Neuroprotective effects of riluzole: An electrophysiological and histological analysis in an in vitro model of ischemia

Abstract

The protective effects of riluzole against the neuronal damage caused by O2 and glucose deprivation (ischemia) was investigated in rat cortical slices by recording electrophysiologically the cortico-cortical field potential and by evaluating histologically the severity of neuronal death. Five minutes of ischemia determined an irreversible depression of the amplitude of the field potential. In addition, this insult caused a clear enhancement of the number of death cells that were specifically colored with trypan blue (a vital colorant which stains altered cells). We found that riluzole, which by itself depressed the synaptic transmission, neuroprotected when perfused 15-20 min before and during ischemia. In fact, due to the treatment with riluzole, the ischemia-induced irreversible depression of the field potential recovered and less cells were stained with trypan blue. These findings demonstrate that riluzole prevents neuronal death in an in vitro model of ischemia and suggest a therapeutic use of this drug in order to reduce the pathophysiological outcomes of stroke.

N‐ethyl lidocaine (QX‐314) protects striatal neurons against ischemia: An in vitro electrophysiological study

“…Several studies have suggested that sodium channel blockers have a neuroprotective role in ischemic brain conditions (Obrenovitch, 1998;Probert et al, 1997;Siniscalchi et al, 1998Siniscalchi et al, , 1999Smith and Meldrum, 1995;Taylor and Meldrum, 1995;Weber and Taylor, 1994;Wiard et al, 1995). It is believed that this protection mainly depends on the inhibition of voltage-sensitive sodium channels (Calabresi et al, 2003a,c;Meldrum, 1996;Siniscalchi et al, 1998Siniscalchi et al, , 1999. In agreement with previous data reporting a control of the ischemic membrane depolarization in medium spiny neurons in low-sodium conditions (Calabresi et al, 1999), we also observed a significant recovery of the amplitude of the striatal field potential following an ischemic episode with no additive protection exerted by QX-314.…”

“…In addition, we have observed that a more evident protection is obtained perfusing the slices with the strictly-related local anesthetic lidocaine. Several studies have suggested that sodium channel blockers have a neuroprotective role in ischemic brain conditions (Obrenovitch, 1998;Probert et al, 1997;Siniscalchi et al, 1998Siniscalchi et al, , 1999Smith and Meldrum, 1995;Taylor and Meldrum, 1995;Weber and Taylor, 1994;Wiard et al, 1995). It is believed that this protection mainly depends on the inhibition of voltage-sensitive sodium channels (Calabresi et al, 2003a,c;Meldrum, 1996;Siniscalchi et al, 1998Siniscalchi et al, , 1999.…”

Kainate‐induced currents in rat cortical neurons in culture are modulated by riluzole

“…Riluzole is also able to stimulate the large-conductance calcium-activated potassium channels in rat pituitary GH3 cells, to block in vitro the effects of NMDA and kainate in the rat striatum (Keita et al, 1997), and to exert neuroprotective properties in a model of ischemia (Siniscalchi et al, 1999). It has been also demonstrated that glutamatergic transmission pre-and postsynaptically is altered by riluzole (Cheramy et al, 1992;Hubert and Doble, 1989), although radioligand binding studies have not demonstrated that riluzole interacts directly with the glutamate receptors (Benavides et al, 1985;Debono et al, 1993;Koek and Woods, 1988).…”

Glutamate transporters in brain ischemia: to modulate or not?

“…In the MCAO model, a single dose of riluzole, injected up to 3 h after reperfusion, reduced the infarct volume 75% and improved neurological deficits [220] . Moreover, the in vitro model of ischemia, OGD, showed that small doses of riluzole prevented neuronal death [221] . N-acetylcysteine (NAC) is widely used as a mucolytic agent and in paracetamol intoxification.…”