Effects of mild hypothermia on metabolic disturbances in fetal hippocampalslices after oxygen/glucose deprivation depend on depth and time delay of cooling

OBJECTIVE: There is increasing evidence from animal experiments that mild h ypothermia induced during or after cerebral ischemia ia might protect the i mmatnre brain from neuronal cell damage. However, the exact interrelation b etween the postischemic nine delay and the degree of mild hypothermia by wh ich to achieve neuroprotective effects on ischemic insults of different sev erity has not yet been elucidated systemmatically. To determine optimal neu roprotection, ive studied the interaction between these variables in a rece ntly modified hippocampal slice model. METHODS: We investigated the recovery of energy metabolism and protein synt hesis (PSR) in hippocampal slices from mature fetal guinea pi qs after 20, 30, or 40 minutes of oxygen and glucose deprivation (OGD). Hypothermia of v arying degrees was induced immediately or 2 or 4 hours after OGD and lasted for 12 hours. Prolonged inhibition of PSR ater ischemia has been shown to be it 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 hypothe rmia. Reduction of the incubation temperature to 31C diminished the disturb ances of energy metabolism and PSR, whereas lowering the bath temperature t o only 34C was not effective. Hypothermia induced 4 hours after OGD did not have any influence on the recovery of energy metabolism and PSR. CONCLUSION: We conclude that the effects of mild hypothermia on metabolic d isturbances in hippocampal slices of mature fetal guinea pigs depended on t he intervention delay and the degree of cooling. The shorter the postischem ic intervention delay and the greater the degree of hypothermia, the better the neuroprotective effect seems to be. (J Soc Gynecol Investig 2001;8:198 -205) Copyright (C) 2001 by the Society for Gynecologic Investigation.