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Damage to the spinal cord can result in irreversible impairments or complete loss of motor, sensory and autonomic functions.
Riluzole and magnesium have been widely investigated as neuroprotective agents in animal models of spinal cord injury. As
these drugs protect the injured spinal cord through different mechanisms we aimed to investigate if their neuroprotective efficacy
could be cumulative. An in vivo experiment was set using female Wistar Han rats that underwent a thoracic spinal cord contusion
(T8) using a weight drop method. An hour after injury, animals received: Saline, riluzole (2.50 mg/kg), magnesium chloride (24.18
mg/kg) in a polyethylene glycol formulation or a combined treatment (riluzole and magnesium). Subsequent treatments were given
in four intraperitoneal injections (spaced 12 hours apart). The Basso, Beattie and Bresnahan Locomotor Rating Scale, an activity box
test and a swimming test were used to evaluate behavioral recovery over a four-week period. Histological analysis of the spinal cords
was performed to measure the extent and volume of the lesion, axonal preservation, serotonergic and glutamatergic fiber sparing,
motor neuron survival and inflammation. Our results show that only the riluzole treatment significantly improved behavioral
recovery (9.1�±1.2) when compared to saline controls (6.2�±1.8). Riluzole also promoted tissue sparing and reduced lesion volume
with animals presenting a significantly smaller lesion (3.23�±0.26 vs. 4.74�±0.80 mm2). Riluzole treatment also induced significant
axonal preservation, as well as serotonergic fiber sparing. In conclusion, our results suggest that the combined treatment, although
simultaneously targeting two excitotoxic-related mechanisms, did not further improve behavioral and histological outcome, when
compared with riluzole given alone.