU - Falke, Eric
AU  - Falke E
FAU - DeFranco, Donald B
AU  - DeFranco DB
FAU - Callaway, Clifton W
AU  - Callaway CW
LA  - eng
GR  - K02 NS002112/NS/NINDS NIH HHS/United States
GR  - R01 NS46073/NS/NINDS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20051114
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Butadienes)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Nitriles)
RN  - 0 (U 0126)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Animals
MH  - Asphyxia/complications/enzymology/therapy
MH  - Body Temperature
MH  - Brain Damage, Chronic/enzymology/etiology/prevention & control
MH  - Butadienes/administration & dosage
MH  - Cell Survival/physiology
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Activation
MH  - Enzyme Inhibitors/administration & dosage
MH  - Extracellular Signal-Regulated MAP Kinases/*metabolism
MH  - Heart Arrest/complications/*enzymology/*therapy
MH  - Hippocampus/*enzymology
MH  - Hypothermia/complications/*enzymology
MH  - *Hypothermia, Induced
MH  - Injections, Intraventricular
MH  - Male
MH  - Nitriles/administration & dosage
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Resuscitation
MH  - Signal Transduction/physiology
EDAT- 2005/11/18 09:00
MHDA- 2006/03/08 09:00
CRDT- 2005/11/18 09:00
PHST- 2005/07/25 00:00 [received]
PHST- 2005/09/21 00:00 [revised]
PHST- 2005/09/25 00:00 [accepted]
PHST- 2005/11/18 09:00 [pubmed]
PHST- 2006/03/08 09:00 [medline]
PHST- 2005/11/18 09:00 [entrez]
AID - S0006-8993(05)01351-X [pii]
AID - 10.1016/j.brainres.2005.09.052 [doi]
PST - ppublish
SO  - Brain Res. 2005 Dec 7;1064(1-2):108-18. doi: 10.1016/j.brainres.2005.09.052. Epub 
      2005 Nov 14.