Desflurane, isoflurane, and sevoflurane provide limited neuroprotection against neonatal hypoxia-ischemia in a delayed preconditioning paradigm.
BACKGROUND
The volatile anesthetics desflurane, isoflurane, and sevoflurane have been found to produce neuroprotection in various paradigms. The authors used these agents in a delayed preconditioning model to test the hypothesis that they could provide neuroprotection against neonatal hypoxia-ischemia as assessed by a battery of behavioral tests.


METHODS
Institutional Animal Care and Use Committee approval was obtained. A total of 140, C57-129T2 F1 hybrid 9-day-old mice were randomized to 3 h of preconditioning with room air (Group Sham and Group HI), 8.4% desflurane in 40% oxygen (Group D), 1.8% isoflurane (Group I), or 3.1% sevoflurane (Group S). Twenty-four hours later, the Group HI, D, I, and S mice had 60 min of hypoxia-ischemia, and Group Sham had 60 min of sham HI. Surviving animals had behavioral testing, including open field activity, acoustic startle, prepulse inhibition, rotorod, novel object recognition, water mazes, and apomorphine challenge. Histologic analysis was also performed.


RESULTS
Mice in Groups D, I, and S performed better than Group HI and similarly to Group Sham on novel object recognition and apomorphine challenge and better than Group HI but not as well as Group Sham on cued maze testing. All mice exposed to hypoxia-ischemia performed worse than Group Sham on the spatially oriented water mazes with no difference among groups. Histologic sections did not show any significant effect of preconditioning on injury scores.


CONCLUSIONS
Volatile agent preconditioning partially protects perirhinal cortex and striatal dependent functions against moderate to severe neonatal hypoxia-ischemia.
McAuliffe
John J
JJ
Department of Anesthesia, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229-3036, USA. john.mcauliffe@cchmc.org
Loepke
Andreas W
AW
Miles
Lili
L
Joseph
Bernadin
B
Hughes
Elizabeth
E
Vorhees
Charles V
CV
D018685:Anesthetics, Inhalation / Q000627:therapeutic use*; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001058:Apomorphine; D001522:Behavior, Animal / Q000187:drug effects; D001784:Blood Gas Analysis; D001921:Brain / Q000473:pathology; D003463:Cues; D000077335:Desflurane; D004298:Dopamine / Q000502:physiology; D018491:Dopamine Agonists; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology / Q000517:prevention & control*; D007530:Isoflurane / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018782:Maze Learning / Q000187:drug effects; D008738:Methyl Ethers / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D004856:Postural Balance / Q000187:drug effects; D021641:Recognition, Psychology / Q000187:drug effects; D013216:Reflex, Startle / Q000187:drug effects; D000077149:Sevoflurane; D016896:Treatment Outcome; D015430:Weight Gain / Q000187:drug effects
D018685:Anesthetics, Inhalation; D018491:Dopamine Agonists; D008738:Methyl Ethers; D018696:Neuroprotective Agents; D000077149:Sevoflurane; D000077335:Desflurane; D007530:Isoflurane; D001058:Apomorphine; D004298:Dopamine