This review provides a concise outline of the advances made in the care of patients and to the quality of life after a traumatic spinal cord injury (SCI) over the last century. Despite these improvements reversal of the neurological injury is not yet possible. Instead, current treatment is limited to providing symptomatic relief, avoiding secondary insults and preventing additional sequelae. However, with an ever-advancing technology and deeper understanding of the damaged spinal cord, this appears increasingly conceivable. A brief synopsis of the most prominent challenges facing both clinicians and research scientists in developing functional treatments for a progressively complex injury are presented. Moreover, the multiple mechanisms by which damage propagates many months after the original injury requires a multifaceted approach to ameliorate the human spinal cord. We discuss potential methods to protect the spinal cord from damage, and to manipulate the inherent inhibition of the spinal cord to regeneration and repair. Although acute and chronic SCI share common final pathways resulting in cell death and neurological deficits, the underlying putative mechanisms of chronic SCI and the treatments are not covered in this review.

AO Spine Reference Centre & Institute of Health & Biomedical Innovation, Queensland University of Technology, Brisbane, Australia. Traumatic spinal cord injury (SCI) is a devastating condition with no curative therapy. Pro-inflammatory therapy has been suggested recently to try and reduce the inhibitory glial scar and promote neural regeneration and healing. The aim of this study is to investigate the potential of sustained delivery of angiogenic/pro-inflammatory growth factors to reduce the secondary degeneration after spinal cord injury. Adult male Wistar Kyoto rats (200-300g; 12-16weeks old) were subjected to cord hemisections via a T10 laminectomy. Animals were randomised to treatment or control groups after the spinal cord injury had been induced. Treatment consisted of implantation of a mini-osmotic pump capable of delivering 5 micrograms vascular endothelial growth factor (VEGF) and 5 micrograms platelet-derived growth factor (PDGF), via a catheter, to the site of the lesion, over 7 days(n=6). Control animals were subjected to either cord lesion only (n=6) or lesion plus mini-pump delivering PBS (phosphate-buffered saline) solution (n=6). Rats were sacrificed at one month and the spinal cords were harvested and examined by immunohistology, using anti-neurofilament-200 and anti-Glial Acidic Fibrillary Acidic Protein (GFAP) antibodies. RESULTS: Active treatment spinal cords showed a higher level with aboration of the axonal filament through the defect and more dense neurofilament-200 staining at the lesion site compared to both control groups. The treatment also showed the elevated presence of activated microglia in the lesion, whilst distal to the lesion the microglia and astrocytes retained an unreactive phenotype. Pro-inflammatory therapy in the rat spinal cord-injury model showed favourable histological findings after sustained delivery of PDGF and VEGF

Introduction: Acute neurological damage from spinal cord injuries is believed to be localised, however it initiates a cascade of secondary events which usually leads to extensive and permanent neurological deficit. The secondary damage begins with the disruption of the blood-spinal cord barrier which unleashes a protracted inflammatory response. This prolonged inflammatory response is the catalyst for the secondary neurodegeneration and limited repair response that occurs in the chronic phase of a spinal cord injury. In this study it was proposed that the acute delivery of the angiogenic growth factors vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) would mediate inflammation and restore the blood spinal cord barrier. This would minimise the formation of glial scar and reduce the extent of secondary degeneration caudal and cranial to the lesion site. Methods: Adult male Wistar rats (400g) were anesthetised. Complete laminectomies were performed at T10 and the animals were subjected to T10 hemisection. Animals were randomised to a treatment group (Lesion Control (LC), Gel Control (GC) and Angiogenic Gel (AG)) after the spinal cord was cut. Each treatment group had 6 animals sacrificed 3 months post injury. Sections were stained with antibodies to neurofilament 200, glial fibrillary acidic protein, smooth muscle actin (SMA), and fluorescent secondary antibodies and mounted with DAPI. The lesion size was measured from horizontal histological sections of the midline from 5 animals in each group using Axiovision version 4.6.1.0 (Carl Zeiss Imaging Solutions, Germany). Results: The mean lesion size for the lesion control group was 2.09mm2, 1.97mm2 for the gel control group and 0.45mm2 for the active gel group. A t-test was used to confirm that the differences between the active gel and the two control groups were statistically significant (AG vs LC p= 0.021 AG vs GC p= 0.026). Histology showed a marked improvement of the morphology of the astrocytes in the treatment group over the control groups indicating that the treatment affected the population of reactive astrocytes. SMA staining showed an increased level of revascularisation in the treated lesions. Discussion: Spinal cords do not heal because of prolonged inflammation which leads to secondary necrotic events, scar formation and the inhibition of regeneration. In this study we present a method for regulating the post lesion inflammatory signals, significantly reducing post-lesion scar formation. We propose the delivery of VEGF/PDGF significantly increases the permeability of the blood spinal cord barrier to neutrophils and macrophages and promotes angiogenesis observed in the lesion site. This may have two major effects on the progression of the spinal cord injury. Firstly, by increasing the initial influx of inflammatory cells it enables the faster removal of damaged tissue and phagocytosis of apoptotic cells thereby restoring the balance in favour of regulated inflammation and results in a finite and reduced inflammation time. Secondly, combination of VEGF and PDGF provides a robust angiogenic response and reduces ischemia, the population of reactive astrocytes and the capacity to form glial scars. These growth factors appear to moderate the secondary degenerative changes that result from the prolonged inflammation and thus promote the inherent capacity for regeneration

The subject of central nervous system damage includes a wide variety of problems, from the slow selective ‘picking off’ of characteristic sub-populations of neurons typical of neurodegenerative diseases, to the wholesale destruction of areas of brain and spinal cord seen in traumatic injury and stroke. Experimental repair strategies are diverse and the type of pathology dictates which approach will be appropriate. Damage may be to grey matter (loss of neurons), white matter (cutting of axons, leaving neurons otherwise intact, at least initially) or both. This review will consider four possible forms of treatment for repair of the human central nervous system.