Postischemic Nitrous Oxide Alone Versus Intraischemic Nitrous Oxide in the Presence of Isoflurane: What It May Change for Neuroprotection Against Cerebral Stroke in the Rat

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To the Editor: Warner et al. (1) found no neuroprotective effect of intraischemic nitrous oxide in rats anesthetized with isoflurane. We would like to draw the authors’ attention regarding our finding of a neuroprotective action of postischemic subanesthetic nitrous oxide (0.6 minimum anesthetic concentration) in freely moving, thereby physiologically self-regulated, awake rats compared with control animals treated with postischemic medical air in similar environmentally controlled conditions (2). Differences in neuroprotection between postischemic nitrous oxide alone (2,3) and intraischemic nitrous oxide-isoflurane (1) and convergences in neuroprotection between postischemic xenon alone and intraischemic xenon-isoflurane (2–4) are likely attributable to the respective interactions of nitrous oxide and xenon with isoflurane. Indeed, neither nitrous oxide nor xenon alone induced apoptosis; however, when given with isoflurane in neonatal rats, nitrous oxide enhanced, whereas xenon inhibited, isoflurane-induced apoptosis (5). Whether such an adverse interaction between nitrous oxide and isoflurane occurs in young adult rats subjected to transient cerebral ischemia, this may counteract the neuroprotective antagonistic action of nitrous oxide at the N-methyl-d-aspartate receptor (6). Finally, further support for a neuroprotective action of postischemic nitrous oxide alone on histologic outcome is that post-treatment with nitrous oxide (or xenon) reduces neuronal death induced by intracerebral injection of N-methyl-d-aspartate in awake rats (7). Jacques H. Abraini, PhD, DSc Hélène N. David, PhD Eric T. MacKenzie, PhD Marc Lemaire, MD Université de Caen, France Air Liquide Research Center Jouy-en-Josas, France [email protected]