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.

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Traumatic spinal cord injury

Spinal cord injury (SCI) can lead to paraplegia or quadriplegia. Although there are no fully restorative treatments for SCI, various rehabilitative, cellular and molecular therapies have been tested in animal models. Many of these have reached, or are approaching, clinical trials. Here, we review these potential therapies, with an emphasis on the need for reproducible evidence of safety and efficacy. Individual therapies are unlikely to provide a panacea. Rather, we predict that combinations of strategies will lead to improvements in outcome after SCI. Basic scientific research should provide a rational basis for tailoring specific combinations of clinical therapies to different types of SCI.

/pdf/therapeutic-interventions-after-spinal-cord-injury-319za83fnv.pdf

Therapeutic interventions after spinal cord injury.

Role of pro-inflammatory cytokines released from microglia in neurodegenerative diseases.

Traumatic spinal cord injury (SCI) results not only in motor impairment but also in chronic central pain, which can be refractory to conventional treatment approaches. It has been shown recently that in models of peripheral nerve injury, spinal cord microglia can become activated and contribute to development of pain. Considering their role in pain after peripheral injury, and because microglia are known to become activated after SCI, we tested the hypothesis that activated microglia contribute to chronic pain after SCI. In this study, adult male Sprague Dawley rats underwent T9 spinal cord contusion injury. Four weeks after injury, when lumbar dorsal horn multireceptive neurons became hyperresponsive and when behavioral nociceptive thresholds were decreased to both mechanical and thermal stimuli, intrathecal infusions of the microglial inhibitor minocycline were initiated. Electrophysiological experiments showed that minocycline rapidly attenuated hyperresponsiveness of lumbar dorsal horn neurons. Behavioral data showed that minocycline restored nociceptive thresholds, at which time spinal microglial cells assumed a quiescent morphological phenotype. Levels of phosphorylated-p38 were decreased in SCI animals receiving minocycline. Cessation of delivery of minocycline resulted in an immediate return of pain-related phenomena. These results suggest an important role for activated microglia in the maintenance of chronic central below-level pain after SCI and support the newly emerging role of non-neuronal immune cells as a contributing factor in post-SCI pain.

https://www.jneurosci.org/content/jneuro/26/16/4308.full.pdf

Activated Microglia Contribute to the Maintenance of Chronic Pain after Spinal Cord Injury

The pathophysiology of acute spinal cord injury (SCI) involves primary and secondary mechanisms of injury. Though both mechanisms are involved in the neurological dysfunction in SCI most research however has focused on understanding the pathophysiology of the secondary damage and reducing the amount of delayed cell loss following SCI. Research has revealed extensive therapeutic windows in secondary injury mechanisms that could be manipulated by appropriate exogenous interventions. In contrast, primary injury to the cord happens unexpectedly, and it is associated with inevitable delays; ranging from several hours to days before care intervention is administered. Therefore, apart from achieving patient's stabilization, the therapeutic window in the primary phase of injury is essentially obliterated, and consequently inaccessible for specialized. Coupled to this, the exacerbating effect of secondary injury mechanisms has generally commenced before the specialist intervention. Hence, knowledge of secondary injury mechanisms and their intricacies are invaluable requisite for any tailored therapeutic strategy in the persistent search for a cure of SCI. There are about 25 well-established secondary injury mechanisms in SCI, and are found in bits or clusters in literature. A vast number of these articles are not open access. Besides, articles with a comprehensive catalog of these mechanisms are not readily available. This article has cataloged over twenty five identified secondary mechanisms of injury in the spinal cord in an open access portal, and is particularly versatile for starters in spinal cord injury research.

/pdf/secondary-injury-mechanisms-in-traumatic-spinal-cord-injury-2y31t0nave.pdf

Secondary injury mechanisms in traumatic spinal cord injury: a nugget of this multiply cascade

We examined the effects of minocycline, an anti-inflammatory drug, on functional recovery following spinal cord injury (SCI). Rats received a mild, weight-drop contusion injury to the spinal cord and were treated with the vehicle or minocycline at a dose of 90 mg/kg immediately after SCI and then twice at a dose of 45 mg/kg every 12 h. Injecting minocycline after SCI improved hind limb motor function as determined by the Basso-Beattie-Bresnahan (BBB) locomotor open field behavioral rating test. Twenty four to 38 days after SCI, BBB scores were significantly higher in minocycline-treated rats as compared with those in vehicle-treated rats. Morphological analysis showed that lesion size increased progressively in both vehicle-treated and minocycline-treated spinal cords. However, in response to treatment with minocycline, the lesion size was significantly reduced at 21–38 days after SCI when compared to the vehicle control. Minocycline treatment significantly reduced the number of terminal deoxynucleotidyl ...

Tae Y. Yune

Papers

Minocycline reduces cell death and improves functional recovery after traumatic spinal cord injury in the rat.