Differential effects of hypothermia on early and late epileptiform events after severe hypoxia in preterm fetal sheep.
Moderate cerebral hypothermia is consistently neuroprotective after experimental hypoxia-ischemia; however, its mechanisms remain poorly defined. Using a model of complete umbilical cord occlusion for 25 min in 0.7 gestation fetal sheep, we examined the effects of cerebral hypothermia (fetal extradural temperature reduced from 39.5 +/- 0.2 degrees C to <34 degrees C; mean +/- SD), from 90 min to 70 h after the end of the insult, on postocclusion epileptiform activity. In the first 6 h after the end of occlusion, fetal electroencephalographic (EEG) activity was abnormal with a mixture of fast and slow epileptiform transients superimposed on a suppressed background; seizures started a mean of 8 h after occlusion. There was a close correlation between numbers of these EEG transients and subsequent neuronal loss in the striatum after 3 days recovery (r(2) = 0.65, P = 0.008). Hypothermia was associated with a marked reduction in numbers of epileptiform transients in the first 6 h, reduced amplitude of seizures, and reduced striatal neuronal loss. In conclusion, neuroprotection with delayed, prolonged head cooling after a severe asphyxial insult in the preterm fetus was associated with potent, specific suppression of epileptiform transients in the early recovery phase but not of numbers of delayed seizures.
Bennet
L
L
Department of Physiology, Faculty of Medicine and Health Science, The University of Auckland, Private Bag 92019, Auckland, New Zealand.
Dean
J M
JM
Wassink
G
G
Gunn
A J
AJ
D000818:Animals; D001831:Body Temperature / Q000502:physiology*; D001921:Brain / Q000098:blood supply / Q000503:physiopathology; D020520:Brain Infarction / Q000209:etiology / Q000503:physiopathology / Q000628:therapy; D002560:Cerebrovascular Circulation / Q000502:physiology; D003342:Corpus Striatum / Q000098:blood supply / Q000503:physiopathology; D019610:Cytoprotection / Q000502:physiology; D004195:Disease Models, Animal; D004569:Electroencephalography; D004827:Epilepsy / Q000209:etiology* / Q000503:physiopathology / Q000628:therapy*; D005260:Female; D005311:Fetal Hypoxia / Q000503:physiopathology*; D005333:Fetus / Q000503:physiopathology; D007036:Hypothermia, Induced; D002534:Hypoxia, Brain / Q000209:etiology / Q000503:physiopathology / Q000628:therapy; D020925:Hypoxia-Ischemia, Brain / Q000150:complications* / Q000503:physiopathology; D009410:Nerve Degeneration / Q000209:etiology / Q000503:physiopathology / Q000628:therapy; D011247:Pregnancy; D012756:Sheep; D013997:Time Factors; D016896:Treatment Outcome