Journal of neurotrauma
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Journal of neurotrauma · Nov 2007
Social and environmental enrichment improves sensory and motor recovery after severe contusive spinal cord injury in the rat.
Neuropathic pain and motor dysfunction are difficult problems following spinal cord injury (SCI). Social and environmental enrichment (SEE), which models much of the clinical rehabilitation environment for post-SCI persons, is the focus of the current investigation which examines the effects of multiple-housing and the addition of climbing spaces, improved bedding and crawl toys on the sensory and motor recovery following a severe contusive SCI. Efficacy was determined with sensory testing, open-field motor behavioral testing, lesion volume analysis and quantification of brain-derived neurotrophic factor (BDNF) in the lumbar spinal cord with and without SEE provided during the recovery period. ⋯ SEE significantly increased the total volume of a thoracic segment of cord encompassing the injury site at 12 weeks, by reducing cavitation and increasing both the volume of grey and white matter spared, compared to SCI alone. When BDNF levels were examined in the injured lumbar spinal cord, SEE significantly returned BDNF levels to near-normal. These data suggest that immediate use of SEE after contusive SCI is able to improve overall spinal cell survival and prevent much of the sensory and motor dysfunction that accompanies contusive SCI.
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Journal of neurotrauma · Nov 2007
Chondroitin sulfate proteoglycans in spinal cord contusion injury and the effects of chondroitinase treatment.
Chondroitinase treatment of experimental spinal cord injury improves recovery of sensory, motor, and autonomic functions. Chondroitinase catalyzes the cleavage of glycosaminoglycans (GAGs) from the core proteins of chondroitin sulfate proteoglycans (CSPGs). Little is known about changes in production of these proteoglycans in the clinically relevant contusion model of spinal cord injury or if CSPG content is altered by chondroitinase treatment. ⋯ Chondroitinase treatment had little impact upon the CPSG protein content. Changes in message levels of these CSPGs are also reported. This demonstrates that expression patterns of CSPGs in contusion injury are similar to those surrounding surgical hemisection lesions and demonstrates that the sensory and motor function enhancing effects of chondroitinase are likely due to removal of GAG chains rather than reduction in CSPG content.
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Journal of neurotrauma · Oct 2007
Effect of penetrating brain injury on aquaporin-4 expression using a rat model.
Cerebral edema (CE) is a frequent and potentially lethal consequence of various neurotraumas, including penetrating brain injury (PBI). Aquaporin-4 (AQP4) water channel is predominantly expressed by astrocytes and plays an important role in regulating water balance in the normal and injured brain. Using a rat model of PBI, we show that AQP4 immunoreactivity was substantially increased in the peri-injury area at both 24 and 72 h after PBI. ⋯ Western analysis confirmed the increase in AQP4 immunoreactivity observed in the injured tissue. The apparent increase in AQP4 immunoreactivity was likely due to de novo AQP4 protein synthesis, as most of the increased AQP4 immunoreactivity was found in the soluble (cytosolic) fraction. Our results demonstrate dynamic spatial and temporal changes in AQP4 expression that contribute to the molecular pathophysiology of PBI.
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Journal of neurotrauma · Oct 2007
Diffusion-weighted magnetic resonance imaging improves outcome prediction in adult traumatic brain injury.
In patients with traumatic brain injury (TBI), diffuse axonal injury (DAI) accounts for a significant amount of parenchymal injury. Diffusion weighted magnetic resonance imaging (DWI) is known to be sensitive for detecting visible DAI lesions. We focused on detection of non-visible, quantifiable diffusion changes in specific normal-appearing brain regions, using apparent diffusion coefficient (ADC) maps. ⋯ Patients with more severe injury (i.e., GCS 3-8) had significantly different mean ADC values than control patients (p
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Journal of neurotrauma · Oct 2007
Post-treatment with the cyclosporin derivative, NIM811, reduced indices of cell death and increased the volume of spared tissue in the acute period following spinal cord contusion.
Cyclosporin A (CsA) is a potent immunosuppressive drug shown to inhibit mitochondrial permeability transition (mPT). Although the therapeutic efficacy of CsA in traumatic brain injury is being investigated, CsA is highly neurotoxic and any neuroprotective effect in models of spinal cord injury (SCI) is unclear. NIM811 is a non-immunosuppressive CsA derivative that inhibits mPT, and is significantly less cytotoxic than CsA. ⋯ NIM811 also reduced the volume of the lesion, and enhanced the volumes of spared gray and white matter at 7 days post-injury. Together, these findings suggest that NIM811 treatment promoted tissue survival following SCI, in part, through inhibition of apoptotic mechanisms. This is the first study to demonstrate the therapeutic potential of NIM811 post-treatment in a model of acute SCI, and supports the need for continued investigation into NIM811 as a neuroprotective treatment for human SCI.