Cerebral hypothermia is not neuroprotective when started after postischemic seizures in fetal sheep

Prolonged cerebral hypothermia is neuroprotective if started within a few h ours of hypoxia-ischemia, However, delayed seizure activity is one of the m ajor clinical indicators of an adverse prognosis after perinatal asphyxia. The aim of this study was to determine whether head cooling delayed until a fter the onset of postasphyxial seizures may still be neuroprotective. Unan esthetized near-term fetal sheep in utero received 30 min of cerebral ische mia induced by bilateral carotid artery occlusion. Eight and one-half hours later, they received either cooling (n = 5) or sham cooling (n = 13) until 72 h after the insult. Intrauterine cooling, induced by circulating cold w ater through a coil around the fetal head, was titrated to reduce fetal ext radural temperature from 39.4 +/- 0.1 degrees C to between 30 and 33 degree s C, Cerebral ischemia led to the delayed development of intense epileptifo rm activity from 6 to 8 h postinsult, followed by a marked secondary rise i n cortical impedance (a measure of cytotoxic edema) and in carotid blood fl ow. Cerebral cooling markedly attenuated the secondary rise in impedance an d reduced carotid blood flow (p < 0.001). After 5 d recovery, there was no significant difference in loss of parietal EEG activity relative to baselin e in the hypothermia compared with the control group (-12,5 +/- 1.4 ver sus -15.2 +/- 1.2 dB, mean +/-: SEM, NS) or in parasagittal cortical neuronal loss (82 +/- 9 versus 90 +/- 5%, NS). In conclusion, delayed prolonged head cooling begun after the onset of postischemic seizures was not neuroprotec tive. These data highlight the importance of intervention in the latent pha se, after reperfusion but before the onset of secondary injury.