Journal of neurotrauma
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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.
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Journal of neurotrauma · May 2023
Differential Trajectory of Diffusion and Perfusion MRI of Rat Spinal Cord Injury.
Traumatic spinal cord injury causes rapid neuronal and vascular injury, and predictive biomarkers are needed to facilitate acute patient management. This study examined the progression of magnetic resonance imaging (MRI) biomarkers after spinal cord injury and their ability to predict long-term neurological outcomes in a rodent model, with an emphasis on diffusion-weighted imaging (DWI) markers of axonal injury and perfusion-weighted imaging of spinal cord blood flow (SCBF). Adult Sprague-Dawley rats received a cervical contusion injury of varying severity (injured = 30, sham = 9). ⋯ At 48 h, SCBF (R2 = 0.41, padj < 0.01) became less associated with outcome, and DWI (R2 = 0.38, padj < 0.01) lesion volume became more closely related to outcome. Spinal cord perfusion has unique spatiotemporal dynamics compared with diffusion measures of axonal damage and highlights the importance of acute perfusion abnormalities. Perfusion and diffusion offer complementary and clinically relevant insight into physiological and structural abnormalities following spinal cord injury beyond those afforded by T1 or T2 contrasts.
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Journal of neurotrauma · May 2023
Acute pharmacological inhibition of PERK signaling after spinal cord injury spares oligodendrocytes and improves locomotor recovery.
Protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) is a major signal transducer of the endoplasmic reticulum stress response (ERSR) pathway. Outcomes of PERK activation range from abrogating ER stress to induction of cell death, dependent on its level, duration, and cellular context. Current data demonstrate that after mouse spinal cord injury (SCI), acute inhibition of PERK (0-72 h) with the small molecule inhibitor GSK2656157 reduced ERSR while improving white matter sparing and hindlimb locomotion recovery. ⋯ Moreover, GSK2656157 protected cultured primary mouse oligodendrocyte precursor cells from ER stress-induced cytotoxicity. These findings suggest that in the context of SCI, excessive acute activation of PERK contributes to functionally relevant white matter damage. Pharmacological inhibition of PERK is a potential strategy to protect central nervous system (CNS) white matter following acute injuries, including SCI.
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Journal of neurotrauma · May 2023
Corticospinal control of a challenging ankle task in incomplete spinal cord injury.
After incomplete spinal cord injury (iSCI), the control of lower extremity movements may be affected by impairments in descending corticospinal tract function. Previous iSCI studies demonstrated relatively well-preserved movement control during simple alternating dorsiflections and plantar flexions albeit with severely reduced motor strength and range of motion. This task, however, required comparably limited fine motor control, impeding the sensitivity to assess the modulatory capacity of corticospinal control. ⋯ These results, along with the walking performance, correlated well with the delta frequency shift between the regular and irregular movement task in the 38 Hz band (corticospinal drive frequency) in the iSCI group, suggesting that task performance is related to the capacity to modulate corticospinal control. The irregular movement task holds promise as a tool for revealing further insights into corticospinal control of single-joint movements. It may serve as a surrogate marker for the assessment of modulatory capacity and the integrity of corticospinal control in individuals with iSCI early after injury and throughout rehabilitation.
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Spinal cord injury (SCI) results in significant loss of sublesional bone, adding to the comorbidity of SCI with an increased risk of fracture and post-fracture complications. Unfortunately, the effect of SCI on skeletal health is also likely to rise, as the average age of SCI has increased and there are well-known negative effects of age on bone. To date, however, the impact of age and age-associated inflammation (inflammaging) on skeletal health after SCI remains largely unknown. ⋯ In fact, SCI had more dramatic and persistent effects on bone in male rats, whereas aging and SCI elevated serum cytokines only in female rats. Overall, this study demonstrates SCI-induced loss of bone and altered bone turnover in male and female rats that persists into the chronic phase post-injury. The sex- and age-dependent variations in bone turnover and serum cytokines, however, underscore the need to further explore both mechanisms and potential therapeutics in multiple demographics.