We have previously reported that prolonged cerebral cooling started 90 min after severe hypoxiaischemia dramatically improves neural outcome(1). Clinically, it may not be feasible to determine prognosis so soon after resuscitation in infants. The aim of this study was to determine whether head cooling delayed until shortly prior to the onset of secondary seizure activity is protective. Unanesthetised near term fetal sheep were subject to 30 min of cerebral ischemia induced by bilateral carotid occlusion. After 5.5 h recovery they were randomized to either cooling (n=7) or sham cooling (n=10) for 72 h. Intrauterine cooling was induced by circulating cold water through a coil around the fetal head. The water temperature was titrated to reduce fetal extradural temperature from 39°C to between 31 and 33°C, while maintaining esophageal temperature above 37°C. Cooling did not lead to fetal hypotension. Cerebral cooling did not prevent the onset of secondary seizures, 6 to 10 h after ischemia, but markedly delayed and attenuated secondary cortical cytotoxic edema(p<0.001). After 5 days recovery there was greater residual parietal EEG activity and reduced (p<0.005) neuronal loss in all regions assessed (e.g. 91±17% vs 46±33% in the parasagittal cortex). Compared with our previous study of cooling starting 90 min after reperfusion, these data suggest that the 5.5 h delay in initiating cooling attentuated neuroprotection somewhat. Delayed selective head cooling begun prior to the secondary phase of injury and continued throughout, is non-invasive and safe, and shows potential to substantially improve the outcome of moderate to severe hypoxic-ischemic encephalopathy.

Log in or create a free account to read this content

Gain free access to this article, as well as selected content from this journal and more on nature.com

Access through your institution

or

Sign in or create an account
Continue with Google
Continue with ORCiD