Although there is general agreement that chronic ingestion of alcohol poses great risks for normal cardiovascular functions and peripheral-vascular homeostasis, a direct cause and effect between the real phenomena of alcohol-induced headache and risk of brain injury and stroke is not appreciated. “Binge drinking” of alcohol is associated with an ever-growing number of strokes and sudden death. It is becoming clear that alcohol ingestion can result in profoundly different actions on the cerebral circulation (e.g., vasodilation, vasoconstriction-spasm, vessel rupture), depending upon dose and physiologic state of host. Using rats, it has been demonstrated that acute, high doses of ethanol can result in stroke-like events concomitant with alterations in brain bioenergetics. We review recent in vivo findings obtained with 31P-NMR spectroscopy, optical reflectance spectroscopy, and direct in vivo microcirculatory studies on the intact brain. Alcohol-induced hemorrhagic stroke is preceded by a rapid fall in brain intracellular free magnesium ions ([Mg 2+] i) followed by cerebrovasospasm and reductions in phosphocreatine (PCr)/ATP ratio, intracellular pH, and the cytosolic phosphorylation potential (CPP) with concomitant rises in deoxyhemoglobin (DH), mitochondrial reduced cytochrome oxidase aa 3 (rCOaa 3), blood volume, and intracellular inorganic phosphate (Pi). Using osmotic mini-pumps implanted in the third cerebral ventricle, containing 30% ethanol, it was found that brain [Mg 2+] i is reduced 30% after 14 days; brain PCr fell 15%, whereas the CPP fell 40%. Such animals became susceptible to stroke from nonlethal doses of ethanol. Human subjects with mild head injury have been found to exhibit early deficits in serum ionized Mg (IMg 2+); the greater the degree of early head injury (30 min–8 h), the greater and more profound the deficit in serum IMg 2+ and the greater the ionized Ca (ICa 2+) to IMg 2+ ratio. Patients with histories of alcohol abuse or ingestion of alcohol prior to head injury exhibited greater deficits in IMg 2+ (and higher ICa 2+/IMg 2+ ratios) and, unlike the subjects without alcohol, did not leave the hospital for at least several days. Women, for some unknown reason, exhibit a much higher incidence of morbidity and mortality from subarachnoid hemorrhage (SAH) than men. Data on 105 men and women with different types of stroke indicate that, on the average, a 20% deficit in serum IMg 2+ is seen; total Mg (TMg) or blood pH is usually near normal. Women with SAH, however, exhibit much lower IMg 2+ and higher ICa 2+/IMg 2+ ratios; the presence of ethanol in the blood is associated with even more depression in IMg 2+ in SAH in women. It is possible that prior alcohol ingestion is, in large measure, responsible for a great deal of this unexplained higher incidence of SAH in women. It has recently been reported that the cyclical changes in estrogenic hormones appear to control the serum IMg 2+ level in young women. A surge in estrogenic levels prior to SAH could thus precipitate, in part, the SAH. In other human studies, it has been shown that migraines and headache, dizziness, and hangover, which accompany ethanol ingestion, are associated with rapid deficits in serum IMg 2+ but not in TMg. The former, and the alcohol-associated headache, can be ameliorated with IV administration of MgSO 4. Premenstrual tension-headache (PTH) and its exacerbation by alcohol in women is also accompanied by deficits in IMg 2+, and elevation in serum ICa 2+/IMg 2+; IV MgSO 4 corrects the PTH and the serum deficit in IMg 2+. Animal experiments show that IV Mg 2+ can prevent alcohol-induced hemorrhagic stroke and the subsequent fall in brain [Mg 2+] i, [PCr], pHi, and CPP. Other recent data indicate that alcohol-induced cellular loss of [Mg 2+] i is associated with cellular Ca 2+ overload and generation of oxygen-derived free radicals; chronic pretreatment with vitamin E prevents alcohol-induced vascular injury and pathology in the brain. New findings on isolated single cerebral vascular smooth muscle cells and the intact, in vivo brain microcirculation implicate lipid peroxidation, reactive oxygen species, PKC isozymes, and activation of NF-κB in the signaling pathways. We believe all of the animal and human data are compatible with the idea that rapid alcohol-induced cellular losses of Mg 2+ help to promote an ischemic pro-oxidant, proinflammay environment that would result in generation of free radicals with membrane lipid peroxidative properties, which can effect irreversible, or refractory, brain injury. Sequential measurement of brain [Mg 2+] (and phosphometabolites) with 31P-NMR spectroscopy and measurement of serum IMg 2+ and ICa 2+ with specific ion-selective electrodes should be of great value in the diagnosis and treatment of alcohol-associated brain injury, headache, and stroke.
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Mar 1, 2000
Tomoko Sankai + 9
Open Access