Neurochemical Research

, Volume 44, Issue 1, pp 200–213 | Cite as

Mechanism of Neuroprotection Against Experimental Spinal Cord Injury by Riluzole or Methylprednisolone

  • Cynthia Sámano
  • Andrea NistriEmail author
Original Paper


Any spinal cord injury carries the potential for persistent disability affecting motor, sensory and autonomic functions. To prevent this outcome, it is highly desirable to block a chain of deleterious reactions developing in the spinal areas immediately around the primary lesion. Thus, early timing of pharmacological neuroprotection should be one major strategy whose impact may be first studied with preclinical models. Using a simple in vitro model of the rat spinal cord it is possible to mimic pathological processes like excitotoxicity that damages neurons because of excessive glutamate receptor activation due to injury, or hypoxic/dysmetabolic insult that preferentially affects glia following vascular dysfunction. While ongoing research is exploring the various components of pathways leading to cell death, current treatment principally relies on the off-label use of riluzole (RLZ) or methylprednisolone sodium succinate (MPSS). The mechanism of action of these drugs is diverse as RLZ targets mainly neurons and MPSS targets glia. Even when applied after a transient excitotoxic stimulus, RLZ can provide effective prevention of secondary excitotoxic damage to premotoneurons, although not to motoneurons that remain very vulnerable. This observation indicates persistent inability to express locomotor activity despite pharmacological treatment conferring some histological protection. MPSS can protect glia from dysmetabolic insult, yet it remains poorly effective to prevent neuronal death. In summary, it appears that these pharmacological agents can produce delayed protection for certain cell types only, and that their combined administration does not provide additional benefit. The search should continue for better, mechanism-based neuroprotective agents.


Excitotoxicity Metabolic perturbation Grey and white matter Glutamate Kainate Cell death 



Amyotrophic lateral sclerosis


Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid


American Spinal Injury Association


Arbitrary units


Anti-apoptotic regulator, and splicing isoform of bcl-x gene


Blood-cerebrospinal fluid barrier


Blood-leptomeningeal barrier


Blood-spinal barrier


CD200 ligand


CD200 receptor


Central nervous system


Central pattern generators


Spinal cord injury




Excitatory amino acid transporters


Cytokine erythropoietin


Food and Drug Administration


Glial fibrillary acidic protein


Glucocorticoid receptor


Hypoxic inducing factor 1α


Human central nervous system-derived neural stem cell








Lateral white matter


Mature myelin basic protein


Methylprednisolone sodium succinate


National Acute Spinal Cord Injury Study Trials


N-methyl-d-aspartic acid


Neuronal nitric oxide synthase




Pathological medium


Riluzole in Acute Spinal Cord Injury Study


Riluzole or rilutek


Reactive nitrogen species


Reactive oxygen species


Neurofilament H non-phosphorylated antibody


Superoxide dismutase


Activator transcription factor STAT




Tumor necrosis factor alpha


Transient receptor potential cation channel, subfamily M


Ventral white matter


White matter






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Authors and Affiliations

  1. 1.División de Ciencias Naturales e IngenieríaUniversidad Autónoma Metropolitana, Unidad CuajimalpaMexico CityMexico
  2. 2.Neuroscience DepartmentInternational School for Advanced Studies (SISSA)TriesteItaly

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