Effects of mild hypothermia on metabolic disturbances in fetal hippocampal slices after oxygen/glucose deprivation depend on depth and time delay of cooling.
OBJECTIVE
There is increasing evidence from animal experiments that mild hypothermia induced during or after cerebral ischemia might protect the immature brain from neuronal cell damage. However, the exact interrelation between the postischemic time delay and the degree of mild hypothermia by which to achieve neuroprotective effects on ischemic insults of different severity has not yet been elucidated systematically. To determine optimal neuroprotection, we studied the interaction between these variables in a recently modified hippocampal slice model.


METHODS
We investigated the recovery of energy metabolism and protein synthesis (PSR) in hippocampal slices from mature fetal guinea pigs after 20, 30, or 40 minutes of oxygen and glucose deprivation (OGD). Hypothermia of varying degrees was induced immediately or 2 or 4 hours after OGD and lasted for 12 hours. Prolonged inhibition of PSR after ischemia has been shown to be a sensitive marker of neuronal cell damage.


RESULTS
Hypothermia initiated immediately after OGD significantly improved the recovery of energy metabolism and PSR. If there was a 2-hour delay in the onset of hypothermia, neuroprotection depended on the degree of hypothermia. Reduction of the incubation temperature to 31C diminished the disturbances of energy metabolism and PSR, whereas lowering the bath temperature to only 34C was not effective. Hypothermia induced 4 hours after OGD did not have any influence on the recovery of energy metabolism and PSR.


CONCLUSIONS
We conclude that the effects of mild hypothermia on metabolic disturbances in hippocampal slices of mature fetal guinea pigs depended on the intervention delay and the degree of cooling. The shorter the postischemic intervention delay and the greater the degree of hypothermia, the better the neuroprotective effect seems to be.
Garnier
Y
Y
Department of Obstetrics and Gynecology, Ruhr-Universität Bochum, D-44892 Bochum, Germany.
Pfeiffer
D
D
Jensen
A
A
Berger
R
R
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003080:Cold Temperature; D004734:Energy Metabolism; D005947:Glucose / Q000008:administration & dosage*; D006168:Guinea Pigs; D006624:Hippocampus / Q000196:embryology* / Q000378:metabolism*; D066298:In Vitro Techniques; D010100:Oxygen / Q000008:administration & dosage*; D014176:Protein Biosynthesis; D013997:Time Factors
D000255:Adenosine Triphosphate; D005947:Glucose; D010100:Oxygen