Cerebral hypothermia is not neuroprotective when started after post-ischemic seizures in fetal sheep

ABSTRACT 2019 _Neuroprotective Strategies for Hypoxic-Ischemic Encephalopathy Platform, Sunday, 5/2_ BACKGROUND. Prolonged cerebral hypothermia is neuroprotective if started within a few

hours of hypoxia-ischemia. However, delayed seizure activity is one of the major clinical indicators of an adverse prognosis after perinatal asphyxia. The aim of this study was to determine

whether head cooling delayed until after the onset of post asphyxial seizures may still be neuroprotective. METHODS. Unanesthetized near term fetal sheep in utero received 30 min of cerebral

ischemia induced by bilateral carotid artery occlusion. 8.5 h later they received either cooling (n=5) or sham cooling (n=13) until 72 h after the insult. Intrauterine cooling, induced by

circulating cold water through a coil around the fetal head, was titrated to reduce fetal extradural temperature from 39.4 ± 0.1°C to between 30 and 33°C. RESULTS. Cerebral ischemia led to

the delayed development of intense epileptiform activity, from 6 to 8 h post-insult, followed by a marked secondary rise in cortical impedance (a measure of cytotoxic edema), and in carotid

blood flow. Cerebral cooling markedly attenuated the secondary rise in impedance and reduced carotid blood flow (p<0.001). There was a significant transient fall in cerebral oxygen

extraction in the sham cooled but not the cooled group at 24 h; this time point corresponded with the peak of the phase of secondary hypertension. After 5 days recovery there was no

significant difference in the loss of parietal EEG activity relative to baseline, in the hypothermia compared with the control group (-12.5 ± 1.4 vs -15.2 ± 1.2 dB, mean ± S.E.M., N.S.).

Overall neuronal loss was not significantly lower in the hypothermia group compared with the sham cooled group (p=0.11, repeated measures ANOVA). In particular, there was no significant

difference in neuronal loss in the parasagittal cortex (82 ± 9 vs 90 ± 5 %, N.S.) or the hippocampus. CONCLUSIONS. Delayed, prolonged head cooling begun after the onset of post-ischemic

seizures was not associated with overall neuroprotection. These data highlight the importance of intervention in the latent phase after reperfusion, but before the onset of secondary injury

as shown by seizures and other pathological events. There is a need for further studies of the processes in this phase which precedes irreversible programmed cell death. AUTHOR INFORMATION

AUTHORS AND AFFILIATIONS * Research Centre for Developmental Medicine and Biology, Auckland University, Auckland, NZL Tania R Gunn, Laura Bennet, Mark I Gunning, Peter D Gluckman & 

Alistair J Gunn Authors * Tania R Gunn View author publications You can also search for this author inPubMed Google Scholar * Laura Bennet View author publications You can also search for

this author inPubMed Google Scholar * Mark I Gunning View author publications You can also search for this author inPubMed Google Scholar * Peter D Gluckman View author publications You can

also search for this author inPubMed Google Scholar * Alistair J Gunn View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and

permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Gunn, T., Bennet, L., Gunning, M. _et al._ Cerebral Hypothermia Is Not Neuroprotective When Started after Post-Ischemic Seizures in Fetal

Sheep. _Pediatr Res_ 45, 342 (1999). https://doi.org/10.1203/00006450-199904020-02035 Download citation * Issue Date: 01 April 1999 * DOI: https://doi.org/10.1203/00006450-199904020-02035

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