Bioenergetic recovery following ischemia in brain slices studied by 31P-NMR spectroscopy: differential age effect of depolarization mediated by endogenous nitric oxide.
Proximate neurotoxic mechanisms during postischemic recovery may be influenced by stage of development and complicating factors such as cortical spreading depression or secondary brain insult. Using 31P nuclear magnetic resonance spectroscopy, we have monitored pH and cellular energy metabolites phosphocreatine (PCr) and ATP in the ex vivo rat cerebral cortex before, during, and after substrate and oxygen deprivation, which represents "in vitro ischemia." There were important developmental differences in resistance and response to an ischemic insult. Twenty-one-day-old (P21) rat cortical slices had no detectable beta-ATP or PCr at the end of a 20-min insult, while 7-day-old (P7) slices had 50 +/- 13.7% (mean +/- SD, n = 12) and 17 +/- 14.8% relative to preischemia levels, respectively. Postischemic depolarization resulted in age-dependent effects on PCr (p < 0.05): In the older tissue, depolarization significantly worsened the recovery of PCr, whereas in young tissue it ameliorated recovery. This amelioration could be prevented by inhibiting nitric oxide production with methylene blue (depolarization-methylene blue interaction, p < 0.05) and enhanced by administration of the nitric oxide donor glyceryl trinitrate (GTN; p < 0.01). However, in P21 tissue, GTN further exacerbated injury (age-GTN interaction, p < 0.01). Therefore, in this vascular-independent preparation, a neuronal or glial nitric oxide-dependent mechanism appears to confer improved postischemic bioenergetic recovery in the developing brain compared with the mature brain.
Paediatric Intensive Care Unit, Great Ormond Street Hospital for Children, London, England.
R C
RC
Tasker
S K
SK
Sahota
S R
SR
Williams
D000255:Adenosine Triphosphate / Q000378:metabolism; D000375:Aging / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004734:Energy Metabolism / Q000502:physiology*; D066298:In Vitro Techniques; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D009569:Nitric Oxide / Q000502:physiology*; D005996:Nitroglycerin / Q000494:pharmacology; D010725:Phosphocreatine / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D051381:Rats; D013654:Taurine / Q000032:analysis
D010725:Phosphocreatine; D013654:Taurine; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D005996:Nitroglycerin; D011188:Potassium