Magnesium neuroprotection is limited in humans with acute brain injury

• Published in: Neurocritical care 2005-01, Vol.2 (3), p.342-351
• Main Authors: McKee, J Andrew, Brewer, Randall P, Macy, Gary E, Borel, Cecil O, Reynolds, James D, Warner, David S
• Format: Article
• Language: English
• Subjects: Brain Injuries - drug therapy; Brain Injuries - metabolism; Brain Ischemia - drug therapy; Clinical trials; Eclampsia - prevention & control; Female; Homeostasis; Humans; Magnesium - physiology; Magnesium Sulfate - pharmacokinetics; Magnesium Sulfate - therapeutic use; Neuroprotective Agents - pharmacokinetics; Neuroprotective Agents - therapeutic use; Pregnancy; Subarachnoid Hemorrhage - drug therapy; Traumatic brain injury
• ISSN: 1541-6933; 1541-6933; 1556-0961
• DOI: 10.1385/NCC:2:3:342

Based on the results of preclinical models, magnesium sulfate (MgSO4) has gained attention as a putative neuroprotective agent. The negative results of a large-scale, randomized clinical trial using MgSO4 in acute stroke have tempered the initial enthusiasm for a neuroprotective benefit of the ion. Additional, large-scale clinical trials in stroke and other forms of brain injury are underway. This article reviews the central nervous system (CNS) physiology of Mg++, disordered Mg++ homeostasis in acute brain injury, preclinical and preliminary clinical foundations of current clinical trials, and the data regarding the CNS bio-availability of MgSO4 an important requisite for neuroprotective therapy. Although human studies have confirmed that moderate hypermagnesemia is well-tolerated and feasible, only modest elevation of cerebrospinal fluid (CSF) [Mg++] occurs. This modest increment of CSF [Mg++] in brain-injured humans occurs in the range of 10 to 19%. However, experimental evidence has yet to establish whether this modest elevation is sufficient for neuroprotection. Because of the limited CNS passage of the ion, further experimental work is needed to define the neuroprotective threshold of [Mg++] in the injured brain.