Journal of neurotrauma
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Journal of neurotrauma · May 2015
Endothelial nitric oxide synthase mediates arteriolar vasodilatation after traumatic brain injury in mice.
Brain edema and increased cerebral blood volume (CBV) contribute to intracranial hypertension and hence to unfavorable outcome after traumatic brain injury (TBI). The increased post-traumatic CBV may be caused in part by arterial vasodilatation. The aim of the current study was to uncover the largely unknown mechanisms of post-traumatic arteriolar vasodilatation. ⋯ The diameter of pial veins was not affected. Our results suggest that arteriolar vasodilatation after TBI is largely mediated by excess production of endothelial nitric oxide. Accordingly, our data may explain the beneficial effects of the NOS inhibitor VAS203 in the early phase after TBI and suggest that inhibition of excess endothelial nitric oxide production may represent a novel therapeutic strategy following TBI.
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Journal of neurotrauma · May 2015
Fluoxetine prevents oligodendrocyte cell death by inhibiting microglia activation after spinal cord injury.
Oligodendrocyte cell death and axon demyelination after spinal cord injury (SCI) are known to be important secondary injuries contributing to permanent neurological disability. Thus, blocking oligodendrocyte cell death should be considered for therapeutic intervention after SCI. Here, we demonstrated that fluoxetine, an antidepressant drug, alleviates oligodendrocyte cell death by inhibiting microglia activation after SCI. ⋯ In addition, fluoxetine attenuated activation of Ras homolog gene family member A and decreased the level of phosphorylated c-Jun and, ultimately, alleviated caspase-3 activation and significantly reduced cell death of oligodendrocytes at 5 days after SCI. Further, the decrease of myelin basic protein, myelin loss, and axon loss in white matter was also significantly blocked by fluoxetine, as compared to vehicle control. These results suggest that fluoxetine inhibits oligodendrocyte cell death by inhibiting microglia activation and p38-MAPK activation, followed by pro-NGF production after SCI, and provide a potential usage of fluoxetine for a therapeutic agent after acute SCI in humans.
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Journal of neurotrauma · May 2015
An Intensive Locomotor Training Paradigm Improves Neuropathic Pain following Spinal Cord Compression Injury in Rats.
Spinal cord injury (SCI) is often associated with both locomotor deficits and sensory dysfunction, including debilitating neuropathic pain. Unfortunately, current conventional pharmacological, physiological, or psychological treatments provide only marginal relief for more than two-thirds of patients, highlighting the need for improved treatment options. Locomotor training is often prescribed as an adjunct therapy for peripheral neuropathic pain but is rarely used to treat central neuropathic pain. ⋯ ILT prevented and reversed the development of heat hyperalgesia and cold allodynia, as well as reversed developed tactile allodynia, suggesting analgesic benefits not seen with moderate levels of locomotor training. Further, the analgesic benefits of ILT persisted for several weeks once training had been stopped. The unique ability of an ILT protocol to produce robust and sustained anti-nociceptive effects, as assessed by three distinct outcome measures for below-level SCI neuropathic pain, suggests that this adjunct therapeutic approach has great promise in a comprehensive treatment strategy for SCI pain.
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Journal of neurotrauma · May 2015
Multicenter Study Comparative Study Observational StudyThe influence of time from injury to surgery on motor recovery and length of hospital stay in acute traumatic spinal cord injury: an observational Canadian cohort study.
To determine the influence of time from injury to surgery on neurological recovery and length of stay (LOS) in an observational cohort of individuals with traumatic spinal cord injury (tSCI), we analyzed the baseline and follow-up motor scores of participants in the Rick Hansen Spinal Cord Injury Registry to specifically assess the effect of an early (less than 24 h from injury) surgical procedure on motor recovery and on LOS. One thousand four hundred and ten patients who sustained acute tSCIs with baseline American Spinal Injury Association Impairment Scale (AIS) grades A, B, C, or D and were treated surgically were analyzed to determine the effect of the timing of surgery (24, 48, or 72 h from injury) on motor recovery and LOS. Depending on the distribution of data, we used different types of generalized linear models, including multiple linear regression, gamma regression, and negative binomial regression. ⋯ AIS A and B patients who received early surgery experienced shorter hospital LOS. While the issues of when to perform surgery and what specific operation to perform remain controversial, this work provides evidence that for an incomplete acute tSCI in the cervical, thoracic, or thoracolumbar spine, surgery performed within 24 h from injury improves motor neurological recovery. Early surgery also reduces LOS.
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Journal of neurotrauma · May 2015
ReviewNeuroprotection, plasticity manipulation, and regenerative strategies to improve cardiovascular function following spinal cord injury.
Damage to the central nervous system, as in the case of spinal cord injury (SCI), results in disrupted supraspinal sympathetic influence and subsequent cardiovascular control impairments. Consequently, people with SCI suffer from disordered basal hemodynamics and devastating fluctuations in blood pressure, as in the case of autonomic dysreflexia (AD), which likely contribute to this population's leading cause of mortality: cardiovascular disease. The development of AD is related, at least in part, to neuroanatomical changes that include disrupted descending supraspinal sympathetic control, changes in propriospinal circuitry, and inappropriate afferent sprouting in the dorsal horn. ⋯ Here, we discuss the relationship between abnormal cardiovascular control and its underlying neuroanatomy. We then review current studies investigating biochemical strategies to reduce the severity of AD through: 1) reducing aberrant calcitonin gene-related peptide immunoreactive afferent sprouting; 2) inhibiting inflammatory processes; and 3) re-establishing descending supraspinal sympathetic control. Finally, we discuss why additional biochemical agents and combinational approaches may be needed to completely ameliorate this condition.