Traumatic spinal cord injury

Abstract

Traumatic spinal cord injury (SCI) has devastating consequences for the physical, social and vocational well-being of patients. The demographic of SCIs is shifting such that an increasing proportion of older individuals are being affected. Pathophysiologically, the initial mechanical trauma (the primary injury) permeabilizes neurons and glia and initiates a secondary injury cascade that leads to progressive cell death and spinal cord damage over the subsequent weeks. Over time, the lesion remodels and is composed of cystic cavitations and a glial scar, both of which potently inhibit regeneration. Several animal models and complementary behavioural tests of SCI have been developed to mimic this pathological process and form the basis for the development of preclinical and translational neuroprotective and neuroregenerative strategies. Diagnosis requires a thorough patient history, standardized neurological physical examination and radiographic imaging of the spinal cord. Following diagnosis, several interventions need to be rapidly applied, including haemodynamic monitoring in the intensive care unit, early surgical decompression, blood pressure augmentation and, potentially, the administration of methylprednisolone. Managing the complications of SCI, such as bowel and bladder dysfunction, the formation of pressure sores and infections, is key to address all facets of the patient's injury experience.

BRD4 inhibition attenuates inflammatory response in microglia and facilitates recovery after spinal cord injury in rats

“…[1][2][3] Primary injury, resulting from the extraneous mechanical force impacting directly on the spinal cord, is characterized by focal cellular, vascular and blood-spinal cord barrier injury; the primary injury of SCI is irreversible. [1][2][3] Primary injury, resulting from the extraneous mechanical force impacting directly on the spinal cord, is characterized by focal cellular, vascular and blood-spinal cord barrier injury; the primary injury of SCI is irreversible.…”

Level-Specific Differences in Systemic Expression of Pro- and Anti-Inflammatory Cytokines and Chemokines after Spinal Cord Injury

“…Traumatic spinal cord injury (SCI)—despite breakthroughs in pre-operative, surgical and post-operative care—continues to be a life-threatening injury, both acutely and chronically [1]. After primary mechanical injury, a dual-edged cascade of inflammatory and vascular events—collectively referred to as the secondary injury phase—ensues [2,3].…”

“…While it is difficult to determine the causative mechanism of secondary injury, several mechanisms including vascular disruption [4], glutamate excitoxicity [5,6], lipid peroxidation [7,8,9], blood-spinal-cord-barrier disruption [10,11,12] and ionic imbalance [13,14] have been the focus of therapeutic targeting. The ultimate consequence of these events is apoptosis, neuronal and axonal death, and de/dys-myelination manifesting as grey and white matter loss at the injury epicenter [1]. …”

Making Neurons from Human Stem Cells

“…The animal models have also allowed scientists to combine different treatments with stem cells to achieve the best possible outcomes [6]. Some of the problems that scientists are now working on include improving the survival of stem cells after transplantation and figuring out ways to encourage the transplanted cells to make connections with the patient's neurons [7].…”