Selective head cooling during neonatal seizures prevents postictal cerebral vascular dysfunction without reducing epileptiform activity

Authors

Mimily Harsono, University of Tennessee Health Science Center
Massroor Pourcyrous, University of Tennessee Health Science Center
Elliott J. Jolly, University of Memphis
Amy de Jongh Curry, University of MemphisFollow
Alexander L. Fedinec, University of Tennessee Health Science CenterFollow
Jianxiong Liu, University of Tennessee Health Science Center
Shyamali Basuroy, University of Tennessee Health Science Center
Daming Zhuang, University of Tennessee Health Science Center
Charles W. Leffler, University of Tennessee Health Science Center
Helena Parfenova, University of Tennessee Health Science Center

Abstract

Epileptic seizures in neonates cause cerebrovascular injury and impairment of cerebral blood flow (CBF) regulation. In the bicuculline model of seizures in newborn pigs, we tested the hypothesis that selective head cooling prevents deleterious effects of seizures on cerebral vascular functions. Preventive or therapeutic ictal head cooling was achieved by placing two head ice packs during the preictal and/or ictal states, respectively, for the ~2-h period of seizures. Head cooling lowered the brain and core temperatures to 25.6 ± 0.3 and 33.5 ± 0.1°C, respectively. Head cooling had no anticonvulsant effects, as it did not affect the bicuculline-evoked electroencephalogram parameters, including amplitude, duration, spectral power, and spike frequency distribution. Acute and long-term cerebral vascular effects of seizures in the normothermic and head-cooled groups were tested during the immediate (2–4 h) and delayed (48 h) postictal periods. Seizure-induced cerebral vascular injury during the immediate postictal period was detected as terminal deoxynucleotidyl transferase- mediated dUTP nick-end labeling-positive staining of cerebral arterioles and a surge of brain-derived circulating endothelial cells in peripheral blood in the normothermic group, but not in the headcooled groups. During the delayed postictal period, endotheliumdependent cerebral vasodilator responses were greatly reduced in the normothermic group, indicating impaired CBF regulation. Preventive or therapeutic ictal head cooling mitigated the endothelial injury and greatly reduced loss of postictal cerebral vasodilator functions. Overall, head cooling during seizures is a clinically relevant approach to protecting the neonatal brain by preventing cerebrovascular injury and the loss of the endothelium-dependent control of CBF without reducing epileptiform activity.

Publication Title

American Journal of Physiology - Heart and Circulatory Physiology

Recommended Citation

Harsono, M., Pourcyrous, M., Jolly, E., de Jongh Curry, A., Fedinec, A., Liu, J., Basuroy, S., Zhuang, D., Leffler, C., & Parfenova, H. (2016). Selective head cooling during neonatal seizures prevents postictal cerebral vascular dysfunction without reducing epileptiform activity. American Journal of Physiology - Heart and Circulatory Physiology, 311 (5), H1202-H1213. https://doi.org/10.1152/ajpheart.00227.2016