Focal Cerebral Ischemia in the Cat: Pretreatment with a Competitive NMDA Receptor Antagonist, D-CPP-ene

Bullock, Ross; Graham, David I.; Chen, Min-Hsiung; Lowe, David J.; McCulloch, James

doi:10.1038/jcbfm.1990.120

Cited by 106 publications

(18 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…12 Furthermore, reduction in caudate injury was not significant in earlier studies with MK-801, whereas striatal protection was observed with dextromethorphan. 39 We observed 49% and 64% reductions in caudate injury at the 5-and 50-mg/kg doses, respectively.…”

Section: Discussionmentioning

confidence: 86%

“…- 12 However, efficacy of competitive NMDA antagonists administered at reperfusion after transient focal ischemia is unclear. The goal of the present study was to test the hypothesis that a competitive NMDA receptor antagonist decreases the volume of injury associated with 1 hour of transient focal ischemia when the drug is administered at two different doses 15 minutes before reperfusion.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Competitive N-methyl-D-aspartate receptor blockade reduces brain injury following transient focal ischemia in cats.

Nishikawa

Kirsch

Koehler

et al. 1994

Stroke

View full text Add to dashboard Cite

Background and PurposeWe 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 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 hemi-

show abstract

Section: Discussionmentioning

confidence: 86%

mentioning

confidence: 99%

Competitive N-methyl-D-aspartate receptor blockade reduces brain injury following transient focal ischemia in cats.

Nishikawa

Kirsch

Koehler

et al. 1994

Stroke

View full text Add to dashboard Cite

show abstract

“…This is because competitive and noncompetitive 7V-methyl-D-aspartate (NMDA) antagonists have been shown to reduce infarct size to about 50% of control even though MCA occlusion is maintained. 6 " 10 Comparable effects have been obtained with some calcium antagonists. 11 -12 In all these cases, pharmacological treatment reduced damage to neocortical tissue without affecting the lesion to the focal areas encompassing the dorsolateral part of the caudoputamen and the adjacent neocortical areas.…”

mentioning

confidence: 94%

Penumbral tissues salvaged by reperfusion following middle cerebral artery occlusion in rats.

Memezawa

Smith

Siesjö

1992

Stroke

425

208

View full text Add to dashboard Cite

Background and Purpose:The rat is now extensively used for studies on focal cerebral ischemia, and several novel pharmacological principles have been worked out in rat models of middle cerebral artery occlusion. The objective of the present study was to assess how ischemic tissue can be salvaged by reperfusion in a model of transient focal ischemia that gives infarction of both the caudoputamen and the neocortex.Methods: The middle cerebral artery of anesthetized rats was occluded for 15, 30, 60, 90, 120, or 180 minutes by an intraluminal filament, and recirculation was instituted for 7 days to allow assessment of the density and localization of ischemic brain damage using histopathologic techniques. Local cerebral blood flow was measured in separate animals to verify that removal of the filament was followed by adequate recirculation.Results: Following 15 minutes of middle cerebral artery occlusion seven of eight rats showed selective neuronal necrosis in the caudoputamen, while the neocortex was normal. After 30 minutes of occlusion, seven of eight animals had infarcts localized to the lateral caudoputamen, and four of eight had selective neuronal necrosis in the neocortex. Prolongation of the ischemia to 60 minutes induced cortical infarction in all eight rats. The infarct size increased progressively with increasing occlusion time, up to 120-180 minutes, when the infarcts were as extensive as those observed following 24 hours of permanent middle cerebral artery occlusion.Conclusions: The results demonstrate a time window for salvage of penumbral tissues by reperfusion that is shorter than that suggested on the basis of previous data in other species. The results probably reflect a lower collateral blood flow in the rat than in other species. This should be taken into account when the effect of pharmacological agents is studied in rats. (Stroke 1992;23:552-559)

show abstract

“…The physiological and pathological effects of glutamate in the CNS are mediated through its interaction with specific cell membrane receptors, of which the N-methyl-D-aspartate (NMDA), kainate, and AMPA subtypes are the best characterized [Monoghan et al, 1989]. The use of specific antagonists [Park et al, 1988;Monoghan et al, 1989;Bullock et al, 1990;Flood et al, 1990;Bashir et al, 1991;Tacconi et al, 1993;Hoffman et al, 1994] of the NMDA receptor support the role of receptor activation in LTP and hypoxic/ischemic cerebral injury. The NMDA-type glutamate receptor is a predominant mediator of excitotoxicity in the immature as compared to the adult brain due to overexpression of the receptor in the developing immature brain [Johnston, 1995].…”

Section: Introductionmentioning

confidence: 99%

NMDA receptor and neonatal hypoxic brain injury

Mishra

Fritz

Delivoria‐Papadopoulos

2001

Ment. Retard. Dev. Disabil. Res. Rev.

View full text Add to dashboard Cite

The NMDA-type glutamate receptor is a predominant mediator of excitotoxicity in the immature brain due to overexpression of the receptor in the developing brain. Within the development period however, the extent of NMDA receptor mediated processes including hypoxia-induced excitotoxicity may depend on the ontogeny of the NMDA receptor recognition and modulation sites, and subunits leading to altered function of the ion-channel comples. The function of the receptor may be modified by intracellular mechanisms such as phosphorylation/dephosphorylation, nitration, and generation of free radicals including nitric oxide. The susceptibility of the developing brain to hypoxia depends on several factors: the lipid composition of the brain cell membrane; the rate of membrane lipid peroxidation and the status of anti-oxidant defenses; the development and modulation of the NMDA receptor sites; the intracellular Ca(2+) influx mechanisms; expression of apoptotic and antiapoptotic genes such as Bax and Bcl-2; and the activation of initiator caspases and caspase-3, the "executioner" of cell death. The developmental status of these cellular mechanisms and their response to hypoxia determine the fate of the hypoxic cell in the developing brain in the fetus and the newborn.

show abstract

Focal Cerebral Ischemia in the Cat: Pretreatment with a Competitive NMDA Receptor Antagonist, D-CPP-ene

Cited by 106 publications

References 33 publications

Competitive N-methyl-D-aspartate receptor blockade reduces brain injury following transient focal ischemia in cats.

Competitive N-methyl-D-aspartate receptor blockade reduces brain injury following transient focal ischemia in cats.

Penumbral tissues salvaged by reperfusion following middle cerebral artery occlusion in rats.

NMDA receptor and neonatal hypoxic brain injury

Contact Info

Product

Resources

About