Journal
NEUROCRITICAL CARE
Volume 29, Issue 1, Pages 119-127Publisher
HUMANA PRESS INC
DOI: 10.1007/s12028-017-0479-3
Keywords
Glibenclamide; Cardiac arrest; Cerebral edema; Hypothermia
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Funding
- JSPS [17K11564]
- Grants-in-Aid for Scientific Research [17K11564] Funding Source: KAKEN
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Cerebral edema is one of the major causes of mortality following cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). A subunit of the sulfonylurea receptor 1-transient receptor potential M4 (Sur1-TRPM4) channel has been implicated in the pathogenesis of ischemia-evoked cerebral edema. In this study, we examined whether glibenclamide (GBC), a Sur1-TRPM4 channel inhibitor, attenuates cerebral edema following CA/CPR and further examined the efficacy of GBC combined with therapeutic hypothermia. Isoflurane-anesthetized adult male wild-type C57Bl/6 mice subjected to 7-min CA/CPR were randomized into five groups: sham operation, control with normothermia, GBC with normothermia, control with hypothermia, and GBC with hypothermia. The primary outcome was to evaluate regional brain water content; the secondary outcome was to measure blood glucose level, Sur1-TRPM4 expression, and pro-inflammatory factor expression. Compared with normothermia, GBC treatment or hypothermia significantly attenuated brain water content in mice subjected to CA/CPR. GBC combined with hypothermia had no additional effects on attenuating cerebral edema. Pro-inflammatory factor messenger RNA expression (TNF-alpha and IL-6), NF kappa beta activation, and SUR1-TRPM4 levels were upregulated after CA/CPR. Compared with normothermia, hypothermia, but not GBC, partly suppressed these factors' expression. GBC attenuated cerebral edema following CA/CPR by blocking Sur1-TRPM4 channels upregulated by CA insult. The effect of GBC was comparable with that of therapeutic hypothermia alone. These results suggest that GBC is an alternative approach for treating CA-evoked cerebral edema.
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