Abstract
We studied the effects of a neuroprotector, riluzole, on the evoked mass activity of spinal neuronal mechanisms and on action potentials (APs) recorded from the sciatic nerve in intact rats and rats with the manifestations of postdenervational and 4-aminopyridine (4-AP)-induced hyperreflexia, as well as in animals in the superreflexia state (induced by combined action of denervation and 4-AP). We measured the parameters of monosynaptic reflex discharges (monosynaptic reflexes, MRs) recorded from the ventral root (VR), of the spinal dorsal surface potential (DSPs), and of mass APs evoked in afferent and efferent fibers of the SN before and 10, 30, 60, and 120 min after injection of riluzole. It was found that in intact animals riluzole significantly (by 60–70%) decreased the amplitude of VR MRs and those of the afferent peak and N1 component of DSPs. Riluzole exerted smaller suppressive effects on mass APs in the afferent fibers of the SN; the effect on APs in the SN efferent fibers was the minimum (a 4 to 5% decrease). Under conditions of increased sensitivity of the motoneuronal postsynaptic membrane to the transmitter (postdenervational hyperreflexia) and an increased release of glutamate from presynaptic elements (4-AP-induced hyperreflexia), as well as under superreflexia conditions, the dynamics of suppression of the evoked spinal activity by riluzole showed relatively moderate differences from those in intact animals. Under the above conditions, riluzole in the same manner decreased the amplitude of VR MRs. In the superreflexia state, the agent blocked the development of additional components of these dramatically increased potentials (in the above state, their amplitude increased by nearly nine times, on average, and this resulted in the generation of such components). We believe that the inhibitory effect of riluzole on glutamatergic neurotransmission in the spinal cord is based, first of all, on blocking of excitation in afferent presynaptic terminals. The possibility to use riluzole for correction of abnormally increased hyperexcitability of the spinal neuronal systems is discussed.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
A. Yu. Bespalov and É. É. Zvartau, Neuropsycho-pharmacology of Antagonists of NMDA Receptors [in Russian], Nevskii Dialekt, Saint Petersburg (2000).
J. Scárlato, “Amyotrophic lateral sclerosis: from pathological mechanism to patient care,” J. Neurol., 244,Suppl. 2, S1–S2 (1977).
P. J. Show and P. G. Ince, “Glutamate excitotoxicity and amyotrophic lateral sclerosis,” J. Neurol., 244,Suppl. 2, S3–S14 (1997).
E. A. Makii and I. Ya. Serdyuchenko, “Evoked activity of spinal neurons within early period after transection of the sciatic nerve in albino rats,” Neirofiziologiya, 24, No. 3, 306–314 (1992).
E. A. Makii, P. A. Nerush, and A. G. Rodinskii, “Segmental reflex activity under conditions of superreflexia induced by the action of drugs exceeding the excitability of the spinal cord,” Neurophysiology, 33, No. 2, 120–127 (2000).
E. A. Makii and I. A. Krayushkina, “Peculiarities of spinal hyperreflexia after simultaneously combined transection of the sciatic nerve and chordotomy in rats,” Neurophysiology, 26, No. 3, 165–169 (1994).
R. Stephen, “Excitatory synaptic transmission in the central nervous system,” Neurosci. Lett., Suppl., No. 27, 2–6 (1987).
G. F. Lakin, Biometrics [in Russian], Vysshaya Shkola, Moscow (1990).
Yu. I. Ivanov and O. N. Pogorelyuk, Statistical Processing of the Results of Medical/Biological Studies using Programmed Microcalculators [in Russian], Meditsina, Moscow (1990).
Yu. M. Kozhem’yakin, O. S. Khromov, M. A. Filonenko, and G. A. Sairetdinova, Scientific/Practical Recommendations for the Care of, and Experimental Work with, Laboratory Animals [in Russian], Kyiv (2002).
D. Martin, M. A. Thompson, and J. V. Nadler, “The neuroprotective agent riluzole inhibits release of glutamate and aspartate from slices of hippocampal area CA1,” Eur. J. Pharmacol., 250, No. 4, 473–476 (1993).
A. K. Florov, On the Genesis of the Dorsal Surface Potential of the Spinal Cord [in Russian], Abstr. of Cand. Thesis, Biol. Sci., Dnepropetrovsk (1966).
I. Ya. Serdyuchenko, P. I. Syabro, and E. A. Makii, “Electrical responses of the ventral roots to stimulation of the medullary pyramids and labyrinth in animals with a denervated limb,” Fiziol. Zh., 29, No. 6, 679–683 (1982).
O. G. Rodinskii, “An increase in the excitability of spinal motoneurons in albino rats after transection of the sciatic nerve is of a postsynaptic nature,” Med. Perspektivy, 9, No. 4, 5–11 (2004).
P. M. Mantulo, E. A. Makii, and I. Ya. Serdyuchenko, “Monosynaptic reflex responses after thyroidectomy or introduction of aurantine,” Fiziol. Zh., 29, No. 2, 145–149 (1982).
M. V. Kopanitsa, “Extrasynaptic receptors of neurotransmitters: distribution, mechanisms of activation, and physiological role,” Neurophysiology, 29, No. 6, 357–365 (1997).
E. A. Makii and A. G. Rodinskii, “Evoked activity in nerve trunks of the rat: 4-aminopyridine-induced modifications,” Neurophysiology, 35, No. 5, 371–377 (2003).
E. Benoit and D. Escande, “Riluzole specifically blocks inactive Na+ channels in myelinated nerve fibers,” Pflügers Arch., 419, No. 5, 603–607 (1991).
Author information
Authors and Affiliations
Corresponding author
Additional information
Neirofiziologiya/Neurophysiology, Vol. 37, Nos. 5/6, pp. 416–423, September–December, 2005.
Rights and permissions
About this article
Cite this article
Makii, E.A., Rodinskii, A.G. Suppression of abnormally increased excitability of monosynaptic spinal reflex arcs by riluzole. Neurophysiology 37, 365–371 (2005). https://doi.org/10.1007/s11062-006-0012-3
Received:
Issue Date:
DOI: https://doi.org/10.1007/s11062-006-0012-3