Intracellular chelation of calcium prevents cell damage following severe hypoxia in the rat cerebral cortex as studied by NMR spectroscopy ex vivo.
Nuclear magnetic resonance (NMR) spectroscopy was used to quantify metabolic recovery (by 31P NMR) and neuronal damage (by 1H NMR) following aglycaemic hypoxia in superfused cortical brain slices. Slices were incubated either in the absence or presence of a cell-permeant Ca2+ chelator, 1,2-bis-(2-amino-phenoxy)ethane-N,N,N',N'-tetra-acetic acid acetoxy ester (BAPTA-AM) before exposure to hypoxia in the presence or absence of 1.2 mM Ca2+. Hypoxia in the presence of Ca2+ resulted in metabolic damage as well as time-dependent reduction of a neuronal metabolite, N-acetyl aspartate. The recovery was improved only temporarily by BAPTA under these conditions. Hypoxia in the absence of external Ca2+ did not cause any detectable signs of damage in BAPTA-loaded slices. These data show that combined inhibition of influx and intracellular chelation of Ca2+ render the brain cortex tolerable to severe energy failure.
Gröhn
O
O
NMR Research Group, A.I. Virtanen Institute, University of Kuopio, Finland.
Kauppinen
R
R
D000818:Animals; D002021:Buffers; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D015687:Cell Hypoxia / Q000187:drug effects; D002540:Cerebral Cortex / Q000166:cytology*; D002614:Chelating Agents / Q000494:pharmacology*; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D007773:Lactates / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D009924:Organ Culture Techniques; D010100:Oxygen / Q000494:pharmacology; D010710:Phosphates / Q000378:metabolism / Q000494:pharmacology; D010725:Phosphocreatine / Q000378:metabolism; D010759:Phosphorus Isotopes; D017680:Potassium Compounds / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012965:Sodium Chloride / Q000494:pharmacology; D014316:Tritium
D002021:Buffers; D002614:Chelating Agents; D007773:Lactates; D018696:Neuroprotective Agents; D010710:Phosphates; D010759:Phosphorus Isotopes; D017680:Potassium Compounds; D010725:Phosphocreatine; D014316:Tritium; D012965:Sodium Chloride; D004533:Egtazic Acid; C013216:potassium phosphate; D005947:Glucose; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D010100:Oxygen; D002118:Calcium