The N-methyl-d-aspartate antagonists CGS 19755 and CPP reduce ischemic brain damage in gerbils

Boast, Carl A.; Gerhardt, Susan; Pastor, Gary; Lehmann, John; Étienne, Pierre; Liebman, Jeffrey M.

doi:10.1016/0006-8993(88)91522-3

Cited by 240 publications

(69 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Kynurenic acid is a competitive NMDA antagonist but, in addition, blocks the gly cine site in the NMDA receptor complex as well as non-NMDA receptors (quisqualate and kainate) (Perkins and Stone, 1982;Birch et al, 1988), which may be involved in excitotoxic damage to neurons (Frandsen et al, 1989). CPP and CGS 19755 reduce ischemic damage in a gerbil model (Boast et al, 1988), but the susceptibility of this model to post ischemic seizures and the potency of NMDA antag onists as anticonvulsants (Meldrum, 1985;Leh mann et al, 1988) compromise these data. The present report provides evidence that a competitive NMDA antagonist, with therapeutic potential, is ca pable of markedly reducing cortical damage in a gyrencephalic model of focal cerebral ischemia.…”

Section: Discussionmentioning

confidence: 99%

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

Bullock

Graham

Chen

et al. 1990

J Cereb Blood Flow Metab

106

View full text Add to dashboard Cite

Summary:The effects of the competitive N methyl-o-aspartate (NMD A) receptor antagonist 0-(E)-4-(3-phosphonoprop-2-enyl)piperazine-2-carboxylic acid (o-CPP-ene; SDZ EAA 494) upon ischemic brain damage have been examined in anesthetized cats. Focal cerebral ischemia was produced by permanent occlusion of the middle cerebral artery (MCA) and the animals were killed 6 h later. The amount of early ischemic brain dam age was assessed in coronal sections at 16 predetermined stereotaxic planes. Pretreatment with o-CPP-ene (15 mg/ kg i. v. followed by continuous infusion at 0.17 mg/kg/min Excessive activation of glutamate receptors ap pears to be a crucial factor in the sequence of cel lular events leading to irreversible ischemic damage to neurons (Meldrum, 1985;Rothman and Olney, 1986). There is now considerable evidence that treatment with glutamate receptor antagonists, par ticularly antagonists of the N-methyl-D-aspartate (NMDA) receptor subtype, can reduce ischemic

show abstract

Section: Discussionmentioning

confidence: 99%

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

Bullock

Graham

Chen

et al. 1990

J Cereb Blood Flow Metab

106

View full text Add to dashboard Cite

show abstract

“…Gluta mate antagonists are therefore considered a candidate therapy for the treatment of acute stroke. Numerous studies on the neuroprotective effect of N-methyl-D aspartate (NMDA)-type glutamate-receptor antagonists have been reported (2)(3)(4)(5)(6)(7). However, the use of NMDA receptor antagonists is limited because of side effects they produce including psychotomimetic action (8), learn ing impairment (9) and vacuolization of cerebrocortical neurons (10, 11).…”

Section: Abstract-mentioning

confidence: 99%

Neuroprotective Effect of YM9OK, an AMPA-Receptor Antagonist,against Delayed Neuronal Death Induced by Transient Global Cerebral Ischemia in Gerbils and Rats.

Kawasaki-Yatsugi¹,

Yatsugi²,

Koshiya³

et al. 1997

Jpn.J.Pharmacol

View full text Add to dashboard Cite

show abstract

“…Instead, the onus of this injury appears to rest on both NMDA and non-NMDA receptor-mediated mechanisms during the postischemic period (Sheardown et al, 1990;Nellgard and Wieloch, 199 l), when EAA levels and tissue pH have normalized, NMDA receptors regain function, and metabolism recovers. This may help explain why NMDA-receptor antagonists administered well before transient ischemia are generally ineffective as neuroprotective agents (for review, see Buchan,I990), whereas deafferentation or administration of NMDA-receptor antagonists during the reperfusion period can reduce neuronal injury (Boast et al, 1987(Boast et al, , 1988Johansen et al, 1987;Gill et al, 1988).…”

Section: An Excitotoxic Paradoxmentioning

confidence: 99%

Evolving Concepts About the Role of Acidosis in Ischemic Neuropathology

Tombaugh

Sapolsky

1993

Journal of Neurochemistry

188

109

View full text Add to dashboard Cite

Cerebral ischemia is one of the most common neurological insults. Many pathological events are undoubtedly triggered by ischemia, but only recently has it become accepted that ischemic cell injury arises from a complex interaction between multiple biochemical cascades. Tissue acidosis is a well established feature of ischemic brain tissue, but its role in ischemic neuropathology is still not fully understood. Within the last few years, new evidence has challenged the historically negative view of acidosis and suggests that it may play more of a beneficial role than previously thought. This review reintroduces the concept of acidosis to ischemic brain injury and presents some new perspectives on its neuroprotective potential. Key Words: Ischemia-infarction-Lactic acidosis-Excitotoxicity-Hippocampus-Selective neuronal necrosis -Energy metabolism. Experimental work aimed at understanding ischemic brain injury has highlighted numerous biochemical events that may mediate cell damage. Among these, tissue acidosis has received considerable attention. The history of the acidotic concept in ischemia research forms somewhat of an arch. A number of decades ago, cerebral acidosis was shown first to be a correlate of gross ischemic brain damage and was viewed later as a cause. At the height of interest in this topic, acidosis was considered among the principal mechanisms by which ischemic damage occurs (Myers, 1979;Siesjo, 1988~). Even so, it was clear that "cerebral ischemia" was not a single disease but any insult that involved a partial or complete reduction in cerebral blood flow. Various animal models of both focal and global ischemia have been widely used to study ischemic injury, but the question of whether tissue acidosis satisfactorily explains or even contributes to all forms of ischemic brain injury has never been formally addressed.Though acidosis is generally believed to underlie cerebral infarction, mounting evidence has suggested that acidosis does not contribute to the selective neuronal necrosis that occurs after transient ischemia or in the penumbra of developing infarcts. Not surprisingly, the earlier bias toward acidosis as a neurotoxic mechanism has waned. In this review, we briefly examine the evolution of the acidosis concept. We then focus on a recent and surprising series of in vitro observations suggesting that moderate acidosis may actually play a neuroprotective role during ischemia. We then discuss a striking and paradoxical implication of these data regarding the time course and possible mediators of selective neuronal injury following ischemia. THE TRADITIONAL BELIEF IN THE ACIDOTIC ROUTE OF ISCHEMIC DAMAGESupported by varying degrees of experimental evidence, many distinct mechanisms have been proposed to explain ischemic brain injury; of these, the concept of acidotic damage is perhaps the oldest. Early work suggested that metabolic acidosis, caused by continued glycolysis, was responsible for the severe tissue disruption seen in the postmortem brain (Friede and van Houten, 1961). D...

show abstract

The N-methyl-d-aspartate antagonists CGS 19755 and CPP reduce ischemic brain damage in gerbils

Cited by 240 publications

References 11 publications

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

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

Neuroprotective Effect of YM9OK, an AMPA-Receptor Antagonist,against Delayed Neuronal Death Induced by Transient Global Cerebral Ischemia in Gerbils and Rats.

Evolving Concepts About the Role of Acidosis in Ischemic Neuropathology

Contact Info

Product

Resources

About