Journal of neurotrauma
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Journal of neurotrauma · Mar 2008
Evolution of post-traumatic neurodegeneration after controlled cortical impact traumatic brain injury in mice and rats as assessed by the de Olmos silver and fluorojade staining methods.
This report documents an analysis of post-traumatic neurodegeneration during the first 7 days after controlled cortical impact (CCI) traumatic brain injury (TBI) in mice and rats using the de Olmos aminocupric silver staining method, which selectively stains degenerating axons and nerve terminals, compared to the fluorojade method, which stains degenerating neuronal cell bodies. A progressive increase in cortical, hippocampal, and thalamic degeneration was observed over the first 48 h after injury in both species. Approximately 50% of the ipsilateral cortical volume was stained at 48 h. ⋯ These results show that previous CCI studies which have relied on conventional histological methods that show cell body staining alone have underestimated the degree of axonal damage associated with the CCI-TBI model. In order to capture the full extent of the injury to both axons and cell bodies, the combination of silver staining and fluorojade staining is needed, respectively. Future studies of potential neuroprotective agents should probably not rely on the measure of cortical lesion volume or volume of spared cortical tissue using conventional histological stains alone, since these fail to identify the complete extent of the posttraumatic neuropathology that some agents which reduce cortical lesion volume may not be able to effect.
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Journal of neurotrauma · Mar 2008
Post-injury atomoxetine treatment improves cognition following experimental traumatic brain injury.
Catecholaminergic neurotransmission is regionally altered following injury, and drugs aimed at these systems offer promising avenues for post-traumatic brain injury (TBI) pharmacotherapies. Atomoxetine is a selective norepinephrine transporter (NET) inhibitor currently indicated for treatment of attention-deficit hyperactivity disorder (ADHD). The current study was designed to test the efficacy of atomoxetine in treating cognitive deficits following experimental TBI in animals and to determine an optimal dose and therapeutic window for drug treatment. ⋯ Rats were administered atomoxetine daily for 15 days, and cognitive assessment was performed on PID 25-29. In this study, treatment with atomoxetine (1 mg/kg) did not result in improved cognitive performance. In conclusion, this is the first study to show low-dose atomoxetine initiated early after experimental TBI results in improved cognition.
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Journal of neurotrauma · Mar 2008
Interleukin-6 and nerve growth factor upregulation correlates with improved outcome in children with severe traumatic brain injury.
Secondary brain damage after traumatic brain injury (TBI) involves neuro-inflammatory mechanisms that are mainly dependent on the intracerebral production of cytokines. Interleukin-6 (IL-6) may have a role both in the pathogenesis of neuronal damage and in the recovery mechanisms of injured neurons through the modulation of nerve growth factor (NGF) biosynthesis. However, the relationship between IL-6 and NGF expression and the severity and outcome of TBI remains controversial. ⋯ Furthermore, IL-6 and NGF upregulation after injury was associated with better neurologic outcomes. Based on these findings, we posit that NGF expression is a useful marker of brain damage following severe TBI. Moreover, the early upregulation of both IL-6 and NGF, which correlates with a favorable neurologic outcome, may reflect an endogenous attempt at neuroprotection in response to the damaging biochemical and molecular cascades triggered by traumatic insult.
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Journal of neurotrauma · Mar 2008
Laminectomy and fusion after spinal cord injury: national inpatient complications and outcomes.
There is little information about national in-hospital complication rates, adverse outcomes, and mortality after spinal fusion for spinal cord injury (SCI). The National Inpatient Sample (NIS) was utilized to identify 31,381 admissions of acute spinal cord injured patients who underwent spinal decompression with laminectomy and/or fusion (lam/fusion) in the United States from 1993 to 2002. Multivariate analysis was performed to analyze the effects of patient and hospital characteristics on outcomes such as mortality, complications, and discharge disposition, which were then stratified by age, level, and type of injury. ⋯ Patients with >3 comorbidities also had an increased risk of mortality (odds ratio [OR] = 1.8). Alcohol abuse was the most common medical comorbidity (present in 12% of patients treated). This study represents the first major national estimate of in-hospital mortality and complication rates after nonoperative and operative treatment for SCI.
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Journal of neurotrauma · Mar 2008
Erythropoietin potentiates EDHF-mediated dilations in rat middle cerebral arteries.
The neuroprotective effects of exogenous erythropoietin (EPO) in animals and humans after brain injury may be afforded, in part, by the influence of EPO on cerebral arteries. We tested (1) if EPO itself is vasoactive and (2) if EPO enhances endothelium-mediated dilations, specifically those mediated by endothelium-derived hyperpolarizing factor (EDHF). Immunoblotting and reverse transcriptase-polymerase chain reaction (RT-PCR) were used to detect EPO receptor. ⋯ This study demonstrates that EPO can directly dilate rat MCAs via the endothelium, though not all vessels are responsive. Additionally, pre-treatment with EPO for 24 h in vivo potentiates endothelium-mediated dilations, specifically those mediated by EDHF. Thus, enhanced endothelium-mediated dilations may partially underlie the neuroprotective effects of EPO after brain injury.