Advances in Secondary Spinal Cord Injury

Abstract

The outcome of spinal cord injury depends on the extent of secondary damage produced by a series of cellular and molecular events initiated by the primary trauma. This article reviews the evidence that secondary spinal cord injury involves the apoptotic as well as necrotic death of neurons and glial cells. Also discussed are the major factors that can contribute to cell death, such as glutamatergic excitotoxicity, free radical damage, cytokines, and inflammation. The development of innovative therapeutic strategies to reduce secondary spinal cord injury depends on an increased understanding of secondary injury mechanisms at the molecular and biochemical level. Such therapeutic interventions may include the use of antiapoptotic drugs, free radical scavengers, and anti-inflammatory agents. These could be targeted to block key reactions on cellular and molecular injury cascades, thus reducing secondary tissue damage, minimizing side effects, and improving functional recovery.

Calpain inhibitor AK 295 inhibits calpain-induced apoptosis and improves neurologic function after traumatic spinal cord injury in rats

“…Secondary damage has been shown to induce the excessive release of excitatory amino acids and to cause intracellular calcium overload, the induction of free-radical-induced lipid peroxidation, and apoptosis (programmed cell death) 24,47 . Apoptosis is an actively regulated response that occurs after various cells have been subjected to external or internal stimuli.…”

“…Apoptosis is an actively regulated response that occurs after various cells have been subjected to external or internal stimuli. Recent experimental studies and clinical observations have revealed that spinal cord lesions are greatly exacerbated by apo ptosis 10,12,13,15,18,19,[22][23][24] . However, the molecular and cellular mechanism of apoptosis is still not fully understood.…”

“…Both caspases and calpains are members of a group of proteases; the former is a calcium-independent protease, and the latter is a calcium-dependent protease. Laboratory findings and clinical evidence have suggested that caspases and calpains have an important role in the progression of programmed cell death and that multiple molecular pathways can lead independently to that type of cell death 15,[22][23][24]32 The activation of 1 protease can lead to the cleavage and activation of additional enzymes of the same or other proteases, and an amplified protease cascade results 46 .…”

Secondary degeneration reduced by inosine after spinal cord injury in rats

“…[1][2][3][4] Secondary degeneration is one of the main pathological events following spinal cord injury (SCI). Attenuation of secondary degeneration has been considered critical to the outcome of the patients of SCI.…”

“…Attenuation of secondary degeneration has been considered critical to the outcome of the patients of SCI. Although various pharmacological strategies, such as administrations of protein synthesis inhibitors, free radical scavengers, gangliosides and NMDA receptor antagonists, [3][4][5][6] have been developed to reduce secondary injury, only high-dose systemic administration of methylprednisolone within 8 h after injury is proved clinically useful for human SCI. [7][8][9] However, the use of methylprednisolone is effective only within a relatively narrow time window of 8 h after SCI, which is often impossible in many places around the world.…”