Current status of acute spinal cord injury pathophysiology and emerging therapies: promise on the horizon

Abstract

<jats:p>This review summarizes the current understanding of spinal cord injury pathophysiology and discusses important emerging regenerative approaches that have been translated into clinical trials or have a strong potential to do so. The pathophysiology of spinal cord injury involves a primary mechanical injury that directly disrupts axons, blood vessels, and cell membranes. This primary mechanical injury is followed by a secondary injury phase involving vascular dysfunction, edema, ischemia, excitotoxicity, electrolyte shifts, free radical production, inflammation, and delayed apoptotic cell death. Following injury, the mammalian central nervous system fails to adequately regenerate due to intrinsic inhibitory factors expressed on central myelin and the extracellular matrix of the posttraumatic gliotic scar. Regenerative approaches to block inhibitory signals including Nogo and the Rho-Rho–associated kinase pathways have shown promise and are in early stages of clinical evaluation. Cell-based strategies including using neural stem cells to remyelinate spared axons are an attractive emerging approach.</jats:p>

Targeting Mitochondrial Function for the Treatment of Acute Spinal Cord Injury

“…Detailed discussion of these changes is beyond the scope of this review, and the reader is directed to several excellent reviews on the pathophysiological changes occurring in the spinal cord following injury [6][7][8][9]. However, of particular interest for this discussion are the ionic shifts that occur in the injured tissue that persist for hours and days following SCI [10][11][12][13].…”

Perspectivas da aplicação das conotoxinas bloqueadoras de canais para cálcio dependentes de voltagem no trauma medular

“…A quebra da barreira hematoespinal desencadeia aumento da permeabilidade vascular, com formação de edema, início da resposta infl amatória, perda de cargas aniônicas e extravasamento de proteínas plasmáticas (ROWLAND et al, 2008). Concomitantemente, a ruptura da microvasculatura gera hemorragia que, associada ao edema, leva à isquemia medular, estendendo-se rostral e caudalmente (HULSEBOSCH, 2002;ROWLAND et al, 2008).…”

Emerging Approaches to the Surgical Management of Acute Traumatic Spinal Cord Injury

“…Numerous acute therapies for SCI have appeared promising at the preclinical stages of study; however, most of these have failed to translate into clinically effective treatments [6]. From a pharmaceutical standpoint, all of the drug therapies tested in clinical efficacy trials have failed to demonstrate substantive benefit, with only high-dose methylprednisolone succinate showing modest success in the landmark National Acute Spinal Cord Injury Study (NASCIS)-2 trial [7].…”