Journal of neurotrauma
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Journal of neurotrauma · Apr 2010
Clinical TrialCerebrospinal fluid inflammatory cytokines and biomarkers of injury severity in acute human spinal cord injury.
There is an urgent need for both the scientific development and clinical validation of novel therapies for acute spinal cord injury (SCI). The scientific development of novel therapies would be facilitated by a better understanding of the acute pathophysiology of human SCI. Clinical validation of such therapies would be facilitated by the availability of biomarkers with which to stratify injury severity and predict neurological recovery. ⋯ Furthermore, segmental motor recovery at 6 months post injury was better predicted by these CSF proteins than with the patients' baseline ASIA grade. The pattern of expression over the first 3 to 4 days post injury of a number of inflammatory cytokines such as IL-6, IL-8, and MCP-1 provides invaluable information about the pathophysiology of human SCI. A prediction model that could use such biological data to stratify injury severity and predict neurological outcome may be extremely useful for facilitating the clinical validation of novel treatments in acute human SCI.
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Journal of neurotrauma · Apr 2010
Hyperoxic reperfusion after global cerebral ischemia promotes inflammation and long-term hippocampal neuronal death.
In this study we tested the hypothesis that long-term neuropathological outcome is worsened by hyperoxic compared to normoxic reperfusion in a rat global cerebral ischemia model. Adult male rats were anesthetized and subjected to bilateral carotid arterial occlusion plus bleeding hypotension for 10 min. The rats were randomized to one of four protocols: ischemia/normoxia (21% oxygen for 1 h), ischemia/hyperoxia (100% oxygen for 1 h), sham/normoxia, and sham/hyperoxia. ⋯ Behavioral deficits were also observed following hyperoxic, but not normoxic, reperfusion. We conclude that early post-ischemic hyperoxic reperfusion is followed by greater hippocampal neuronal death and cellular inflammatory reactions compared to normoxic reperfusion. The results of these long-term outcome studies, taken together with previously published results from short-term experiments performed with large animals, support the hypothesis that neurological outcome can be improved by avoiding hyperoxic resuscitation after global cerebral ischemia such as that which accompanies cardiac arrest.
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Journal of neurotrauma · Apr 2010
The whisker nuisance task identifies a late-onset, persistent sensory sensitivity in diffuse brain-injured rats.
Post-traumatic morbidity reduces the quality of life for traumatic brain injury (TBI) survivors by altering neuropsychological function. After midline fluid percussion injury (FPI), diffuse pathology in the ventral posterior thalamus suggests that somatosensory whisker function may be impaired post-injury. The goals of the present study were to design and validate a task to detect injury-induced somatosensory morbidity (Experiment 1), and to evaluate preliminary applications of the task (Experiment 2). ⋯ In Experiment 2, to evaluate applications of the whisker nuisance task, four additional uninjured and brain-injured groups were subjected to mild brain injury only, shaved whiskers after moderate brain injury, repeated whisker nuisance task stimulation after moderate brain injury, or regular opportunities for tactile exploration of an enriched environment after moderate brain injury over 4 weeks post-injury. The whisker nuisance task has the sensitivity to detect mild brain injury (7.7 +/- 1.0), but morbidity was not mitigated by any of the neurorehabilitative interventions. Following diffuse brain injury, the whisker nuisance task is a promising tool to detect post-traumatic morbidity and the efficacy of therapeutic interventions that may restore discrete circuit function in brain-injured patients.
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Journal of neurotrauma · Apr 2010
Loss of GABAergic interneurons in laminae I-III of the spinal cord dorsal horn contributes to reduced GABAergic tone and neuropathic pain after spinal cord injury.
Abstract In this study we explore if loss of GABAergic inhibitory interneurons in the superficial dorsal horn of the spinal cord contributes to reduced GABAergic tone and neuropathic pain following spinal cord injury (SCI). A moderate contusion injury to T11 resulted in the development of mechanical hyperalgesia and thermal hyperalgesia below the level of the lesion in gad1:GFP mice that were alleviated by IP administration of the GABA transporter antagonist tiagabine. Six weeks following SCI a decreased number of GFP(+) neurons were observed in the dorsal horn of SCI animals relative to sham mice. ⋯ Reversal of post-SCI neuropathic pain by tiagabine suggests that reduced GABAergic tone may contribute to hyperalgesia symptoms. This is supported by the subsequent observation that SCI reduced the number of GFP(+) inhibitory neurons, and the finding that some GABAergic GFP(+) neurons undergo cell death at a time point consistent with the development of neuropathic pain following SCI. Concordantly, reductions in both GAD65 and GAD67 and GAT1 immunoreactivity also support the observation of a loss of GABAergic inhibition and the associated spinal interneurons.