Competitive 7V-Methyl-D-aspartate receptor blockade reduces brain injury following transient focal ischemia in cats

Toshiaki Nishikawa, Jeffrey R. Kirsch, Raymond C Koehler, Masayuki Miyabe, Richard J. Traystman

Research output: Contribution to journalArticle

Abstract

Background and Purpose We tested the hypothesis that administration of the competitive N-methyl-D-aspartate (NMDA) receptor antagonist NPC 17742 (2R,4R,5S-[2-amino-4,5-(l,2-cyclohexyl)-7-phosphonoheptanoic acid]) during transient focal ischemia affects early postischemic brain injury. Methods Halothane-anesthetized cats underwent 1 hour of left middle cerebral artery occlusion plus 4 hours of reperfusion. Control cats received saline (n=7). Experimental cats were treated with NPC 17742 at a dose of 5 mg/kg IV from 45 minutes of ischemia to 15 minutes of reperfusion and 2.5 mg/kg per hour for 4 hours of re perfusion (NPC-5; n=7) or 50 mg/kg from 45 minutes of ischemia to 15 minutes of reperfusion and 25 mg/kg per hour for 4 hours of reperfusion (NPC-50; n=5). Results Microsphere-determined blood flow to the ipsilateral inferior temporal cortex and caudate nucleus decreased to the same extent during ischemia and recovered to the same extent during reperfusion in the three groups. Triphenyltetra-zolium-determined injury volume of ipsilateral cerebral hemi- sphere (saline, 24±8%; NPC-5, 4±2%; NPC-50, 5±2% of hemisphere; mean±SE) and caudate nucleus (saline, 72±6%; NPC-5, 37±10%; NPC-50, 26±4%) was less in cats treated with both doses of drug compared with cats treated with saline. Recovery of somatosensory evoked potential amplitude was incomplete and similar in all groups (saline, 36± 14%; NPC-5, 58±8%; NPC-50, 51 ±15% of baseline). Conclusions These data indicate that activation of NMDA receptors plays an important role in the mechanism of acute injury in both cortex and caudate after 1 hour of transient focal ischemia in the cat. Because NPC 17742 afforded protection when administered at the end of ischemia and during reperfusion, NMDA receptor activation during reperfusion may contribute to the progression of injury in ischemic border regions.

Original languageEnglish (US)
Pages (from-to)2258-2264
Number of pages7
JournalStroke
Volume25
Issue number11
StatePublished - 1994

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D-Aspartic Acid
Brain Injuries
Reperfusion
Cats
Ischemia
N-Methyl-D-Aspartate Receptors
Caudate Nucleus
Wounds and Injuries
Somatosensory Evoked Potentials
Middle Cerebral Artery Infarction
Halothane
Temporal Lobe
aspartic acid receptor
Microspheres
Perfusion
Acids
Pharmaceutical Preparations

Keywords

  • Cerebral blood flow
  • Evoked potentials
  • Excitatory amino acids
  • Middle cerebral artery occlusion
  • Somatosensory

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Advanced and Specialized Nursing
  • Neuroscience(all)

Cite this

Nishikawa, T., Kirsch, J. R., Koehler, R. C., Miyabe, M., & Traystman, R. J. (1994). Competitive 7V-Methyl-D-aspartate receptor blockade reduces brain injury following transient focal ischemia in cats. Stroke, 25(11), 2258-2264.

Competitive 7V-Methyl-D-aspartate receptor blockade reduces brain injury following transient focal ischemia in cats. / Nishikawa, Toshiaki; Kirsch, Jeffrey R.; Koehler, Raymond C; Miyabe, Masayuki; Traystman, Richard J.

In: Stroke, Vol. 25, No. 11, 1994, p. 2258-2264.

Research output: Contribution to journalArticle

Nishikawa, T, Kirsch, JR, Koehler, RC, Miyabe, M & Traystman, RJ 1994, 'Competitive 7V-Methyl-D-aspartate receptor blockade reduces brain injury following transient focal ischemia in cats', Stroke, vol. 25, no. 11, pp. 2258-2264.
Nishikawa, Toshiaki ; Kirsch, Jeffrey R. ; Koehler, Raymond C ; Miyabe, Masayuki ; Traystman, Richard J. / Competitive 7V-Methyl-D-aspartate receptor blockade reduces brain injury following transient focal ischemia in cats. In: Stroke. 1994 ; Vol. 25, No. 11. pp. 2258-2264.
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abstract = "Background and Purpose We tested the hypothesis that administration of the competitive N-methyl-D-aspartate (NMDA) receptor antagonist NPC 17742 (2R,4R,5S-[2-amino-4,5-(l,2-cyclohexyl)-7-phosphonoheptanoic acid]) during transient focal ischemia affects early postischemic brain injury. Methods Halothane-anesthetized cats underwent 1 hour of left middle cerebral artery occlusion plus 4 hours of reperfusion. Control cats received saline (n=7). Experimental cats were treated with NPC 17742 at a dose of 5 mg/kg IV from 45 minutes of ischemia to 15 minutes of reperfusion and 2.5 mg/kg per hour for 4 hours of re perfusion (NPC-5; n=7) or 50 mg/kg from 45 minutes of ischemia to 15 minutes of reperfusion and 25 mg/kg per hour for 4 hours of reperfusion (NPC-50; n=5). Results Microsphere-determined blood flow to the ipsilateral inferior temporal cortex and caudate nucleus decreased to the same extent during ischemia and recovered to the same extent during reperfusion in the three groups. Triphenyltetra-zolium-determined injury volume of ipsilateral cerebral hemi- sphere (saline, 24±8{\%}; NPC-5, 4±2{\%}; NPC-50, 5±2{\%} of hemisphere; mean±SE) and caudate nucleus (saline, 72±6{\%}; NPC-5, 37±10{\%}; NPC-50, 26±4{\%}) was less in cats treated with both doses of drug compared with cats treated with saline. Recovery of somatosensory evoked potential amplitude was incomplete and similar in all groups (saline, 36± 14{\%}; NPC-5, 58±8{\%}; NPC-50, 51 ±15{\%} of baseline). Conclusions These data indicate that activation of NMDA receptors plays an important role in the mechanism of acute injury in both cortex and caudate after 1 hour of transient focal ischemia in the cat. Because NPC 17742 afforded protection when administered at the end of ischemia and during reperfusion, NMDA receptor activation during reperfusion may contribute to the progression of injury in ischemic border regions.",
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T1 - Competitive 7V-Methyl-D-aspartate receptor blockade reduces brain injury following transient focal ischemia in cats

AU - Nishikawa, Toshiaki

AU - Kirsch, Jeffrey R.

AU - Koehler, Raymond C

AU - Miyabe, Masayuki

AU - Traystman, Richard J.

PY - 1994

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N2 - Background and Purpose We tested the hypothesis that administration of the competitive N-methyl-D-aspartate (NMDA) receptor antagonist NPC 17742 (2R,4R,5S-[2-amino-4,5-(l,2-cyclohexyl)-7-phosphonoheptanoic acid]) during transient focal ischemia affects early postischemic brain injury. Methods Halothane-anesthetized cats underwent 1 hour of left middle cerebral artery occlusion plus 4 hours of reperfusion. Control cats received saline (n=7). Experimental cats were treated with NPC 17742 at a dose of 5 mg/kg IV from 45 minutes of ischemia to 15 minutes of reperfusion and 2.5 mg/kg per hour for 4 hours of re perfusion (NPC-5; n=7) or 50 mg/kg from 45 minutes of ischemia to 15 minutes of reperfusion and 25 mg/kg per hour for 4 hours of reperfusion (NPC-50; n=5). Results Microsphere-determined blood flow to the ipsilateral inferior temporal cortex and caudate nucleus decreased to the same extent during ischemia and recovered to the same extent during reperfusion in the three groups. Triphenyltetra-zolium-determined injury volume of ipsilateral cerebral hemi- sphere (saline, 24±8%; NPC-5, 4±2%; NPC-50, 5±2% of hemisphere; mean±SE) and caudate nucleus (saline, 72±6%; NPC-5, 37±10%; NPC-50, 26±4%) was less in cats treated with both doses of drug compared with cats treated with saline. Recovery of somatosensory evoked potential amplitude was incomplete and similar in all groups (saline, 36± 14%; NPC-5, 58±8%; NPC-50, 51 ±15% of baseline). Conclusions These data indicate that activation of NMDA receptors plays an important role in the mechanism of acute injury in both cortex and caudate after 1 hour of transient focal ischemia in the cat. Because NPC 17742 afforded protection when administered at the end of ischemia and during reperfusion, NMDA receptor activation during reperfusion may contribute to the progression of injury in ischemic border regions.

AB - Background and Purpose We tested the hypothesis that administration of the competitive N-methyl-D-aspartate (NMDA) receptor antagonist NPC 17742 (2R,4R,5S-[2-amino-4,5-(l,2-cyclohexyl)-7-phosphonoheptanoic acid]) during transient focal ischemia affects early postischemic brain injury. Methods Halothane-anesthetized cats underwent 1 hour of left middle cerebral artery occlusion plus 4 hours of reperfusion. Control cats received saline (n=7). Experimental cats were treated with NPC 17742 at a dose of 5 mg/kg IV from 45 minutes of ischemia to 15 minutes of reperfusion and 2.5 mg/kg per hour for 4 hours of re perfusion (NPC-5; n=7) or 50 mg/kg from 45 minutes of ischemia to 15 minutes of reperfusion and 25 mg/kg per hour for 4 hours of reperfusion (NPC-50; n=5). Results Microsphere-determined blood flow to the ipsilateral inferior temporal cortex and caudate nucleus decreased to the same extent during ischemia and recovered to the same extent during reperfusion in the three groups. Triphenyltetra-zolium-determined injury volume of ipsilateral cerebral hemi- sphere (saline, 24±8%; NPC-5, 4±2%; NPC-50, 5±2% of hemisphere; mean±SE) and caudate nucleus (saline, 72±6%; NPC-5, 37±10%; NPC-50, 26±4%) was less in cats treated with both doses of drug compared with cats treated with saline. Recovery of somatosensory evoked potential amplitude was incomplete and similar in all groups (saline, 36± 14%; NPC-5, 58±8%; NPC-50, 51 ±15% of baseline). Conclusions These data indicate that activation of NMDA receptors plays an important role in the mechanism of acute injury in both cortex and caudate after 1 hour of transient focal ischemia in the cat. Because NPC 17742 afforded protection when administered at the end of ischemia and during reperfusion, NMDA receptor activation during reperfusion may contribute to the progression of injury in ischemic border regions.

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