Kainic acid neurotoxicity: in vivo test of two new non-N-methyl-D-aspartate receptor antagonists.
The possible neuroprotective effects of two new non-N-methyl-D-aspartate receptor antagonists were determined by quantitative light microscopy after intracerebral administration of kainic acid (KA) in two rat brain regions. KA alone or KA in combination with the antagonists alpha-amino-3-carboxy-methoxy-5-methyl-4-isoxazolepropionic acid (AMOA) and alpha-amino-2-(3-hydroxy-5-methyl-4-isoxazolyl)methyl-5-methyl-3 -oxo-4-isoxazoline-4-propionic acid (AMNH) were stereotaxically injected into the striatum or into the CA3 region of hippocampus. Seven days later neuropathological examination including cell counts was performed on paraffin sections from the two brain regions. In the striatum, AMOA almost completely attenuated KA-induced cell damage, whereas AMNH showed no protective effect. In the hippocampal CA3 region none of the test compounds possessed neuroprotective properties against KA. These results seem to be consistent with a difference in the mechanisms responsible for the neurotoxic action of KA in the hippocampus compared to the striatum.
Berg
M
M
PharmaBiotec Research Center, University of Copenhagen, Denmark.
Bruhn
T
T
Johansen
F F
FF
Krogsgaard-Larsen
P
P
Diemer
N H
NH
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003342:Corpus Striatum / Q000473:pathology; D006624:Hippocampus / Q000473:pathology; D007555:Isoxazoles / Q000494:pharmacology*; D007608:Kainic Acid / Q000037:antagonists & inhibitors / Q000633:toxicity*; D008297:Male; D009422:Nervous System Diseases / Q000139:chemically induced / Q000473:pathology* / Q000517:prevention & control; D011712:Pyramidal Tracts / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000031:analogs & derivatives*
D007555:Isoxazoles; D016194:Receptors, N-Methyl-D-Aspartate; C069453:alpha-amino-2-(3-hydroxy-5-methyl-4-isoxazolyl)methyl-5-methyl-3-oxo-4-isoxazoline-4-propionic acid; C069452:alpha-amino-3-carboxymethoxy-5-methyl-4-isoxazolepropionic acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D007608:Kainic Acid