Magnesium protects against cocaine-induced hemorrhagic stroke in a rat model: a 31P-NMR in-vivo study.
In-vivo 31P-nuclear magnetic resonance (NMR) studies were undertaken with anesthetized rats to determine: a. whether systemic administration of MgCl2 could protect animals against cocaine-induced hemorrhagic stroke, and b. whether a relationship exists between basal levels of brain intracellular free magnesium ions ([Mg2+]i), phosphometabolites, and stroke risk. Repeat 31P-NMR spectra were obtained at various intervals of time (3-120 min, or up until death) after administration of cocaine (5 + 30 mg/kg). Ion selective electrodes were used to measure plasma Mg2+, K+, Na+ and Ca2+. Forty percent of animals died in the absence of Mg2+ infusion following high dosage of cocaine. Only 13% died with cocaine following Mg2+ infusion (p <0.005). In the Mg2+-protected animals, neither brain [Mg2+]i,intracellular pH (pHi), [phosphocreatine-PCr]/[ATP], nor brain [inorganic phosphate-Pi]/[ATP] fell when toxic and lethal doses of cocaine were given. Low basal brain [Mg2+]i (275 +/- 24 vs. 466 +/- 35 microM, p <0.01) and low basal brain [PCr] (3.36 +/- 0.35 vs. 4.26 +/- 0.24 mM, p <0.01) were found to be associated with a 3-fold increased incidence of stroke. A positive correlation (r = 0.31, p <0.03) between brain [Mg2+]1 and [PCr]/[ATP] was found. It is possible that both brain [Mg2+]i and [PCr] may be useful as important predictors of susceptibility to cocaine-induced hemorrhagic stroke.
Altura
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BM
Department of Physiology, State University of New York, Health Science Center at Brooklyn, 450 Clarkson Avenue, Brooklyn, New York 11203, USA.
Gebrewold
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A
Altura
B T
BT
Gupta
A R
AR
D000818:Animals; D002543:Cerebral Hemorrhage / Q000139:chemically induced / Q000517:prevention & control*; D003042:Cocaine / Q000633:toxicity*; D018765:Dopamine Uptake Inhibitors / Q000633:toxicity*; D008274:Magnesium / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010759:Phosphorus Isotopes; D051381:Rats; D017208:Rats, Wistar; D020521:Stroke / Q000139:chemically induced / Q000517:prevention & control*
D018765:Dopamine Uptake Inhibitors; D010759:Phosphorus Isotopes; D008274:Magnesium; D003042:Cocaine