Effects of an A1 adenosine receptor agonist on the neurochemical, behavioral and histological consequences of ischemia.
Untreated rats and rats given the A1 receptor adenosine agonist, R-phenylisopropyladenosine (R-PIA), were subjected to four vessel ischemia. The effect of R-PIA on hippocampal amino acid release, hippocampal neuronal damage, exploratory behavior, learning capacity and global neurological score were evaluated. R-PIA decreased by half the glutamate released during ischemia and improved the global neurological scores 3, 24, 48, 78 h and 7 days after ischemia. But R-PIA had no effect on taurine/GABA release (during ischemia), hippocampal neuronal damage (7 days post-ischemia), exploratory behavior (48 h post-ischemia) or learning capacity (7 days post-ischemia). Thus, a decrease in glutamate release by R-PIA is not systematically correlated with an improvement of histological damage or learning capacity. Reduced glutamate release is not therefore a sufficient criterion on which to evaluate the neuroprotective capacity of a drug.
Laboratoire de Recherches Cérébrovasculaires, URA 641 CNRS, Faculté de Médecine Villemin, UFR Lariboisière-Saint-Louis, Université Paris, VII, France.
A
A
Héron
D
D
Lekieffre
E
E
Le Peillet
F
F
Lasbennes
J
J
Seylaz
M
M
Plotkine
R G
RG
Boulu
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D005106:Exploratory Behavior / Q000187:drug effects*; D005971:Glutamates / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D007858:Learning / Q000187:drug effects*; D008297:Male; D017551:Microdialysis; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010660:Phenylisopropyladenosine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000502:physiology*; D013654:Taurine / Q000378:metabolism; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000596:Amino Acids; D005971:Glutamates; D018047:Receptors, Purinergic P1; D013654:Taurine; D010660:Phenylisopropyladenosine; D005680:gamma-Aminobutyric Acid