title: Cooling combined with immediate or delayed xenon inhalation provides equivalent long-term neuroprotection after neonatal hypoxia-ischemia.
abstract: Hypothermia (HT) improves outcome after neonatal hypoxia-ischemia. Combination therapy may extend neuroprotection. The noble anesthetic gas xenon (Xe) has an excellent safety profile. We have shown earlier that 3 h of 50% Xe plus HT (32 degrees C) additively gives more protection (72%) than either alone (HT=31.1%, Xe=10.2%). Factors limiting clinical use include high-cost and specialist administration requirements. Thus, combinations of 1 h of 50% Xe were administered concurrently for either the first (1 h(Immediate)Xe) or last (1 h(Delayed)Xe) of 3 h of posthypoxic-ischemic HT as compared with 3 h of 50%Xe/HT to investigate how brief Xe exposure with a delay would affect efficacy. An established neonatal rat hypoxia-ischemia model was used. Serial functional neurologic testing into adulthood was performed, followed by neuropathological examination. Xenon with HT was more effective with longer Xe duration (3 h versus 1 h) (P=0.015). However, 1 h Xe/3 h HT resulted in better neuroprotection than 3 h HT alone (P=0.03), this significant effect was also present with 1 h Xe after a 2-h delay. One (immediate or with a delay) or 3 h Xe also significantly improved motor function (P=0.024). Females had significantly better motor scores than males, but no sex-dependent difference in pathology results. The neuroprotection of short, delayed Xe treatment would allow transport to specialist facilities to receive Xe.
authors.affiliation: Department of Clinical Sciences at South Bristol, University of Bristol, Bristol, UK.
authors.forename: Marianne
authors.initials: M
authors.lastname: Thoresen
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Hobbs
authors.forename: Tommy
authors.initials: T
authors.lastname: Wood
authors.forename: Ela
authors.initials: E
authors.lastname: Chakkarapani
authors.forename: John
authors.initials: J
authors.lastname: Dingley
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000831:Animals, Newborn; D003080:Cold Temperature; D004195:Disease Models, Animal; D005260:Female; D020925:Hypoxia-Ischemia, Brain / Q000628:therapy*; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use; D051381:Rats; D012737:Sex Factors; D013997:Time Factors; D014978:Xenon / Q000008:administration & dosage*
chemical_list: D018696:Neuroprotective Agents; D014978:Xenon