Effects of combined glutamate and platelet-activating factor inhibition on the outcome of focal cerebral ischaemia : an initial screening study

Since both glutamate excitotoxicity and inflammatory responses have been implicated in ischaemic neuronal death, we questioned whether joint inhibition of both processes would be more neuroprotective than either on its own. Therefore we assessed the effects of combined inhibition of both glutamate r...

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Bibliographic Details
Published in:Metabolic brain disease 1997-09, Vol.12 (3), p.237-249
Main Authors: ASPEY, B. S, ALP, M. S, PATEL, Y, HARRISON, M. J. G
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Brain Ischemia - complications
Brain Ischemia - physiopathology
Cerebral Infarction - pathology
Drug Combinations
Glutamic Acid - metabolism
Leucine - analogs & derivatives
Leucine - pharmacology
Male
Medical sciences
Movement Disorders - etiology
Movement Disorders - physiopathology
Neuropharmacology
Neuroprotective agent
Neuroprotective Agents - pharmacology
Periaqueductal Gray - pathology
Pharmacology. Drug treatments
Piperazines - pharmacology
Platelet Activating Factor - antagonists & inhibitors
Platelet Membrane Glycoproteins - antagonists & inhibitors
Pyrimidines - pharmacology
Rats
Rats, Sprague-Dawley
Receptors, Cell Surface
Receptors, G-Protein-Coupled
Sodium Channel Blockers
Time Factors
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Summary:Since both glutamate excitotoxicity and inflammatory responses have been implicated in ischaemic neuronal death, we questioned whether joint inhibition of both processes would be more neuroprotective than either on its own. Therefore we assessed the effects of combined inhibition of both glutamate release (with a use-dependant sodium channel blocker, 619C89) and inflammatory processes (with a platelet-activating factor (PAF) receptor antagonist, BB-823) on the degree of motor deficit and the extent of cerebral (cortical and sub-cortical grey matter) infarction produced by middle cerebral artery occlusion (MCAO) in the rat, and compared results to appropriate single agent, vehicle and positive controls. The combination of both agents produced the greatest reduction in motor deficit, but the effect was only significant (p
ISSN:0885-7490
1573-7365
DOI:10.1007/bf02674616