Hypothermia and ERK activation after cardiac arrest.
Brain Res
; 1064(1-2): 108-18, 2005 Dec 07.
Article
en En
| MEDLINE
| ID: mdl-16289484
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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Quinasas MAP Reguladas por Señal Extracelular
/
Paro Cardíaco
/
Hipocampo
/
Hipotermia
/
Hipotermia Inducida
Tipo de estudio:
Etiology_studies
Límite:
Animals
Idioma:
En
Revista:
Brain Res
Año:
2005
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Países Bajos