Faculty Collaboration Database

Competitive N-methyl-D-aspartate receptor blockade reduces brain injury following transient focal ischemia in cats. Stroke 1994 Nov;25(11):2258-64

Date

11/01/1994

Pubmed ID

7526489

DOI

10.1161/01.str.25.11.2258

Scopus ID

2-s2.0-0028032883 (requires institutional sign-in at Scopus site)   28 Citations

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-(1,2-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 reperfusion (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. Triphenyltetrazolium-determined injury volume of ipsilateral cerebral hemisphere (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.

Author List

Nishikawa T, Kirsch JR, Koehler RC, Miyabe M, Traystman RJ

MESH terms used to index this publication - Major topics in bold

Amino Acids
Animals
Brain
Cats
Cerebrovascular Circulation
Drug Administration Schedule
Evoked Potentials, Somatosensory
Female
Ischemic Attack, Transient
Microspheres
Receptors, N-Methyl-D-Aspartate
Staining and Labeling
Tetrazolium Salts
Time Factors