Alcohol Intoxication May Exacerbate the Effects of Blunt Cranial Trauma Through Changes in Brain Free Magnesium Levels
Robert Vink Ph.D.
Adelaide Centre for Neuroscience Research, School of Medical Sciences, The University of Adelaide, Frome Road, Adelaide, SA 5005, Australia.
Search for more papers by this authorRoger W. Byard M.D.
Adelaide Centre for Neuroscience Research, School of Medical Sciences, The University of Adelaide, Frome Road, Adelaide, SA 5005, Australia.
Search for more papers by this authorRobert Vink Ph.D.
Adelaide Centre for Neuroscience Research, School of Medical Sciences, The University of Adelaide, Frome Road, Adelaide, SA 5005, Australia.
Search for more papers by this authorRoger W. Byard M.D.
Adelaide Centre for Neuroscience Research, School of Medical Sciences, The University of Adelaide, Frome Road, Adelaide, SA 5005, Australia.
Search for more papers by this authorAbstract
Abstract: Moderate to high levels of alcohol decrease brain intracellular free magnesium concentration, a factor known to be critical in brain injury. Phosphorus magnetic resonance spectroscopy was used to examine changes to brain free magnesium concentration after blunt cranial trauma in alcohol-intoxicated rats. Rats exposed acutely or chronically to alcohol sufficient to increase blood alcohol levels to between 150 and 350 mg/dL demonstrated a brain free magnesium level that was 20–50% less than in nonintoxicated animals (p < 0.01). After injury, brain free magnesium levels declined more rapidly and to a greater extent in alcohol-affected animals than in nonintoxicated control animals (p < 0.001). As both preinjury depletion of magnesium and degree of magnesium decline after brain injury have been associated with poor recovery, these findings suggest that moderate to severe alcohol intoxication may predispose the brain to a worse outcome by reducing brain free magnesium levels, both before and after injury.
References
- 1 Byard RW, Bhatia KD, Reilly PL, Vink R. How rapidly does cerebral swelling follow trauma? Observations using an animal model and possible implications in infancy Leg Med (Tokyo) 2009; 11(Suppl. 1): S128–31.
- 2 Byard RW, Blumbergs P, Rutty G, Sperhake J, Banner J, Krous HF. Lack of evidence for a causal relationship between hypoxic-ischemic encephalopathy and subdural hemorrhage in fetal life, infancy, and early childhood. Pediatr Dev Pathol 2007; 10: 348–50.
- 3 Byard RW, Vink R. The second impact syndrome. Forensic Sci Med Pathol 2009; 5: 36–8.
- 4 Kelly DF, Lee SM, Pinanong PA, Hovda DA. Paradoxical effects of acute ethanolism in experimental brain injury. J Neurosurg 1997; 86: 876–82.
- 5 Ramsay DA, Shkrum MJ. Homicidal blunt head trauma, diffuse axonal injury, alcohol intoxication, and cardiorespiratory arrest: a case report of a forensic syndrome of acute brainstem dysfunction. Am J Forensic Med Pathol 1995; 16: 107–14.
- 6 Zink BJ, Feustel PJ. Effects of ethanol on respiratory function in traumatic brain injury. J Neurosurg 1995; 82: 822–8.
- 7 Opreana RC, Kuhn D, Basson MD. Influence of alcohol on mortality in traumatic brain injury. J Am Coll Surg 2010; 210: 997–1007.
- 8 Kodikara S. A death due to concussive brain injury augmented by alcohol. Forensic Sci Med Pathol 2007; 3: 283–4.
- 9 Zink BJ, Schultz CH, Wang X, Mertz M, Stern SA, Betz AL. Effects of ethanol on brain lactate in experimental traumatic brain injury with hemorrhagic shock. Brain Res 1999; 837: 1–7.
- 10 Zink BJ, Sheinberg MA, Wang X, Mertz M, Stern SA, Betz AL. Acute ethanol intoxication in a model of traumatic brain injury with hemorrhagic shock: effects on early physiological response. J Neurosurg 1998; 89: 983–90.
- 11 Zink BJ, Walsh RF, Feustel PJ. Effects of ethanol in traumatic brain injury. J Neurotrauma 1993; 10: 275–86.
- 12 Bareyre FM, Saatman KE, Helfaer MA, Sinson G, Weisser JD, Brown AL, et al. Alterations in ionized and total blood magnesium after experimental traumatic brain injury: relationship to neurobehavioral outcome and neuroprotective efficacy of magnesium chloride. J Neurochem 1999; 73: 271–80.
- 13 Vink R, Golding EM, Headrick JP. Bioenergetic analysis of oxidative metabolism following traumatic brain injury in rats. J Neurotrauma 1994; 11: 265–74.
- 14 Vink R, McIntosh TK, Yamakami I, Faden AI. 31P NMR characterization of graded traumatic brain injury in rats. Magn Reson Med 1988; 6: 37–48.
- 15 McIntosh TK, Faden AI, Yamakami I, Vink R. Magnesium deficiency exacerbates and pretreatment improves outcome following traumatic brain injury in rats: 31P magnetic resonance spectroscopy and behavioral studies. J Neurotrauma 1988; 5: 17–31.
- 16 Vink R, Nimmo AJ. Multifunctional drugs for head injury. Neurotherapeutics 2009; 6: 28–42.
- 17 Altura BM, Weaver C, Gebrewold A, Altura BT, Gupta RK. Continuous osmotic minipump infusion of alcohol into brain decreases brain [Mg2+] and brain bioenergetics and enhances susceptibility to hemorrhagic stroke: an in vivo 31P-NMR study. Alcohol 1998; 15: 113–7.
- 18 Mullins PGM, Vink R. Chronic alcohol exposure decreases brain intracellular free magnesium concentration in rats. Neuroreport 1995; 6: 1633–6.
- 19 McIntosh TK, Vink R, Noble L, Yamakami I, Fernyak S, Soares H, et al. Traumatic brain injury in the rat: characterization of a lateral fluid-percussion model. Neuroscience 1989; 28: 233–44.
- 20 Vink R, Mullins PG, Temple MD, Bao W, Faden AI. Small shifts in craniotomy position in the lateral fluid percussion injury model are associated with differential lesion development. J Neurotrauma 2001; 18: 839–47.
- 21 Smolen TN, Smolen A. Blood and brain ethanol concentrations during adsorption and distribution in long-sleep and short-sleep mice. Alcohol 1989; 6: 33–8.
- 22 Lamblin F, Deuceuninck D, De Whitte P. Modulation of alcohol preference by NMDA antagonists in male rats. Alcohol Alcohol 1993; 28: 639–47.
- 23 Vink R, Golding EM, Williams JP, McIntosh TK. Blood glucose concentration does not affect outcome in brain trauma: a 31P MRS study. J Cereb Blood Flow Metab 1997; 17: 50–3.
- 24 Cernak I, Vink R, Natale J, Stoica B, Lea PM 4th, Movsesyan V, et al. The “dark side” of endocannabinoids: a neurotoxic role for anandamide. J Cereb Blood Flow Metab 2004; 24: 564–78.
- 25 Cernak I, Vink R, Zapple DN, Cruz MI, Ahmed F, Chang T, et al. The pathobiology of moderate diffuse traumatic brain injury as identified using a new experimental model of injury in rats. Neurobiol Dis 2004; 17: 29–43.
- 26 Vink R, Cernak I. Regulation of intracellular free magnesium in central nervous system injury. Front Biosci 2000; 5: D656–65.
- 27 Milovanovic AV, DiMaio VJ. Death due to concussion and alcohol. Am J Forensic Med Pathol 1999; 20: 6–9.
- 28 Zink BJ, Schultz CH, Stern SA, Mertz M, Wang X, Johnston P, et al. Effects of ethanol and naltrexone in a model of traumatic brain injury with hemorrhagic shock. Alcohol Clin Exp Res 2001; 25: 916–23.
- 29 Sun H, Zhao H, Sharpe GM, Arrick DM, Mayhan WG. Effect of chronic alcohol consumption on brain damage following transient focal ischemia. Brain Res 2008; 1194: 73–80.
- 30 Genetta T, Lee BH, Sola A. Low doses of ethanol and hypoxia administered together act synergistically to promote the death of cortical neurons. J Neurosci Res 2007; 85: 131–8.
- 31 Vink R, Heath DL, McIntosh TK. Acute and prolonged alterations in brain free magnesium following fluid percussion-induced brain trauma in rats. J Neurochem 1996; 66: 2477–83.
- 32 Heath DL, Vink R. Brain free magnesium concentration is predictive of motor outcome following traumatic axonal brain injury in rats. Magnes Res 1999; 12: 269–77.
- 33 Saatman KE, Bareyre FM, Grady MS, McIntosh TK. Acute cytoskeletal alterations and cell death induced by experimental brain injury are attenuated by magnesium treatment and exacerbated by magnesium deficiency. J Neuropathol Exp Neurol 2001; 60: 183–94.
- 34 Altura BM, Gebrewold A, Zhang AM, Altura BT, Gupta RK. Magnesium deficiency exacerbates brain injury and stroke mortality induced by alcohol—a P-31-NMR in vivo study. Alcohol 1998; 15: 181–3.
- 35 Feldman Z, Gurevitch B, Artru AA, Oppenheim A, Shohami E, Reichenthal E, et al. Effect of magnesium given 1 hour after head trauma on brain edema and neurological outcome. J Neurosurg 1996; 85: 131–7.
- 36 Bareyre FM, Saatman KE, Raghupathi R, McIntosh TK. Postinjury treatment with magnesium chloride attenuates cortical damage after traumatic brain injury in rats. J Neurotrauma 2000; 17: 1029–39.
- 37 Heath DL, Vink R. Improved motor outcome in response to magnesium therapy received up to 24 hours after traumatic diffuse axonal brain injury in rats. J Neurosurg 1999; 90: 504–9.
- 38 Faden AI, Demediuk P, Panter SS, Vink R. The role of excitatory amino acids and NMDA receptors in traumatic brain injury. Science 1989; 244: 798–800.
- 39 Altura BM, Altura BT, Gupta RK. Alcohol intoxication results in rapid loss in free magnesium in brain and disturbances in brain bioenergetics: relation to cerebrospasm, alcohol-induced strokes, and barbiturate anesthesia-induced deaths. Magnes Trace Elem 1992; 10: 122–35.
- 40 Donkin JJ, Vink R. Mechanisms of cerebral edema in traumatic brain injury: therapeutic developments. Curr Opin Neurol 2010; 23: 293–9.
- 41 Collins MA, Zou JY, Neafsey EJ. Brain damage due to episodic alcohol exposure in vivo and in vitro: furosemide neuroprotection implicates edema-based mechanism. FASEB J 1998; 12: 221–30.
- 42 Bara M, Guiet-Bara A. Potassium, magnesium and membranes. Magnesium 1984; 3: 212–25.
- 43 Abdul Muneer PM, Alikunju S, Szlachetka AM, Haorah J. Inhibitory effects of alcohol on glucose transport across the blood-brain barrier leads to neurodegeneration: preventive role of acetyl-L: -carnitine. Psychopharmacology (Berl) 2011; 214: 707–18.