Journal of neurotrauma
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Journal of neurotrauma · Sep 2012
A CD11d monoclonal antibody treatment reduces tissue injury and improves neurological outcome after fluid percussion brain injury in rats.
Traumatic brain injury (TBI) is an international health concern often resulting in chronic neurological abnormalities, including cognitive deficits, emotional disturbances, and motor impairments. An anti-CD11d monoclonal antibody that blocks the CD11d/CD18 integrin and vascular cell adhesion molecule (VCAM)-1 interaction following experimental spinal cord injury improves functional recovery, while reducing the intraspinal number of neutrophils and macrophages, oxidative activity, and tissue damage. Since the mechanisms of secondary injury in the brain and spinal cord are similar, we designed a study to evaluate fully the effects of anti-CD11d treatment after a moderate lateral fluid percussion TBI in the rat. ⋯ At 24 h, the anti-CD11d group performed significantly better than the 1B7 controls on several water maze measures of spatial cognition. At 4 weeks post-injury the anti-CD11d-treated rats had better sensorimotor function as assessed by the beam task, and reduced anxiety-like behaviors, as evidenced by elevated-plus maze testing, compared to 1B7 controls. These findings suggest that neuroinflammation is associated with behavioral deficits after TBI, and that anti-CD11d antibody treatment is a viable strategy to improve neurological outcomes after TBI.
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Journal of neurotrauma · Sep 2012
Multicenter StudyA clinical prediction model for long-term functional outcome after traumatic spinal cord injury based on acute clinical and imaging factors.
To improve clinicians' ability to predict outcome after spinal cord injury (SCI) and to help classify patients within clinical trials, we have created a novel prediction model relating acute clinical and imaging information to functional outcome at 1 year. Data were obtained from two large prospective SCI datasets. Functional independence measure (FIM) motor score at 1 year follow-up was the primary outcome, and functional independence (score ≥ 6 for each FIM motor item) was the secondary outcome. ⋯ Functional independence was achieved by 148 patients (39.4%). For the logistic model, the area under the curve was 0.93 in the original dataset, and 0.92 (95% CI 0.92,0.93) across the bootstraps, indicating excellent predictive discrimination. These models will have important clinical impact to guide decision making and to counsel patients and families.
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Spinal cord injury is a major medical problem worldwide. Unfortunately, we still do not have suitable therapeutic agents for the treatment of spinal cord injury and prevention of its devastating consequences. Scientists and physicians are baffled by the challenges of controlling progressive neurodegeneration in spinal cord injury, which has not been healed with any currently-available treatments. ⋯ Several investigators reported the crucial role played by various proteases after spinal cord injury. Understanding the beneficial and harmful roles these proteases play after spinal cord injury will allow scientists to plan and design appropriate treatment strategies to improve functional recovery after spinal cord injury. This review will focus on various proteases such as matrix metalloproteinases, cysteine proteases, and serine proteases and their inhibitors in the context of spinal cord injury.
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Journal of neurotrauma · Sep 2012
Comparative StudyThe effect of injury severity on behavior: a phenotypic study of cognitive and emotional deficits after mild, moderate, and severe controlled cortical impact injury in mice.
Traumatic brain injury (TBI) can cause a broad array of behavioral problems including cognitive and emotional deficits. Human studies comparing neurobehavioral outcomes after TBI suggest that cognitive impairments increase with injury severity, but emotional problems such as anxiety and depression do not. To determine whether cognitive and emotional impairments increase as a function of injury severity we exposed mice to sham, mild, moderate, or severe controlled cortical impact (CCI) and evaluated performance on a variety of neurobehavioral tests in the same animals before assessing lesion volume as a histological measure of injury severity. ⋯ Stepwise regression analyses revealed that Morris water maze performance and torso flexion predicted the majority of the variability in lesion volume. In summary, we find that cognitive deficits increase in relation to injury severity, but emotional deficits do not. Our data suggest that the threshold for emotional changes after experimental TBI is low, with no variation in behavioral deficits seen between mild and severe brain injury.