Hostname: page-component-586b7cd67f-t7czq Total loading time: 0 Render date: 2024-11-23T20:50:18.582Z Has data issue: false hasContentIssue false
  • English
  • Français

NMDA Receptor Blockade and Spinal Cord Ischemia Due to Aortic Crossclamping in the Rat Model

Published online by Cambridge University Press:  18 September 2015

F. Follis ,
K. Miller ,
O. U. Scremin ,
S. Pett ,
R. Kessler  and
J. Wernly
F. Follis*
Affiliation:
Department of Thoracic and Cardiothoracic Surgery, University of California Los Angeles School of Medicine, Los Angeles
K. Miller
Affiliation:
Department of Thoracic and Cardiothoracic Surgery, University of California Los Angeles School of Medicine, Los Angeles
O. U. Scremin
Affiliation:
University of New Mexico and West Los Angeles V.A. Medical Center and Department of Physiology, University of California Los Angeles School of Medicine, Los Angeles
S. Pett
Affiliation:
Department of Thoracic and Cardiothoracic Surgery, University of California Los Angeles School of Medicine, Los Angeles
R. Kessler
Affiliation:
Department of Thoracic and Cardiothoracic Surgery, University of California Los Angeles School of Medicine, Los Angeles
J. Wernly
Affiliation:
Department of Thoracic and Cardiothoracic Surgery, University of California Los Angeles School of Medicine, Los Angeles
*
University of New Mexico, Department of Thoracic and Cardiovascular Surgery, 2211 Lomas Blvd., Albuquerque, New Mexico, USA 87131
Rights & Permissions [Opens in a new window]

Abstract:

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

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 MgS04 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 μL of normal saline (SA n = 16), MgS04 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 MgS04 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.

Type
Original Articles
Information
Canadian Journal of Neurological Sciences , Volume 21 , Issue 3 , August 1994 , pp. 227 - 232
Copyright
Copyright © Canadian Neurological Sciences Federation 1994

References

1.Rothman, SM, Olney, JW.Excitotoxicity and the NMDA receptor. Trends Neurosci 1987; 10(7): 299–302.CrossRefGoogle Scholar
2.Rothman, SM, Olney, JW.Glutamate and the pathophysiology of hypoxic-ischemic brain damage. Ann Neurol 1986; 19(2): 105–111.CrossRefGoogle ScholarPubMed
3.Baudry, M, Bundman, MC, Smith, EK, Lynch, GS.Micromolar calcium stimulates proteolysis and glutamate binding in rat brain synaptic membranes. Science 1981; 212: 937–938.CrossRefGoogle ScholarPubMed
4.Gilbert, DS, Newby, BJ, Anderton, BH.Neurofilament disguise, destruction and discipline. Nature 1975; 256: 586–589.CrossRefGoogle ScholarPubMed
5.Farber, JL, Chien, KR, Mittnacht, S.Myocardial ischemia: the pathogenesis of irreversible cell injury in ischemia. Am J Pathol 1981; 102(2): 271–281.Google ScholarPubMed
6.Wolfe, LS.Eicosanoids: prostaglandins, thromboxanes, leukotrienes and other derivatives of carbon-20 unsaturated fatty acids. J Neurochem 1982; 38(1): 1–14.CrossRefGoogle ScholarPubMed
7.LeMay, DR, Neal, S, Zelenock, GB, D’Alecy, LG.Paraplegia in the rat induced by aortic cross-clamping: model characterization and glucose exacerbation of neurologic deficit. J Vase Surg 1987; 6(4): 383–390.CrossRefGoogle ScholarPubMed
8.LeMay, DR, Lu, AC, Zelenock, GB, D’Alecy, LG.Insulin administration protects from paraplegia in the rat aortic occlusion model. J Surg Res 1988; 44: 352–358.CrossRefGoogle ScholarPubMed
9.Follis, F, Scremin, OU, Blisard, KS, et al. Selective vulnerability of white matter during spinal cord ischemia. J Cereb Blood Flow Metab 1993; 13(1): 170–178.CrossRefGoogle ScholarPubMed
10.SAS Institute Inc. SAS/STAT User’s Guide, Version 6, Fourth Edition, Volume 2. Cary, NCSAS Institute Inc., 1989.Google Scholar
11.Gill, R, Foster, AC, Woodruff, GN.Systemic administration of MK-801 protects against ischemia-induced hippocampal neurode-generation in the gerbil. J Neurosci 1987; 7(10): 3343–3349.CrossRefGoogle Scholar
12.Gill, R, Foster, AC, Woodruff, GN.MK-801 is neuroprotective in gerbils when administered during the post-ischaemic period. Neuroscience 1988; 25(3): 847–855.CrossRefGoogle ScholarPubMed
13.Svensson, LG, Grum, DF, Bednarski, M.Appraisal of cerebrospinal fluid alterations during aortic surgery with intrathecal papaverine administration and cerebrospinal fluid drainage. J Vase Surg 1990; 11:423–429.CrossRefGoogle ScholarPubMed
14.Breckwoldt, WL, Genco, CM, Connolly, RJ, Cleveland, RJ, Diehl, JT.Spinal cord protection during aortic occlusion: efficacy of intrathecal tetracaine. Ann Thorac Surg 1991; 51: 959–963.CrossRefGoogle ScholarPubMed
15.Svensson, LG, von Ritter, CM, Groeneveld, HT.Cross-clamping of the thoracic aorta: influence of aortic shunts, laminectomy, papaverine, calcium channel blocker, allopurinol and superoxide dismutase on spinal cord blood flow and paraplegia in baboons. Ann Surg 1986; 204:38–47.CrossRefGoogle ScholarPubMed
16.Vacanti, FX, Ames III, A.Mild hypothermia and Mg2+ protect against irreversible damage during CNS ischemia. Stroke 1984; 15(4): 695–698.CrossRefGoogle Scholar
17.Robertson, CS, Foltz, R, Grossman, RG, Goodman, JC.Protection against experimental ischemic spinal cord injury. J Neurosurg 1986; 64(4): 633–642.CrossRefGoogle ScholarPubMed
18.Altura, BM, Altura, BT.Magnesium ions and contraction of vascular smooth muscles: relationship to some vascular diseases. Fed Proc 1981; 40(12): 2672–2679.Google ScholarPubMed
19.Kochhar, A, Zivin, JA, Lyden, PD, Mazzarella, V.Glutamate antagonist therapy reduces neurologic deficits produced by focal central nervous system ischemia. Arch Neurol 1988; 45: 148–153.CrossRefGoogle ScholarPubMed
20.Yaksh, TL, Rudy, TA.Chronic catheterization of the spinal subarachnoid space. Physiol Behav 1976; 17(6): 1031–1036.CrossRefGoogle ScholarPubMed
21.Simon, RP, Swan, JH, Griffiths, T, Meldrum, BS.Blockade of N-methyl-D-aspartate receptors may protect against ischemic damage in the brain. Science 1984; 226: 850–852.CrossRefGoogle ScholarPubMed
22.Evans, RH, Watkins, JC.Specific antagonism of excitant amino acids in the isolated spinal cord of the neonatal rat. Eur J Pharmacol 1978; 50(2): 123–129.CrossRefGoogle ScholarPubMed
23.Davies, J, Watkins, JC.Selective antagonism of amino acid-induced and synaptic excitation in the cat spinal cord. J Physiol 1979; 297:621–635.CrossRefGoogle ScholarPubMed
24.Lodge, D, Headley, PM, Curtis, DR.Selective antagonism by D-a-aminoadipate of amino acid and synaptic excitation of cat spinal neurons. Brain Res 1978; 152(3): 603–608.CrossRefGoogle ScholarPubMed
25.Goldberg, MP, Viseskul, V, Choi, DW.Phencyclidine receptor ligands attenuate cortical neuronal injury after N-methyl-D-aspartate exposure or hypoxia. J Pharmacol Exp Ther 1988; 245(3): 1081–1087.Google ScholarPubMed
26.Clark, GD, Rothman, SM.Blockade of excitatory amino acid receptors protects anoxic hippocampal slices. Neuroscience 1987; 21(3): 665–671.CrossRefGoogle ScholarPubMed
27.Boast, CA, Gerhardt, SC, Pastor, G, et al. The N-methyl-D-aspartate antagonists CGS 19755 and CPP reduce ischemic brain damage in gerbils. Brain Res 1988; 442(2): 345–348.CrossRefGoogle ScholarPubMed
28.Yum, SW, Faden, AI.Comparison of the neuroprotective effects of the N-methyl-D-aspartate antagonist MK-801 and the opiate-receptor antagonist nalmefene in experimental spinal cord ischemia. Arch Neurol 1990; 47(3): 277–281.CrossRefGoogle ScholarPubMed
29.Fleischer, JE, Tateishi, A, Drummond, JC, et al. MK-801, an excitatory amino acid antagonist, does not improve neurologic outcome following cardiac arrest in cats. J Cereb Blood Flow Metab 1989; 9(6): 795–804.CrossRefGoogle Scholar
30.Sterz, F, Leonoy, Y, Safar, P, et al. Effect of excitatory amino acid receptor blocker, MK-801, on overall neurologic and morphologic outcome after prolonged cardiac arrest in dogs. Anesthesiology 1989; 71(6): 907–918.CrossRefGoogle ScholarPubMed
31.LeBlanc, MH, Vig, V, Smith, B, et al. MK-801 does not protect against hypoxic-ischemic brain injury in piglets. Stroke 1991; 22(10): 1270–1275.CrossRefGoogle Scholar