Riluzole, a novel antiglutamate, prevents memory loss and hippocampal neuronal damage in ischemic gerbils.
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)
Malgouris
C
C
Rhône-Poulenc Santé, Centre de Recherches de Gennevilliers, France.
Bardot
F
F
Daniel
M
M
Pellis
F
F
Rataud
J
J
Uzan
A
A
Blanchard
J C
JC
Laduron
P M
PM
D000647:Amnesia / Q000517:prevention & control*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists; D005260:Female; D005849:Gerbillinae; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000502:physiology / Q000503:physiopathology*; D002546:Ischemic Attack, Transient / Q000503:physiopathology*; D008568:Memory / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism; D019782:Riluzole; D013844:Thiazoles / Q000494:pharmacology*
D018691:Excitatory Amino Acid Antagonists; D011976:Receptors, Muscarinic; D013844:Thiazoles; D011813:Quinuclidinyl Benzilate; D019782:Riluzole