Spinal cord injury in the rat.
Only limited therapeutic measures are currently available for the treatment of spinal cord injury. This review describes the pathologic mechanisms of trauma-induced spinal cord injury in rats, which will contribute to new understanding of the pathologic process leading to spinal cord injury and to further development of new therapeutic strategies. Spinal cord injury induced by trauma is a consequence of an initial physical insult and a subsequent progressive injury process that involves various pathochemical events leading to tissue destruction; the latter process should therefore be a target of pharmacological treatment. Recently, activated neutrophils have been shown to be implicated in the latter process of the spinal cord injury in rats. Activated neutrophils damage the endothelial cells by releasing inflammatory mediators such as neutrophil elastase and oxygen free radicals. Adhesion of activated neutrophils to the endothelial cell could also play a role in endothelial cell injury. This endothelial cell injury could in turn induce microcirculatory disturbances leading to spinal cord ischemia. We have found that some therapeutic agents that inhibit neutrophil activation alleviate the motor disturbances observed in the rat model of spinal cord injury. Methylprednisolone (MPS) and GM1 ganglioside, which are the only two pharmacological agents currently clinically available for treatment of acute spinal cord injury, do not inhibit neutrophil activation in this rat model. Taken together, these observations raise a possibility that other pharmacological agents that inhibit neutrophil activation used in conjunction with MPS or GM1 ganglioside may have a synergistic effect in the treatment of traumatic spinal cord injury in humans.
Department of Laboratory Medicine, Kumamoto University School of Medicine, Japan.
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Y
Taoka
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Okajima
D000818:Animals; D004195:Disease Models, Animal; D005677:G(M1) Ganglioside / Q000627:therapeutic use; D005938:Glucocorticoids / Q000627:therapeutic use; D007962:Leukocytes / Q000502:physiology; D008775:Methylprednisolone / Q000627:therapeutic use; D051381:Rats; D013119:Spinal Cord Injuries / Q000473:pathology*
D005938:Glucocorticoids; D005677:G(M1) Ganglioside; D008775:Methylprednisolone