The effect of non-competitive N-methyl-D-aspartate receptor antagonism on cerebral oedema and cerebral infarct size in the aging ischaemic brain.
Although vulnerability to ischemic neuronal injury is enhanced with age, the aging brain may be less amenable to neuroprotection as a result of quantitative and qualitative changes in the NMDA receptor. In addition, the elderly may be less tolerant of adverse effects of neuroprotective drugs and this might ultimately limit therapeutic potential in human stroke. However, antagonism of the excitotoxic effects of glutamate by parenteral administration of the non competitive NMDA antagonist magnesium has been well tolerated and has shown to be neuroprotective in young animal models of stroke and head injury. We therefore evaluated the potential of magnesium chloride to reduce ischemic neuronal injury in aged rodents subjected to permanent occlusion of the middle cerebral artery. Treatment with magnesium chloride induced hypotension and hyperglycaemia in both adult and aged rats and did not reduce ischemic neuronal injury or cerebral edema. However, despite these adverse haemodynamic and biochemical effects, which may augment cerebral infarct size, ischemic damage was not exacerbated in the treated groups, suggesting that magnesium has the potential to salvage penumbral neurons and that inotropic support and maintenance of normoglycaemia may permit realisation of its neuroprotective potential. This may have important implications for future clinical stroke trials.
Davis
M
M
Department of Surgery (Neurosurgery), University of Newcastle upon Tyne, England, U.K.
Perry
R H
RH
Mendelow
A D
AD
D000375:Aging / Q000473:pathology*; D000818:Animals; D001667:Binding, Competitive; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001929:Brain Edema / Q000188:drug therapy*; D002545:Brain Ischemia / Q000188:drug therapy / Q000473:pathology; D002544:Cerebral Infarction / Q000188:drug therapy / Q000473:pathology; D002561:Cerebrovascular Disorders / Q000188:drug therapy* / Q000473:pathology; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D008274:Magnesium / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D001786:Blood Glucose; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D008274:Magnesium