Muscle-restricted knockout of connexin 43 and connexin 45 accelerates and improves locomotor recovery after contusion spinal cord injury.

Traumatic spinal cord injury (SCI) results in the disruption of physiological systems below the level of the spinal lesion. Connexin hemichannels (CxHCs) are membrane-bound, non-selective pore proteins that are lost in mature myofibers but reappear on the sarcolemma after peripheral denervation, chronic SCI, diabetes, and severe systemic stress such as sepsis. Cx43 and Cx45 have been implicated as the major CxHCs present in diseased muscle, and muscle-restricted knockout of these genes reduces muscle atrophy after denervation, likely by reducing excess calcium influx with resultant inflammasome activation.

Administration of low intensity vibration and a RANKL inhibitor, alone or in combination, reduces bone loss after spinal cord injury-induced immobilization in rats.

We previously reported an ability of low-intensity vibration (LIV) to improve selected biomarkers of bone turnover and gene expression and reduce osteoclastogenesis but lacking of evident bone accrual. In this study, we demonstrate that a prolonged course of LIV that initiated at 2 weeks post-injury and continued for 8 weeks can protect against bone loss after SCI in rats. LIV stimulates bone formation and improves osteoblast differentiation potential of bone marrow stromal stem cells while inhibiting osteoclast differentiation potential of marrow hematopoietic progenitors to reduce bone resorption.

Exoskeletal-assisted walking combined with transcutaneous spinal cord stimulation to improve bone health in persons with spinal cord injury: study protocol for a prospective randomised controlled trial.

Introduction: Persons with non-ambulatory spinal cord injury (SCI) undergo immediate unloading of the skeleton and, as a result, have marked loss of bone mineral density below the level of lesion that is directly associated with increased risk of long-bone fractures. There is a paucity of research that has successfully implemented rehabilitation and/or exercise training interventions to mitigate bone loss after acute SCI or reverse bone loss that has already occurred in chronic SCI. This paper describes a research protocol to compare the effect of exoskeletal-assisted walking (EAW) alone versus EAW plus transcutaneous spinal cord stimulation (EAW+tSCS) on bone density, geometry and strength in a cohort of chronic SCI participants.

Targeted-delivery of nanomedicine-enabled methylprednisolone to injured spinal cord promotes neuroprotection and functional recovery after acute spinal cord injury in rats.

To date, no therapy has been proven to be efficacious in fully restoring neurological functions after spinal cord injury (SCI). Systemic high-dose methylprednisolone (MP) improves neurological recovery after acute SCI in both animal and human. MP therapy remains controversial due to its modest effect on functional recovery and significant adverse effects.

Anti-Siglec-15 Antibody Prevents Marked Bone Loss after Acute Spinal Cord Injury-Induced Immobilization in Rats.

Rapid and extensive sublesional bone loss after spinal cord injury (SCI) is a difficult medical problem that has been refractory to available interventions except the antiresorptive agent denosumab (DMAB). While DMAB has shown some efficacy in inhibiting bone loss, its concurrent inhibition of bone formation limits its use. Sialic acid-binding immunoglobulin-like lectin (Siglec)-15 is expressed on the cell surface of mature osteoclasts.

Lack of improvement in anorectal manometry parameters after implementation of a pelvic floor/anal sphincter biofeedback in persons with motor-incomplete spinal cord injury.

Background: Effect of biofeedback on improving anorectal manometric parameters in incomplete spinal cord injury is unknown. A short-term biofeedback program investigated any effect on anorectal manometric parameters without correlation to bowel symptoms.

Methods: This prospective uncontrolled interventional study comprised three study subject groups, Group 1: sensory/motor-complete American Spinal Injury Association Impairment Scale (AIS) A SCI (n = 13); Group 2 (biofeedback group): sensory incomplete AIS B SCI (n = 17) (n = 3), and motor-incomplete AIS C SCI (n = 8), and AIS D SCI (n = 6); and Group 3: able-bodied (AB) controls (n = 12).

Cardiometabolic risk factor clustering in persons with spinal cord injury: A principal component analysis approach.

Context/objective: To identify cardiometabolic (CM) measurements that cluster to confer increased cardiovascular disease (CVD) risk using principal component analysis (PCA) in a cohort of chronic spinal cord injury (SCI) and healthy non-SCI individuals.

Approach: A cross-sectional study was performed in ninety-eight non-ambulatory men with chronic SCI and fifty-one healthy non-SCI individuals (ambulatory comparison group). Fasting blood samples were obtained for the following CM biomarkers: lipid, lipoprotein particle, fasting glucose and insulin concentrations, leptin, adiponectin, and markers of inflammation.

Abaloparatide prevents immobilization-induced cortical but not trabecular bone loss after spinal cord injury.

Spinal cord injury (SCI) causes severe and resistant sublesional disuse bone loss. Abaloparatide, a modified parathyroid hormone related peptide, is an FDA approved drug for treatment of severe osteoporosis with potent anabolic activity. The effects of abaloparatide on SCI-induced bone loss remain undefined.

Preliminary observations on the administration of a glucagon-like peptide-1 receptor agonist on body weight and select carbohydrate endpoints in persons with spinal cord injury: A controlled case series.

Context/objective: To describe the effect of semaglutide, a glucagon-like peptide-1 (GLP-1) agonist, to reduce body weight and improve glycemic control in overweight or obese individuals with spinal cord injury (SCI).

Design: Open-label, randomized drug intervention case series.

Setting: This study was performed at James J.

Self-reported effects of warm seasonal temperatures in persons with spinal cord injury.

Objective: Spinal cord injury (SCI) interrupts motor, sensory, and autonomic pathways, impairing mobility and increasing heat storage during warm seasonal temperatures due to compromised autonomic control of vasodilation and sweating and recognition of body temperature. Thus, persons with SCI are more vulnerable to hyperthermia and its adverse effects. However, information regarding how persons with SCI perceive warmer seasons and whether thermal discomfort during warmer seasons restricts routine activities remains anecdotal.

Clinical trial of home blood pressure monitoring following midodrine administration in hypotensive individuals with spinal cord injury.

Background: Individuals with spinal cord injury (SCI) above thoracic level-6 (T6) experience impaired descending cortical control of the autonomic nervous system which predisposes them to blood pressure (BP) instability, including includes hypotension, orthostatic hypotension (OH), and autonomic dysreflexia (AD). However, many individuals do not report symptoms of these BP disorders, and because there are few treatment options that have been proven safe and effective for use in the SCI population, most individuals remain untreated.

Objective: The primary aim of this investigation was to determine the effects of midodrine (10 mg) prescribed TID or BID in the home environment, compared to placebo, on 30-day BP, study withdrawals, and symptom reporting associated with OH and AD in hypotensive individuals with SCI.

Denervation Atrophy of Skeletal Muscle is Not Influenced by Numb Levels in Mice.

Skeletal muscle undergoes rapid and extensive atrophy following nerve transection though the underlying mechanisms remain incompletely understood. We previously showed transiently elevated Notch 1 signaling in denervated skeletal muscle that was abrogated by administration of nandrolone (an anabolic steroid) combined with replacement doses of testosterone. Numb is an adaptor molecule present in myogenic precursors and skeletal muscle fibers that is vital for normal tissue repair after muscle injury and for skeletal muscle contractile function.

Comparison of the dynamics of exoskeletal-assisted and unassisted locomotion in an FDA-approved lower extremity device: Controlled experiments and development of a subject-specific virtual simulator.

Robotic exoskeletons have considerable, but largely untapped, potential to restore mobility in individuals with neurological disorders, and other conditions that result in partial or complete immobilization. The growing demand for these devices necessitates the development of technology to characterize the human-robot system during exoskeletal-assisted locomotion (EAL) and accelerate robot design refinements. The goal of this study was to combine controlled experiments with computational modeling to build a virtual simulator of EAL.

Loss of lower extremity bone mineral density 1 year after denosumab is discontinued in persons with subacute spinal cord injury.

Unlabelled: Twelve months following discontinuation of denosumab, the percent decrease in mean bone mineral density (BMD) values at the hip and knee regions were similar between both the denosumab and placebo groups. These findings emphasize the need for additional trials to understand the effect of continued administration of denosumab after subacute spinal cord injury (SCI) to avoid this demineralization.

Objective: To determine changes in BMD 1 year after denosumab was discontinued in participants with subacute SCI who had drug treatment initiated within 90 days post SCI and continued for 1 year.

Myostatin inhibits insulin-like growth factor 1-dependent citrate secretion and osteogenesis via nicotinamide adenine dinucleotide phosphate oxidase-4 in a mouse mesenchymal stem cell line.

Citrate is an indispensable component of bone. Reduced levels of citrate in bone and serum are reported in the elderly and in osteoporosis patients. Myostatin (Mstn) is implicated in skeletal homeostasis, but its effects on osteogenesis remain incompletely understood.

Generation of a Reference Dataset to Permit the Calculation of T-scores at the Distal Femur and Proximal Tibia in Persons with Spinal Cord Injury.

Persons with traumatic spinal cord injury (SCI) have severe bone loss below the level of lesion with the distal femur (DF) and proximal tibia (PT) being the skeletal regions having the highest risk of fracture. While a reference areal bone mineral density (aBMD) database is available at the total hip (TH) using the combined National Health and Nutrition Examination Survey (NHANES) III study and General Electric (GE) combined (GE/NHANES) to calculate T-score (T-score), no such reference database exists for aBMD of the DF, and PT. The primary objectives of this study were (1) to create a reference dataset of young-healthy able-bodied (YHAB) persons to calculate T-score (T-score) values at the DF and PT, (2) to explore the impact of time since injury (TSI) on relative bone loss in the DF and PT regions using the two computation models to determine T-score values, and (3) to determine agreement between T-score values for a cohort of persons with SCI using the (T-score) and (T-score) reference datasets.

Administration of High-Dose Methylprednisolone Worsens Bone Loss after Acute Spinal Cord Injury in Rats.

The administration of high-dose methylprednisolone (MP) for 24-48 h after traumatic spinal cord injury (SCI) has been shown to improve functional recovery. The known adverse effects of MP on skeletal muscle and the immune system, though, have raised clinically relevant safety concerns. However, the effect of MP administration on SCI-induced bone loss has not been evaluated to date.

Numb is required for optimal contraction of skeletal muscle.

Background: The role of Numb, a protein that is important for cell fate and development and that, in human muscle, is expressed at reduced levels with advanced age, was investigated; adult mice skeletal muscle and its localization and function within myofibres were determined.

Methods: Numb expression was evaluated by western blot. Numb localization was determined by confocal microscopy.

Inhibition of TGF-β Signaling Attenuates Disuse-induced Trabecular Bone Loss After Spinal Cord Injury in Male Mice.

Bone loss is one of the most common complications of immobilization after spinal cord injury (SCI). Whether transforming growth factor (TGF)-β signaling plays a role in SCI-induced disuse bone loss has not been determined. Thus, 16-week-old male mice underwent sham or spinal cord contusion injury to cause complete hindlimb paralysis.

Pharmacological approaches for bone health in persons with spinal cord injury.

Spinal cord injury (SCI) results in rapid, marked skeletal deterioration below the level of neurological lesion. Ideally, the most effective therapeutic approach would prevent loss of bone mass and architecture shortly after paralysis. Bisphosphonates preserve bone mineral density at the hip but not at the knee, which is the anatomical site most prone to fracture in the SCI population.

Effects of a High-Fat Diet on Tissue Mass, Bone, and Glucose Tolerance after Chronic Complete Spinal Cord Transection in Male Mice.

Spinal cord injury (SCI) is associated with obesity and is a risk factor for type 2 diabetes mellitus (T2DM). Immobilization, muscle atrophy, obesity, and loss of sympathetic innervation to the liver are believed to contribute to risks of these abnormalities. Systematic study of the mechanisms underlying SCI-induced metabolic disorders has been limited by a lack of animal models of insulin resistance following SCI.

Predicting Cardiometabolic Risk From Visceral Abdominal Adiposity in Persons With Chronic Spinal Cord Injury.

Persons with spinal cord injury (SCI) have increased adiposity that may predispose to cardiovascular disease compared to those who are able-bodied (AB). The purpose of this study was to determine the relationships between dual energy X-ray absorptiometry (DXA)-derived visceral adipose tissue (VAT) and biomarkers of lipid metabolism and insulin resistance in persons with chronic SCI. A prospective observational study in participants with chronic SCI and age- and gender-matched AB controls.