Early movement restriction impairs the development of sensorimotor integration, motor skills and memory in rats: Towards a preclinical model of developmental coordination disorder?

Children with neurodevelopmental disorders, such as developmental coordination disorder (DCD), exhibit gross to fine sensorimotor impairments, reduced physical activity and interactions with the environment and people. This disorder co-exists with cognitive deficits, executive dysfunctions and learning impairments. Previously, we demonstrated in rats that limited amounts and atypical patterns of movements and somatosensory feedback during early movement restriction manifested in adulthood as degraded postural and locomotor abilities, and musculoskeletal histopathology, including muscle atrophy, hyperexcitability within sensorimotor circuitry and maladaptive cortical plasticity, leading to functional disorganization of the primary somatosensory and motor cortices in the absence of cortical histopathology.

Potentiation of Collagen Deposition by the Combination of Substance P with Transforming Growth Factor Beta in Rat Skin Fibroblasts.

A role for substance P has been proposed in musculoskeletal fibrosis, with effects mediated through transforming growth factor beta (TGFβ). We examined the in vitro effects of substance P on proliferation, collagen secretion, and collagen deposition in rat primary dermal fibroblasts cultured in medium containing 10% fetal bovine serum, with or without TGFβ. In six-day cultures, substance P increased cell proliferation at concentrations from 0.

Poor sleep versus exercise: A duel to decide whether pain resolves or persists after injury.

Poor sleep is thought to enhance pain via increasing peripheral and/or central sensitization. Aerobic exercise, conversely, relives pain via reducing sensitization, among other mechanisms. This raises two clinical questions: (1) does poor sleep contribute to the transition from acute-to-persistent pain, and (2) can exercise protect against this transition? This study tested these questions and explored underlying mechanisms in a controlled injury model.

Extracellular Acetylated Histone 3.3 Induces Inflammation and Lung Tissue Damage.

Extracellular histones, part of the protein group known as damage-associated molecular patterns (DAMPs), are released from damaged or dying cells and can instigate cellular toxicity. Within the context of chronic obstructive pulmonary disease (COPD), there is an observed abundance of extracellular histone H3.3, indicating potential pathogenic implications.

Blocking CCN2 Reduces Established Bone Loss Induced by Prolonged Intense Loading by Increasing Osteoblast Activity in Rats.

We have an operant model of reaching and grasping in which detrimental bone remodeling is observed rather than beneficial adaptation when rats perform a high-repetition, high-force (HRHF) task long term. Here, adult female Sprague-Dawley rats performed an intense HRHF task for 18 weeks, which we have shown induces radial trabecular bone osteopenia. One cohort was euthanized at this point (to assay the bone changes post task; HRHF-Untreated).

Dog and human bladders have different neurogenic and nicotinic responses in inner versus outer detrusor muscle layers.

The aim of this study was to investigate layer and species variations in detrusor muscle strip responses to myogenic, neurogenic, and nicotinic, and muscarinic receptor stimulations. Strips from bladders of 9 dogs and 6 human organ transplant donors were dissected from inner and outer longitudinal muscle layers, at least 1 cm above urethral orifices. Strips were mounted in muscle baths and maximal responses to neurogenic stimulation using electrical field stimulation (EFS) and myogenic stimulation using potassium chloride (KCl, 120 mM) determined.

Manual Therapy Facilitates Homeostatic Adaptation to Bone Microstructural Declines Induced by a Rat Model of Repetitive Forceful Task.

The effectiveness of manual therapy in reducing the catabolic effects of performing repetitive intensive force tasks on bones has not been reported. We examined if manual therapy could reduce radial bone microstructural declines in adult female Sprague-Dawley rats performing a 12-week high-repetition and high-force task, with or without simultaneous manual therapy to forelimbs. Additional rats were provided 6 weeks of rest after task cessation, with or without manual therapy.

Manual Therapy With Rest as a Treatment for Established Inflammation and Fibrosis in a Rat Model of Repetitive Strain Injury.

: Repetitive strain injuries caused by repetitive occupational work are difficult to prevent for multiple reasons. Therefore, we examined the effectiveness of manual therapy (MT) with rest to treat the inflammation and fibrosis that develops through the performance of a repetitive task. We hypothesized that this treatment would reduce task-induced sensorimotor declines and neuromuscular inflammation.

Key indicators of repetitive overuse-induced neuromuscular inflammation and fibrosis are prevented by manual therapy in a rat model.

Background: We examined the effectiveness of a manual therapy consisting of forearm skin rolling, muscle mobilization, and upper extremity traction as a preventive treatment for rats performing an intensive lever-pulling task. We hypothesized that this treatment would reduce task-induced neuromuscular and tendon inflammation, fibrosis, and sensorimotor declines.

Methods: Sprague-Dawley rats performed a reaching and lever pulling task for a food reward, 2 h/day, 3 days/week, for 12 weeks, while simultaneously receiving the manual therapy treatment 3 times per week for 12 weeks to either the task-involved upper extremities (TASK-Tx), or the lower extremities as an active control group (TASK-Ac).

Nerve transfer for restoration of lower motor neuron-lesioned bladder function. Part 2: correlation between histological changes and nerve evoked contractions.

We determined the effect of pelvic organ decentralization and reinnervation 1 yr later on urinary bladder histology and function. Nineteen canines underwent decentralization by bilateral transection of all coccygeal and sacral (S) spinal roots, dorsal roots of lumbar (L)7, and hypogastric nerves. After exclusions, eight were reinnervated 12 mo postdecentralization with obturator-to-pelvic and sciatic-to-pudendal nerve transfers, then euthanized 8-12 mo later.

Force dependent effects of chronic overuse on fibrosis-related genes and proteins in skeletal muscles.

Aim: To examine the chronic effect of force on mRNA and protein expression levels of fibrosis-related genes in flexor digitorum muscles in a rat model of repetitive overuse injury that induces muscle fibrosis at high force levels.

Materials And Methods: Two groups of rats were trained to perform a voluntary repetitive lever-pulling task at either a high (HFHR) or a low force (LFHR) for 18 weeks, while a control group (FRC) performed no task. RNA and protein were prepared from forelimb flexor digitorum muscles.

Blocking CCN2 preferentially inhibits osteoclastogenesis induced by repetitive high force bone loading.

: We recently found that blocking CCN2 signaling using a monoclonal antibody (FG-3019) may be a novel therapeutic strategy for reducing overuse-induced tissue fibrosis. Since CCN2 plays roles in osteoclastogenesis, and persistent performance of a high repetition high force (HRHF) lever pulling task results in a loss in trabecular bone volume in the radius, we examined here whether blocking CCN2 signaling would reduce the early catabolic effects of performing a HRHF task for 3 weeks. : Young adult, female, Sprague-Dawley rats were operantly shaped to learn to pull at high force levels, before performing the HRHF task for 3 weeks.

Blocking CTGF/CCN2 reverses neural fibrosis and sensorimotor declines in a rat model of overuse-induced median mononeuropathy.

Encapsulation of median nerves is a hallmark of overuse-induced median mononeuropathy and contributes to functional declines. We tested if an antibody against CTGF/CCN2 (termed FG-3019 or Pamrevlumab) reduces established neural fibrosis and sensorimotor declines in a clinically relevant rodent model of overuse in which median mononeuropathy develops. Young adult female rats performed a high repetition high force (HRHF) lever-pulling task for 18 weeks.

Blocking CTGF/CCN2 reduces established skeletal muscle fibrosis in a rat model of overuse injury.

Tissue fibrosis is a hallmark of overuse musculoskeletal injuries and contributes to functional declines. We tested whether inhibition of CCN2 (cellular communication network factor 2, previously known as connective tissue growth factor, CTGF) using a specific antibody (termed FG-3019 or pamrevlumab) reduces established overuse-induced muscle fibrosis in a clinically relevant rodent model of upper extremity overuse injury. Young adult rats performed a high repetition high force (HRHF) reaching and lever-pulling task for 18 weeks, after first being shaped for 6 weeks to learn this operant task.

Forced treadmill running reduces systemic inflammation yet worsens upper limb discomfort in a rat model of work-related musculoskeletal disorders.

Background: Musculoskeletal disorders can result from prolonged repetitive and/or forceful movements. Performance of an upper extremity high repetition high force task increases serum pro-inflammatory cytokines and upper extremity sensorimotor declines in a rat model of work-related musculoskeletal disorders. Since one of the most efficacious treatments for musculoskeletal pain is exercise, this study investigated the effectiveness of treadmill running in preventing these responses.

Comparing effects of rest with or without a NK1RA on fibrosis and sensorimotor declines induced by a voluntary moderate demand task.

Objectives: Fibrosis is one contributing factor in motor dysfunction and discomfort in patients with overuse musculoskeletal disorders. We pharmacologically targeted the primary receptor for Substance P, neurokinin-1, using a specific antagonist (NK1RA) in a rat model of overuse with the goal of improving tissue fibrosis and discomfort.

Methods: Female rats performed a low repetition, high force (LRHF) grasping task for 12 weeks, or performed the task for 12 weeks before being placed on a four week rest break, with or without simultaneous NK1RA treatment.

Role of Magnetic Resonance Imaging in Classifying Individuals Who Will Develop Accelerated Radiographic Knee Osteoarthritis.

We assessed whether adding magnetic resonance (MR)-based features to a base model of clinically accessible participant characteristics (i.e., serological, radiographic, demographic, symptoms, and physical function) improved classification of adults who developed accelerated radiographic knee osteoarthritis (AKOA) or not over the subsequent 4 years.

Blocking CCN2 Reduces Progression of Sensorimotor Declines and Fibrosis in a Rat Model of Chronic Repetitive Overuse.

Fibrosis may be a key factor in sensorimotor dysfunction in patients with chronic overuse-induced musculoskeletal disorders. Using a clinically relevant rodent model, in which performance of a high demand handle-pulling task induces tissue fibrosis and sensorimotor declines, we pharmacologically blocked cellular communication network factor 2 (CCN2; connective tissue growth factor) with the goal of reducing the progression of these changes. Young adult, female Sprague-Dawley rats were shaped to learn to pull at high force levels (10 min/day, 5 weeks), before performing a high repetition high force (HRHF) task for 3 weeks (2 h/day, 3 days/week).

Manual therapy prevents onset of nociceptor activity, sensorimotor dysfunction, and neural fibrosis induced by a volitional repetitive task.

Painful and disabling musculoskeletal disorders remain prevalent. In rats trained to perform repetitive tasks leading to signs and dysfunction similar to those in humans, we tested whether manual therapy would prevent the development of the pathologies and symptoms. We collected behavioral, electrophysiological, and histological data from control rats, rats that trained for 5 weeks before performing a high-repetition high-force (HRHF) task for 3 weeks untreated, and trained rats that performed the task for 3 weeks while being treated 3x/week using modeled manual therapy (MMT) to the forearm (HRHF + MMT).

Prolonged high force high repetition pulling induces osteocyte apoptosis and trabecular bone loss in distal radius, while low force high repetition pulling induces bone anabolism.

We have an operant rat model of upper extremity reaching and grasping in which we examined the impact of performing a high force high repetition (High-ForceHR) versus a low force low repetition (Low-ForceHR) task for 18weeks on the radius and ulna, compared to age-matched controls. High-ForceHR rats performed at 4 reaches/min and 50% of their maximum voluntary pulling force for 2h/day, 3days/week. Low-ForceHR rats performed at 6% maximum voluntary pulling force.

Inflammation and glucose homeostasis are associated with specific structural features among adults without knee osteoarthritis: a cross-sectional study from the osteoarthritis initiative.

Background: Greater age and body mass index are strong risk factors for osteoarthritis (OA). Older and overweight individuals may be more susceptible to OA because these factors alter tissue turnover in menisci, articular cartilage, and bone via altered glucose homeostasis and inflammation. Understanding the role of inflammation and glucose homeostasis on structural features of early-stage OA may help identify therapeutic targets to delay or prevent the onset of OA among subsets of adults with these features.

Risk factors can classify individuals who develop accelerated knee osteoarthritis: Data from the osteoarthritis initiative.

We assessed which combinations of risk factors can classify adults who develop accelerated knee osteoarthritis (KOA) or not and which factors are most important. We conducted a case-control study using data from baseline and the first four annual visits of the Osteoarthritis Initiative. Participants had no radiographic KOA at baseline (Kellgren-Lawrence [KL]<2).

Preliminary Model for the Design of a Custom Middle Ear Prosthesis.

Hypothesis: Custom prostheses could be used to recreate the ossicular chain and improve hearing.

Background: Ossicular discontinuity or fixation occurs in 55% of cases of conductive hearing loss, with most cases involving the incus. Reconstruction has been achieved by a variety of methods; however, there has been little improvement in hearing outcomes in decades.

Substance P increases CCN2 dependent on TGF-beta yet Collagen Type I via TGF-beta1 dependent and independent pathways in tenocytes.

Transforming growth factor beta 1 (TGFbeta-1) and connective tissue growth factor (CCN2) are important mediators of tissue repair and fibrosis, with CCN2 functioning as a downstream mediator of TGFβ-1. Substance P (SP) is also linked to collagen production in tenocytes. A link between SP, TGFbeta-1 and CCN2 has yet to be established in tenocytes or fibrogenic processes.

Glucose homeostasis influences the risk of incident knee osteoarthritis: Data from the osteoarthritis initiative.

We aimed to determine if serum measures of impaired glucose homeostasis (glucose concentrations or glycated serum protein, GSP) or systemic inflammation (high-sensitivity C-reactive protein, CRP) are related to incident typical knee osteoarthritis (KOA) or incident accelerated KOA. We conducted a case-control study using the Osteoarthritis Initiative's baseline and first four annual visits. All participants had no radiographic KOA at baseline (Kellgren-Lawrence [KL] < 2).