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Journal of Neuroscience, Vol 9, 3720-3727, Copyright © 1989 by Society for Neuroscience
Riluzole, a novel antiglutamate, prevents memory loss and hippocampal neuronal damage in ischemic gerbils
C Malgouris, F Bardot, M Daniel, F Pellis, J Rataud, A Uzan, JC Blanchard and PM Laduron
Rhone-Poulenc Sante, Centre de Recherches de Gennevilliers, France.
The neuroprotective effects of riluzole, a novel antiglutamate, has been
demonstrated in a model of ischemia induced in female Mongolian gerbils by
transient bilateral carotid occlusion. Riluzole was administered at a dose
of 4 mg/kg, i.p., just before, 4 hr after, and for the 14 d following the
transient bilateral carotid occlusion (10 min). The functional sequelae of
ischemic damage were assessed using a memory test (passive avoidance) and
the extent of neuronal damage by histological examination and quantitative
autoradiography of muscarinic cholinergic receptors in the hippocampus. The
performance of the ischemic gerbils in the memory test was about half that
of control animals. This memory deficit was completely reversed in animals
treated with riluzole. This protective effect of riluzole was confirmed by
histological and autoradiographic studies. The neuronal degeneration of CA1
pyramidal cells in the hippocampus observed in the ischemic group was not
seen in the riluzole-treated animals, which resembled the control group.
This neuronal degeneration in the CA1 area was confirmed by a quantitative
measurement of muscarinic receptors: The binding was decreased by a third
in the lacunosum moleculare, the stratum oriens, and the stratum radiatum.
By contrast in riluzole-treated gerbils, this decrease was reversed by 50%.
Finally, a clear-cut correlation was found between the deficit in the
memory test and the decrease in muscarinic receptor binding in the CA1
fields. These results are compatible with the idea that glutamic acid may
be involved in the neuronal degeneration of the hippocampus following
ischemia, and could be foreseeable.(ABSTRACT TRUNCATED AT 250 WORDS)
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