title: Selective head cooling during neonatal seizures prevents postictal cerebral vascular dysfunction without reducing epileptiform activity.
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 head-cooled groups. During the delayed postictal period, endothelium-dependent 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.
authors: Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee; and.
authors: Mimily
authors: M
authors: Harsono
authors: Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee; and.
authors: Massroor
authors: M
authors: Pourcyrous
authors: Department of Biomedical Engineering, University of Memphis, Memphis, Tennessee.
authors: Elliott J
authors: EJ
authors: Jolly
authors: Department of Biomedical Engineering, University of Memphis, Memphis, Tennessee.
authors: Amy
authors: A
authors: de Jongh Curry
authors: Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee; and.
authors: Alexander L
authors: AL
authors: Fedinec
authors: Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee; and.
authors: Jianxiong
authors: J
authors: Liu
authors: Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee; and.
authors: Shyamali
authors: S
authors: Basuroy
authors: Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee; and.
authors: Daming
authors: D
authors: Zhuang
authors: Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee; and.
authors: Charles W
authors: CW
authors: Leffler
authors: Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee; and hparfeno@uthsc.edu.
authors: Helena
authors: H
authors: Parfenova
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001160:Arterioles / Q000503:physiopathology*; D001640:Bicuculline / Q000633:toxicity; D002536:Cerebral Arteries / Q000503:physiopathology*; D002560:Cerebrovascular Circulation; D002561:Cerebrovascular Disorders / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control; D003292:Convulsants / Q000633:toxicity; D004569:Electroencephalography; D042783:Endothelial Cells / Q000166:cytology; D005260:Female; D006257:Head; D007036:Hypothermia, Induced / Q000379:methods*; D020287:In Situ Nick-End Labeling; D008297:Male; D012640:Seizures / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*; D013552:Swine; D014664:Vasodilation / Q000502:physiology*
chemical_list: D003292:Convulsants; D001640:Bicuculline
keywords: cerebral circulation; cerebral vascular injury; epilepsy; mild hypothermia; newborn pigs