Journal of neurotrauma
-
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.
-
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.
-
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.
-
Journal of neurotrauma · May 2015
Spinal cord injury is related to an increased risk of multiple sclerosis: a population-based, propensity score-matched, longitudinal follow-up study.
Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system (CNS). Trauma to the CNS has been postulated to play a role in triggering CNS autoimmune disease. Although the association between traumatic brain injury and MS has been suggested in previous studies, epidemiological data on the association between spinal cord injury (SCI) and MS is still lacking. ⋯ The incidence rates of MS were 17.60 (95% confidence interval [CI], 5.71-41.0) per 100,000 person-years in the SCI group and 2.82 (95% CI, 0.77-7.22) per 100,000 person-years in the non-SCI group. Compared with the non-SCI group, the hazard ratio of MS for the SCI group was 8.33 (95% CI, 1.99-34.87, p=0.0037). Our study therefore shows that patients with SCI have an increased risk of developing MS.