Table 10.

Riluzole

Paper	Animal model and injury model	Intervention and timing	Experimental groups	Reported outcomes: • Histologic/biochemical/physiological • Behavioral
Kitzman Neurosci Lett2009	Model: Female Adult SD Rats, 200–250g Injury: S2 Cord Transection (through L1/2 laminectomy)	Riluzole IP • 8 mg/kg @ 4w PI, then q24h × 3 days • 10 mg/kg @ 4w PI, then q24h × 3 days	SCI + • Riluzole 8 mg/kg • Saline controls for 8 mg/kg • Riluzole 10 mg/kg • Saline controls for 10 mg/kg n∼4-5 per group	Histologic/Biochemical/Physiological: Not reported. Behavioral: At 1h and 3h post-administration, but not later, 8 mg/kg riluzole significantly decreased the responsiveness of the tail musculature to a pinch and light stimuli (representative of decreased spasticity). The drug at 8 mg/kg did not produce any overt indications of locomotor ataxia or lethargy in SCI animals. Riluzole at 10 mg/kg significantly decreased the responsiveness of the tail to a pinch, stretch and light stimuli. However, this dose produced indications of lethargy and locomotor ataxia in approximately 67% of the SCI animals tested.
Ates J Clin Neurosci2007	Model: Adult Male Wistar albino Rats, 200–250g Injury: T7/T10 Weight Drop Contusion 5g × 10 cm	Riluzole IP • 8 mg/kg @ 0h PI Mexiletine IP • 80 mg/kg @ 0h PI Phenytoin IP • 200 mg/kg @ 0h PI	SCI + • Riluzole • Mexiletine • Phenytoin • Saline 1 ml Sham n = 18/group	Histologic/Biochemical/Physiological: All 3 drug treatment groups showed greater myelin and neuronal gray matter sparing and smaller lesion areas, MDA levels, and spinal cord water content than controls. However, MDA and water levels in the phenytoin-treated group were higher than the other 2 drug groups. Behavioral: Sodium channel blockers resulted in improved motor function scores and inclined plane angles. However, phenytoin-treated rats revealed significantly lower improvement rates than mexiletine and riluzole-treated rats for the inclined plane.
McAdoo Brain Res2005	Model: Male SD Rats, 240–320g Injury: • T9/T10 MASCIS Impactor 25 mm × 10 g • Infinite Horizons 150 kdyn	Sodium channel blockers Riluzole via Fibre • 2 mM @ 0h PI Mexiletine IP • 80 mg/kg @ 0h PI QX-314 • 1.5 μl of a 2.0 mM solution @ 0h PI NMDA receptor blockers Memantine MK-801 AMPA/kainate receptor blockers Cyclothiazide NBQX GYK 52466	SCI + • Riluzole • Mexilentine • QX-314 • MK-801 • Memantine • Cyclothiazide • NBQX • GYK 52466 • ACSF control n = 6/group	Histologic/Biochemical/Physiological: The effect of the sodium channel blockade on trauma-induced glutamate release was determined using microdialysis. Sodium channel blockade did not decrease glutamate release within the injured spinal cord. Infact, none of the agents tested had an appreciable effect on glutamate release following SCI. Behavioral: Not reported.
Schwartz J Neurosurg2001	Model: Female Adult Wistar Rats; 225-280g Injury: C7/T1 Extradural Clip Compression 53g	Sodium channel blockers Riluzole IP • 5 mg/kg @ 0h PI CNS5546A IP • 15 mg/kg @ 0h PI Phenytoin IP@ 0h PI • 30 mg/kg 2HpβCD Vehicle • 5 mg/kg @ 0h PI	SCI + • Riluzole • CNS5546A • Phenytoin • Vehicle n = 15/group	Histologic/Biochemical/Physiological: Riluzole treated rats consistently yielded more FG-positive retrograde labeled neurons in the brain stem than controls, with significantly more neurons counted within the red nucleus. The other sodium channel blockers did not improve the integrity of descending axons. LFB and H&E stained transverse spinal cord sections demonstrated that all drugs were able to significantly reduce cavitation, with riluzole treatment offering the greatest protection. Behavioral: Only riluzole was able to improve BBB scores above controls. All sodium channel blockers resulted in greater inclined plane angles; however significance was only reached with riluzole.
Mu Brain Res2000 a	Model: Female Long-Evans Rats, 225-250g Injury: T10 NYU Impactor 12.5 mm Drop (mean value for cord compression was 1.66 ± 0.11)	Riluzole IP • 8 mg/kg @ 15min and 2h PI Methylprednisolone (MP) IV • 30 mg/kg @15min and 2h PI	SCI + • Riluzole • Riluzole + MP • MP • Vehicle n = 9/group	Histologic/Biochemical/Physiological: At 4h PI, spinal cords were removed and synaptosomes prepared and examined using five measures of oxidative stress: 1) mitochondrial function; 2) reactive oxygen species levels; 3) thiobarbituric acid reactive product levels; 4) glutamate and 5) glucose levels. Riluzole and MP treatments improved mitochondrial function and enhanced glutamate and glucose uptake. MP treatment also reduced lipid peroxidation. MP, alone or in combination with riluzole, reduced malondialdehyde levels. The combination treatment was effective in improving all five measures of oxidative stress. Behavioral: Not reported.
Mu J Neurotrauma2000 b	Model: Female Long-Evans Rats, 225-250g Injury: T10 SCI Impactor rod 12.5 mm drop	Riluzole IP • 8 mg/kg @ 2h and 4h PI and then daily × 1 week Methylprednisolone (MP) IV via the femoral vein • 30 mg/kg @ 2h and 4h PI	SCI + • Riluzole • Riluzole + MP • MP • Vehicle n = 9/group	Histologic/Biochemical/Physiological: The overall appearance of spinal cord cavitation for transverse sections was similar for vehicle controls, Rriluzole and MP. However, the combination of Rriluzole + MP yielded significantly increased spared tissue. Behavioral: Riluzole or MP alone was not able to improve BBB scores above vehicle controls. At 4, 5 and 6w post-SCI the combination of riluzole + MP yielded significantly improved BBB scores (vehicle = 9.7 & 10.5; riluzole + MP = 12.5 & 13.7 at 5 and 6w, respectively).
Springer J Neurochem1997	Model: Rats; (No further details of animals used) Injury: T10 NYU Impactor 25 mm Drop	Riluzole IP • 8 mg/kg @ 15min PRIOR to and 2h PI	SCI + • Riluzole • Saline n = 42/group	Histologic/Biochemical/Physiological: Immunocytochemical and Western Blot approaches were used to determine the ability of riluzole to attenuate microtubule-associated protein (MAP2) loss post-SCI. Riluzole treatment was associated with significant ability to reduce the loss of MAP2 at 24 h post-SCI. Behavioral: Not reported.
Stutzmann NeuroReport1996	Model: Male Wistar Rats (280 ± 20g) Injury: T10/T12 Compresison via Fogarty balloon catheter 2.5 bars × 8 min	Riluzole IV • 2 mg/kg @ 30min PI, then twice daily × 10d Vehicle (1.5% pluronic F68 in 0.9% NaCl @ 30min PI, then twice daily × 10d	SCI + • Riluzole • Vehicle n = 10/group	Histologic/Biochemical/Physiological: Vehicle-treated controls showed hemorrhage within the sub-dural space and necrosis of the grey and white matter. This damage was attenuated with riluzole treatment, especially in the white matter. Control somatosensory evoked potentials (SSEPs) recorded in all rats prior to SCI were abolished following injury. Vehicle treated rats did not recover SSEPs, however riluzole treatment led to significant recovery of SSEP amplitude, duration and latency. Behavioral: Riluzole treatment improved behavioral recovery. Qualitatively the riluzole-treated rats were able to use their paws to sit upright. Vehicle-treated controls could not sit upright.

T8: thoracic vertebra 8; C5: cervical vertebra 5; IP: intraperitoneal; IV: intravenous; SC: subcutaneous;

AMPA: α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate; BBB: Basso, Beattie and Bresnahan locomotor test; FG: fluorogold; LFB: Luxol Fast Blue; MDA: malondialdehyde; MP: Methylprednisolone; NMDA: N-methyl D-aspartate; SD rats: Sprague-Dawley rats.