NMDA receptor blockade and spinal cord ischemia due to aortic crossclamping in the rat model.
Recent brain research proposes that, during ischemia, synaptically released excitatory amino acid neurotransmitters accumulate at toxic concentrations with ensuing neuronal death. Their action is mediated by the receptor subtype N-methyl-D-aspartate (NMDA). The protective effect of NMDA receptor blockade with intrathecal MgSO4 and MK-801 was investigated during spinal cord ischemia induced by aortic occlusion of 12 minutes. Male Sprague-Dawley rats, 250-300g, underwent intrathecal administration of 20 microL of normal saline (SA n = 16), MgSO4 1M (MG n = 16), or MK-801, 25 mM solutions (MK n = 16) in a randomized order. After 2 hours, the animals underwent occlusion of the thoracic aorta and subclavian arteries for 12 min. An additional control group (CO n = 16) underwent occlusion for 12 minutes, without intrathecal injection. The animals were scored according to their functional performance (LS = lesion score) each day for four days by a blinded observer. Mean LS were calculated for each group at a given day. Treatment and control groups were not different at day 1 (P = 0.302). Group MG was improved from groups SA (P = < 0.0039) and CO (P = < 0.0048) at day 4. This study demonstrates that although intrathecal NMDA receptor blockade with MgSO4 or MK-801 does not prevent paraplegia due to spinal cord ischemia in the rat, it could however influence the rate of recovery after ischemic injury.
Follis
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Department of Thoracic and Cardiothoracic Surgery, University of New Mexico, Albuquerque 87131.
Miller
K
K
Scremin
O U
OU
Pett
S
S
Kessler
R
R
Wernly
J
J
D000818:Animals; D001013:Aorta, Thoracic; D003250:Constriction; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000494:pharmacology; D007278:Injections, Spinal; D007511:Ischemia / Q000473:pathology*; D008278:Magnesium Sulfate / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D009460:Neurologic Examination; D010865:Pilot Projects; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012039:Regional Blood Flow; D013116:Spinal Cord / Q000098:blood supply* / Q000473:pathology
D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D008278:Magnesium Sulfate