T. Nishikawa et al., COMPETITIVE N-METHYL-D-ASPARTATE RECEPTOR BLOCKADE REDUCES BRAIN INJURY FOLLOWING TRANSIENT FOCAL ISCHEMIA IN CATS, Stroke, 25(11), 1994, pp. 2258-2264
Background and Purpose We tested the hypothesis that administration of
the competitive N-methyl-D-aspartate (NMDA) receptor antagonist NPC 1
7742 [2-amino-4,5-(1,2-cyclohexyl)-7-phosphonoheptanoic acid]) during
transient focal ischemia affects early postischemic brain injury. Meth
ods Halothane-anesthetized cats underwent 1 hour of left middle cerebr
al 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 reperfusio
n 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 Micr
osphere-determined blood how to the ipsilateral inferior temporal cort
ex and caudate nucleus decreased to the same extent during ischemia an
d 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 hemisph
ere; mean+/-SE) and caudate nucleus (saline, 72+/-6%; NPC-5, 37+/-10%s
NPC-50, 26+/-4%) was less in cats treated with both doses of drug com
pared 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 T
hese data indicate that activation of NMDA receptors plays an importan
t role in the mechanism of acute injury in both cortex and caudate aft
er 1 hour of transient focal ischemia in the cat. Because NPC 17742 af
forded protection when administered at the end of ischemia and during
reperfusion, NMDA receptor activation during reperfusion may contribut
e to the progression of injury in ischemic border regions.