New experimental and clinical data on the efficacy of pharmacological magnesium infusions in cerebral infarcts.
Multiple metabolic processes have been identified within the critically perfused ischaemic penumbra on the margins of cerebral infarcts. Intervention in many of these processes has been neuroprotective, notably blockade of glutamate receptors such as the N-methyl D-aspartate (NMDA) receptor. Magnesium may act as a neuroprotective agent through vascular effects (increasing regional cerebral blood flow to ischaemic tissue, anticonstrictor effects against vascular mediators, vasodilatation of the cerebral circulation) or neuronal effects. Neuronal effects include block of the NMDA receptor ion channel, calcium antagonism at voltage-gated channels, enhanced buffering of intracellular calcium ions, and enhanced regeneration of adenosine triphosphate. Magnesium infusions of sulphate or chloride salts are significantly neuroprotective in standard animal focal cerebral ischaemia models, with benefits being evident at serum concentrations attainable in humans. Mg systemic infusion causes rises in cerebrospinal fluid and brain magnesium concentrations. Magnesium is also neuroprotective in other models of cerebral ischaemia. Three clinical trials in acute stroke have involved just over 100 patients. No adverse effects have been observed, and trends favouring magnesium treatment have been seen. A large multicentre clinical trial testing the efficacy of magnesium sulphate is underway, and should report within 4 years.
Muir
K W
KW
Department of Neurology, Southern General Hospital, Glasgow, Scotland. k.muir@clinmed.gla.ac.uk
D002545:Brain Ischemia / Q000503:physiopathology; D002544:Cerebral Infarction / Q000188:drug therapy / Q000503:physiopathology*; D002561:Cerebrovascular Disorders / Q000188:drug therapy; D004195:Disease Models, Animal; D006801:Humans; D008274:Magnesium / Q000494:pharmacology / Q000627:therapeutic use*; D015337:Multicenter Studies as Topic; D018696:Neuroprotective Agents / Q000627:therapeutic use; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D008274:Magnesium