title: Magnesium neuroprotection is limited in humans with acute brain injury.
abstract: 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.
authors.affiliation: Department of Anesthesiology, Duke University School of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: J Andrew
authors.initials: JA
authors.lastname: McKee
authors.forename: Randall P
authors.initials: RP
authors.lastname: Brewer
authors.forename: Gary E
authors.initials: GE
authors.lastname: Macy
authors.forename: Cecil O
authors.initials: CO
authors.lastname: Borel
authors.forename: James D
authors.initials: JD
authors.lastname: Reynolds
authors.forename: David S
authors.initials: DS
authors.lastname: Warner
mesh_terms: D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism*; D002545:Brain Ischemia / Q000188:drug therapy; D004461:Eclampsia / Q000517:prevention & control; D005260:Female; D006706:Homeostasis; D006801:Humans; D008274:Magnesium / Q000502:physiology*; D008278:Magnesium Sulfate / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011247:Pregnancy; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy
chemical_list: D018696:Neuroprotective Agents; D008278:Magnesium Sulfate; D008274:Magnesium