Acute Spinal Cord Injury, Part I: Pathophysiologic Mechanisms

Abstract

Spinal cord injury (SCI) is a devastating and common neurologic disorder that has profound influences on modern society from physical, psychosocial, and socioeconomic perspectives. Accordingly, the present decade has been labeled the Decade of the Spine to emphasize the importance of SCI and other spinal disorders. Spinal cord injury may be divided into both primary and secondary mechanisms of injury. The primary injury, in large part, determines a given patient's neurologic grade on admission and thereby is the strongest prognostic indicator. However, secondary mechanisms of injury can exacerbate damage and limit restorative processes, and hence, contribute to overall morbidity and mortality. A burgeoning body of evidence has facilitated our understanding of these secondary mechanisms of injury that are amenable to pharmacological interventions, unlike the primary injury itself. Secondary mechanisms of injury encompass an array of perturbances and include neurogenic shock, vascular insults such as hemorrhage and ischemia-reperfusion, excitotoxicity, calcium-mediated secondary injury and fluid-electrolyte disturbances, immunologic injury, apoptosis, disturbances in mitochondrion function, and other miscellaneous processes. Comprehension of secondary mechanisms of injury serves as a basis for the development and application of targeted pharmacological strategies to confer neuroprotection and restoration while mitigating ongoing neural injury. The first article in this series will comprehensively review the pathophysiology of SCI while emphasizing those mechanisms for which pharmacologic therapy has been developed, and the second article reviews the pharmacologic interventions for SCI.

Oxidative stress and antioxidative parameters in patients with spinal cord injury: implications in the pathogenesis of disease

“…However, free radicals have an important role in the pathogenesis of SCI. 7 There is little information about oxidative stress in SCI. Moreover, there are several disorders associated with oxidative stress that are manifested by LP, protein oxidation and other markers.…”

Asiatic acid, a pentacyclic triterpene in Centella asiatica, attenuates glutamate-induced cognitive deficits in mice and apoptosis in SH-SY5Y cells

“…Glutamate (Glu)-induced excitotoxicity plays an important role in the pathogenesis of these diseases [2,3] . Glu-induced neuronal death is initiated by overstimulation of N-methyl-D-aspartate (NMDA) receptors, resulting in an increase in intracellular free calcium, followed by the activation of catabolic enzymes and leading to an intracellular cascade of cytotoxic events.…”

Quantitative assessment of spinal cord perfusion by using contrast-enhanced ultrasound in a porcine model with acute spinal cord contusion

“…One possible explanation was that the initial impact disrupted the blood supplies within the spinal cord and resulted in local infarction caused by hypoxia and ischemia. 22 Moreover, hypoperfusion frequently indicated vascular damage from immediate vasospasm of superficial vessels to intraparenchymal hemorrhage and the formation of thromboses. 21,23 Hyperperfusion in pericontusion area were ascribed to an increasing volume of blood flow, dilation of microvessels, loss of autoregulation or opening of an arteriovenous shunt.…”