Role of brain [Mg2+]i in alcohol-induced hemorrhagic stroke in a rat model: a 31P-NMR in vivo study.
One hundred percent of anesthetized rats administered 6.6 gm/kg of ethanol IP died within 10-35 min of alcohol injection; upon autopsy of the brain all demonstrated profound subarachnoid and intracranial bleeding, clear signs of hemorrhagic stroke. Pretreatment of rats with 4 mumol/min MgCl2, but not saline, via IV administration (for 30-45 min), prevented hemorrhagic stroke in all animals so treated with 6.6 gm/kg ethanol. Administration of the stroke dose of alcohol resulted in rapid (within 3-5 min) and marked deficits in whole brain intracellular free Mg ([Mg2++]i) as observed by in vivo 31P-NMR spectroscopy. Intracellular pH (pHi) and the phosphocreatine [PCr]/[ATP] ratio also fell following a significant fall in brain [Mg2+]i). Brains of rats that exhibited strokelike events, upon death and autopsy, demonstrated continued and marked intracellular acidosis with progressive fall in the [PCr]/[ATP] ratio and elevation of inorganic phosphate (Pi) and [H+]i; these events were not accompanied by any rises in systemic arterial blood pressure. Rats pretreated with MgCl2 exhibited relatively stable brain [Mg2+]i, and essentially unchanged pHi, [PCr], [ATP], or [Pi] following alcohol administration, although such animals exhibited threefold alterations in plasma Mg2+, as measured by ion selective electrodes. These observations suggest that high alcohol ingestion can result in severe vasospasm, ischemia, and rupture of blood vessels probably as a consequence of depletion of brain [Mg2+]i, events that can be prevented by Mg2+ pretreatment.
Altura
B M
BM
Department of Physiology, State University of New York, Health Science Center at Brooklyn 11203, USA.
Gebrewold
A
A
Altura
B T
BT
Gupta
R K
RK
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002543:Cerebral Hemorrhage / Q000139:chemically induced* / Q000378:metabolism; D002561:Cerebrovascular Disorders / Q000139:chemically induced* / Q000378:metabolism; D000431:Ethanol; D007425:Intracellular Membranes / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009994:Osmolar Concentration; D010758:Phosphorus; D051381:Rats; D017208:Rats, Wistar
D010758:Phosphorus; D000431:Ethanol; D008274:Magnesium