Regulated hypothermia reduces brain oxidative stress after hypoxic-ischemia.
Regulated hypothermia produces a decrease in core temperature by lowering the brain's temperature set-point while maintaining thermoregulation at that lower set point. In contrast, forced hypothermia lowers core temperature by overwhelming the body's capacity to thermoregulate, but does not change the set-point. Regulated hypothermia has been shown to be cerebral protective in hibernating mammals. The effect of regulated hypothermia on the brain during reperfusion from hypoxic-ischemia has not been well studied. We induced regulated hypothermia with a neurotensin analogue (NT77) to determine whether it could reduce oxidative stress in the brain during reperfusion from asphyxial cardiac arrest (ACA) in rats. Mild hypothermia (32-34 degrees C) was induced by brief (4 h) external cooling (BC), NT77 or prolonged external cooling (24 h) (PC) 30 min after resuscitation from 8 min of ACA in rats. Malondialdehyde (MDA) levels in the brain were measured during reperfusion to quantitate oxidative stress.


RESULTS
MDA levels in the hippocampus were elevated at 16 h of normothermic reperfusion versus 48 h with BC reperfusion. There was no increase in hippocampal MDA levels in the NT77 and PC groups at 24-72 h of reperfusion. Regulated hypothermia induced by NT77 reduced oxidative stress in the hippocampus during reperfusion from hypoxic-ischemia in comparison to forced brief external cooling of the same duration. In addition, the duration of external cooling after resuscitation also alters oxidative stress in the brain during reperfusion.
Katz
Laurence M
LM
Carolina Resuscitation Research Group, Department of Emergency Medicine, University of North Carolina School of Medicine, Neurosciences Hospital, Ground Floor, CB 7594 101 Manning Drive, Chapel Hill, NC 27517, USA. lkatz@med.unc.edu
Young
Amanda S
AS
Frank
Jonathan E
JE
Wang
Yuanfan
Y
Park
Kyunam
K
D000704:Analysis of Variance; D000818:Animals; D001237:Asphyxia / Q000503:physiopathology; D001921:Brain / Q000187:drug effects / Q000503:physiopathology*; D001923:Brain Chemistry / Q000187:drug effects; D003080:Cold Temperature; D007035:Hypothermia / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism / Q000503:physiopathology*; D008315:Malondialdehyde / Q000378:metabolism; D009460:Neurologic Examination; D009496:Neurotensin / Q000031:analogs & derivatives* / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D015424:Reperfusion / Q000379:methods; D013997:Time Factors
C477786:NT77, rat; D009496:Neurotensin; D008315:Malondialdehyde