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

Mimily Harsono, Massroor Pourcyrous, Elliott J. Jolly, Amy Curry, Alexander L. Fedinec, Jianxiong Liu, Shyamali Basuroy, Daming Zhuang, Charles Leffler, Elena Parfenova

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)H1202-H1213
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume311
Issue number5
DOIs
StatePublished - Jan 1 2016

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Blood Vessels
Seizures
Head
Cerebrovascular Circulation
Bicuculline
Stroke
Vasodilator Agents
Wounds and Injuries
Brain
DNA Nucleotidylexotransferase
Vascular System Injuries
Ice
Arterioles
Anticonvulsants
Endothelium
Electroencephalography
Epilepsy
Swine
Endothelial Cells
Staining and Labeling

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Selective head cooling during neonatal seizures prevents postictal cerebral vascular dysfunction without reducing epileptiform activity. / Harsono, Mimily; Pourcyrous, Massroor; Jolly, Elliott J.; Curry, Amy; Fedinec, Alexander L.; Liu, Jianxiong; Basuroy, Shyamali; Zhuang, Daming; Leffler, Charles; Parfenova, Elena.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 311, No. 5, 01.01.2016, p. H1202-H1213.

Research output: Contribution to journalArticle

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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.",
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