Aims. The involvement of cyclin D1 in the proliferation of
Spinal cord injury (SCI) is a devastating disorder for which the identification of exacerbating factors is urgently needed. Although age, blood pressure and infection are each considered to be prognostic factors in patients with SCI, exacerbating factors that are amenable to treatment remain to be elucidated. Microglial cells, the resident immune cell in the CNS, form the first line of defense after being stimulated by exposure to invading pathogens or tissue injury. Immediately after SCI, activated
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
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.
Introduction Approximately one quarter of spinal cord injury patients will develop post-traumatic syringomyelia. This condition can produce devastating neurological deficits, and treatment is often not successful. The pathogenesis is unknown, however it is likely that initial cyst formation plays an important role in subsequent syrinx development. An up-regulated inflammatory process observed following contusive and transective spinal cord injury has been proposed as a contributory factor in secondary spinal cord damage. Specifically, a depletion or suppression of macrophages following injury is shown to preserve neurons and myelinated axons. This study examines the role of inflammation following excitotoxic spinal cord injury, a potent precursor to syrinx formation. Methods Twenty-four male Sprague-Dawley rats were divided into six groups. Twenty rats received four 0.5 μL injections of 24 mg/ mL quisqualic acid and 1% Evans blue from the rostral C8 to the caudal T1 level. Ten microlitres of 250 mg/ mL kaolin were then injected into the subarachnoid space. Animals were sacrificed at 1, 5, 10, 20 or 50 days following the injections. There were four normal control animals. Spinal cord tissue was frozen and sectioned, and cytoplasmic antigen ED1 was detected immunohistochemically with anti-ED1 antibody. This antibody is specific to phagocytic macrophages and reactive
Introduction: Apoptosis, or secondary cell death, has been demonstrated in a number of neurological conditions, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and brain ischaemia. It is well established from studies of acute spinal cord injury that apoptosis seems an important factor in secondary cell death and irreversible neurological deficit. It is only recently that studies have emerged analysing secondary cell death in chronic injury to the cord. In this study, the spatial and temporal expression of apoptotic cells was analysed in acute traumatic spinal cord injury (SCI) (n=6) and chronic myelopathies due to metastatic tumour (n=5), degenerative spondylosis (n=6) and syringomyelia (n=4). The study aimed to demonstrate apoptosis in compressive spinal cord injury and to analyse the spatial and temporal distribution of apoptosis in acute and chronic myelopathy. Method: Archival material from 21 spinal cords of patients with documented myelopathy during life and definitive evidence on post mortem examination were available for study. The spatial and temporal expression of apoptotic cells was analysed in acute traumatic spinal cord injury (SCI) (n=6) and chronic myelopathy due to metastatic tumour (n=5), degenerative spondylosis (n=6) and syringomyelia (n=4). Immunohistochemical analysis of each specimen was conducted using markers of apoptosis, as well as the biochemical apoptotic marker TUNEL. A total of 1800 histopathological slides were analysed. Specimens were also analysed using confocal microscopy to identify the immunopositive cell type. A combination of morphological, immunohistochemical and in situ end-labelling techniques were used to investigate the mechanism of cell death in this experiment. The analytical techniques employed were aimed at showing firstly the presence of apoptosis and secondly the size and position of the damaged regions. Results: Positivity for active Caspase-3, DNA-PKCS, PARP, TUNEL and active Caspase-9 was found in glia (oligodendrocytes and microglia) axons and neurons in both acute and chronic compression above, below and at the site of compression. In chronic compression, the severity of positivity for apoptotic immunological markers was positively correlated with the severity of white matter damage, as measured by APP immunostaining for axonal injury, and Wallerian degeneration. There was no correlation between the duration of chronic compression and immunopositivity for apoptotic markers. In acute SCI, axonal swellings were consistently positive for Caspases −9 and -3, suggesting mitochondrial activation of apoptotic pathways. Conclusion: Apoptosis occurs in both acute and chronic spinal cord injury. In acute compression, axonal injury is associated with apoptotic immunopositivity of glia and neurons. In chronic compression, apoptosis of oligodendrocytes and
INTRODUCTION: Apoptosis, or secondary cell death, has been demonstrated in a number of neurological conditions, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and brain ischaemia. It is well established from studies of acute spinal cord injury that apoptosis seems an important factor in secondary cell death and irreversible neurological deficit. It is only recently that studies have emerged analysing secondary cell death in chronic injury to the cord. In this study, the spatial and temporal expression of apoptotic cells was analysed in acute traumatic spinal cord injury (SCI) (n=6) and chronic myelopathies due to meta-static tumour (n=5), degenerative spondylosis (n=6) and syringomyelia (n=4). The study aimed to demonstrate apoptosis in compressive spinal cord injury and to analyse the spatial and temporal distribution of apoptosis in acute and chronic myelopathy. METHOD: Archival material from 21 spinal cords of patients with documented myelopathy during life and definitive evidence on post mortem examination were available for study. The spatial and temporal expression of apoptotic cells was analysed in acute traumatic spinal cord injury (SCI) (n=6) and chronic myelopathy due to metastatic tumour (n=5), degenerative spondylosis (n=6) and syringomyelia (n=4). Immunohistochemical analysis of each specimen was conducted using markers of apoptosis, as well as the biochemical apoptotic marker TUNEL. A total of 1800 histopathological slides were analysed. Specimens were also analysed using confocal microscopy to identify the immunopositive cell type. A combination of morphological, immunohistochemical and in situ end-labelling techniques were used to investigate the mechanism of cell death in this experiment. The analytical techniques employed were aimed at showing firstly the presence of apoptosis and secondly the size and position of the damaged regions. RESULTS: Positivity for active Caspase-3, DNA-PKCS, PARP, TUNEL and active Caspase-9 was found in glia (oligodendrocytes and microglia) axons and neurons in both acute and chronic compression above, below and at the site of compression. In chronic compression, the severity of positivity for apoptotic immunological markers was positively correlated with the severity of white matter damage, as measured by APP immunostaining for axonal injury, and Wallerian degeneration. There was no correlation between the duration of chronic compression and immunopositivity for apoptotic markers. In acute SCI, axonal swellings were consistently positive for Caspases −9 and -3, suggesting mitochon-drial activation of apoptotic pathways. CONCLUSION: Apoptosis occurs in both acute and chronic spinal cord injury. In acute compression, axonal injury is associated with apoptotic immunopositivity of glia and neurons. In chronic compression, apoptosis of oligodendrocytes and
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.
