Journal of neurotrauma
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Journal of neurotrauma · May 2023
Meta AnalysisMajor differences in transcriptional alterations in dorsal root ganglia between spinal cord injury and peripheral neuropathic pain models.
Chronic, often intractable, pain is caused by neuropathic conditions such as traumatic peripheral nerve injury (PNI) and spinal cord injury (SCI). These conditions are associated with alterations in gene and protein expression correlated with functional changes in somatosensory neurons having cell bodies in dorsal root ganglia (DRGs). Most studies of DRG transcriptional alterations have utilized PNI models where axotomy-induced changes important for neural regeneration may overshadow changes that drive neuropathic pain. ⋯ Another unexpected finding was of few transcriptomic similarities between rat neuropathic pain models and the only reported transcriptional analysis of human DRGs linked to neuropathic pain. These findings show that DRGs exhibit complex transcriptional responses to central and peripheral neural injury and associated tissue damage. Although only a few genes in DRG cells exhibited similar changes in expression across all the painful conditions examined here, these genes may represent a core set whose transcription in various DRG cell types is sensitive to significant bodily injury, and which may play a fundamental role in promoting neuropathic pain.
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Journal of neurotrauma · May 2023
ReviewThe spinal cord-gut-immune axis and its implications on therapeutic development for spinal cord injury.
Spinal cord injury (SCI) affects ∼1,300,000 people living in the United States. Most research efforts have been focused on reversing paralysis, as this is arguably the most defining feature of SCI. The damage caused by SCI, however, extends past paralysis and includes other debilitating outcomes including immune dysfunction and gut dysbiosis. ⋯ One exciting avenue is the spinal cord-gut-immune axis, which proposes that gut dysbiosis amplifies lesion inflammation and impairs SCI recovery. This review will highlight the most recent findings regarding gut and immune dysfunction following SCI, and discuss how the central nervous system (CNS), gut, and immune system all coalesce to form a bidirectional axis that can impact SCI recovery. Finally, important considerations regarding how the spinal cord-gut-immune axis fits within the larger framework of therapeutic development (i.e., probiotics, fecal transplants, dietary modifications) will be discussed, emphasizing the lack of interdepartmental investigation and the missed opportunity to maximize therapeutic benefit in SCI.
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Journal of neurotrauma · May 2023
Observational StudyDoes Older Age Affect the Likelihood to Achieve Normal Quality of Life Following Traumatic Spinal Cord Injury? A Prospective Observational Cohort Study.
Previous studies suggest that health-related quality of life (HRQoL) is impaired after a traumatic spinal cord injury (TSCI) and may be worse with older age. This study determines whether the expectations to achieve normal HRQoL in Canadians after a TSCI is indeed influenced by older age. A prospective observational study was conducted on adult patients admitted acutely at a single level-1 trauma center after a TSCI. ⋯ We observed no association between age and achieving normal MCS. A significant proportion of individuals can achieve a normal HRQoL similar to their healthy peers following a TSCI, particularly for the mental component. When compared to younger individuals, older individuals are more likely to achieve normal PCS and present a similar likelihood for achieving normal MCS.
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Journal of neurotrauma · May 2023
A survival model of thoracic contusion spinal cord injury in the domestic pig.
Spinal cord injury (SCI) frequently results in motor, sensory, and autonomic dysfunction for which there is currently no cure. Recent pre-clinical and clinical research has led to promising advances in treatment; however, therapeutics indicating promise in rodents have not translated successfully in human trials, likely due, in part, to gross anatomical and physiological differences between the species. Therefore, large animal models of SCI may facilitate the study of secondary injury processes that are influenced by scale, and may assist the translation of potential therapeutic interventions. ⋯ Regional differences in axonal injury were observed between groups, with amyloid precursor protein immunoreactivity greatest in the 20-cm group in spinal cord sections adjacent to the injury epicenter. This study demonstrated graded injuries in a domestic pig strain, with outcome measures comparable to miniature pig models of contusion SCI. The model provides a vehicle for the study of SCI and potential treatments, particularly where miniature pig strains are not available and/or where small animal models are not appropriate for the research question.
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Journal of neurotrauma · May 2023
Fesoterodine ameliorates autonomic dysreflexia while improving lower urinary tract function and urinary incontinence-related quality of life in individuals with spinal cord injury: A prospective phase IIa study.
The aim of this prospective phase IIa, open-label exploratory, pre-post study was to determine the efficacy of fesoterodine (i.e., 12-week treatment period) to ameliorate autonomic dysreflexia (AD) in individuals with chronic SCI (> 1-year post-injury) at or above the sixth thoracic spinal segment, with confirmed history of AD and neurogenic detrusor overactivity (NDO). Twelve participants (four females, eight males; median age 42 years) completed this study and underwent urodynamics, 24-h ambulatory blood pressure monitoring (ABPM), and urinary incontinence-related quality of life (QoL) measures at baseline and on-treatment. The Montreal Cognitive Assessment (MoCA) and Neurogenic Bowel Dysfunction (NBD) score were used to monitor cognitive and bowel function, respectively. ⋯ AD Frequency (14 vs. 3, p = 0.004) during 24-h ABPM was significantly reduced. Urinary incontinence-related QoL improved (68 vs. 82, p = 0.02), however, cognitive (p = 0.2) and bowel function (p = 0.4) did not change significantly. In conclusion, fesoterodine reduces the magnitude and frequency of AD, while improving LUT function and urinary incontinence-related QoL in individuals with chronic SCI without negatively affecting cognitive or bowel function.