Journal of neurotrauma
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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
Diffuse brain injury in the immature rat: evidence for an age-at-injury effect on cognitive function and histopathologic damage.
Diffuse axonal injury is a significant component of the pathology of moderate-severe pediatric traumatic brain injury in children less than 4 years of age, and is associated with poor cognitive outcome. However, cognitive deficits or gross histopathologic abnormalities are typically not observed following moderate-severe diffuse brain injury in the immature (17-day-old) rat. In order to test whether the age of the immature animal may influence post-traumatic outcome, non-contusive brain trauma was induced in post-natal day (PND) 11 or 17 rats. ⋯ Quantitative analysis revealed a time-dependent increase in tissue loss in the injured hemisphere (7-10%) in the younger animals, and a modest extent of tissue loss in the older animals (3-4%). Traumatic axonal injury was observed to similar extents in the white matter and thalamus below the impact site in both brain-injured PND11 and 17 rats. These data demonstrate that non-contusive (diffuse) brain injury of moderate severity in the immature rat is associated with chronic cognitive deficits and long-term histopathologic alterations and suggest that the age-at-injury is an important parameter of behavioral and pathologic outcome following closed head injury in the immature age group.
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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.
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Journal of neurotrauma · Oct 2007
Inflammation in human brain injury: intracerebral concentrations of IL-1alpha, IL-1beta, and their endogenous inhibitor IL-1ra.
Following traumatic brain injury (TBI), cascades of inflammatory processes occur. Laboratory studies implicate the cytokines interleukin-1alpha (IL-1alpha) and IL-1beta in the pathophysiology of TBI and cerebral ischemia, whilst exogenous and endogenous interleukin-1 receptor antagonist (IL-1ra) is neuroprotective. We analyzed IL-1alpha, IL-1beta, and IL-1ra in brain microdialysates (100-kDa membrane) in 15 TBI patients. ⋯ It is unclear whether these IL-1ra concentrations are sufficient to antagonize the effects of IL-1beta in vivo. This study demonstrates feasibility of our microdialysis methodology in recovering IL-1 family cytokines for assessing their inter-relationships in the injured human brain, and suggests a neuroprotective role for IL-1ra. It remains to be seen whether exogenous IL-1ra or other agents can be used to manipulate cytokine levels in the brain, for potential therapeutic effect.
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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