CGRP fibers sprout within gastrocnemius muscle following complete spinal cord injury in rodents.

Following spinal cord injury nociceptive afferents exhibit functional and anatomical plasticity within the spinal dorsal horn. This plasticity is, at least in part, maladaptive, contributing to secondary complications related to neuropathic pain, autonomic dysreflexia, and spasticity. While previous studies have shown that nociceptors, particularly CGRP C-fibers, are also capable of sprouting peripherally following pathologies of chronic inflammation, muscle disuse, and denervation, the peripheral plasticity of C-fibers following spinal cord injury remains largely uninvestigated.

Systematic Search and Modified e-Delphi Consensus for Serum Bone Biomarkers in Humans and Animal Models with SCI: Methodology.

Introduction: Alterations to bone metabolism deteriorations in bone density and architecture after spinal cord injury (SCI) are complex and multifactorial: mechanical unloading, impaired osteoblast activity, altered hormone levels, and regional blood flow combine to increase lower extremity fracture incidence and mortality. Bone biomarkers are vital to detect disease, identify candidate therapies, monitor therapy effectiveness, and quantify fracture risk.

Objectives: This study aimed to synthesize available literature on serum and plasma bone biomarkers in both animal and human SCI models and to generate consensus regarding their appropriateness for use across the translational continuum.

Cardiovascular and Locomotor Recovery Following Hindlimb Muscle Stretching of Rodents with a Clinically Relevant Model of Spinal Cord Injury.

Physical therapy stretching remains one of the most prevalent therapies for patients with spinal cord injury (SCI); however, we have previously shown that daily hindlimb muscle stretching of rats following a T10 SCI significantly disrupts their hindlimb locomotor function, likely through maladaptive sprouting of nociceptive afferents and modulation of lumbar spinal circuitry. Despite these clinically significant findings, mid-thoracic contusion models do not represent a majority of clinical injuries and are not effective for modeling the loss of cardiovascular control and autonomic complications that patients with higher level SCI experience. Therefore, the objective of the current study was to examine the effects of hindlimb stretching on the locomotor and cardiovascular function of rats with a T2 SCI.

Reorganization of spinal neural connectivity following recovery after thoracic spinal cord injury: insights from computational modelling.

Rats exhibit significant recovery of locomotor function following incomplete spinal cord injuries, albeit with altered gait expression and reduced speed and stepping frequency. These changes likely result from and give insight into the reorganization within spared and injured spinal circuitry. Previously, we developed computational models of the mouse spinal locomotor circuitry controlling speed-dependent gait expression (Danner et al.

Safety and Feasibility of Early Activity-Based Therapy Following Severe Traumatic Spinal Cord Injury: Results from a Single-Arm Pilot Trial.

Early activity-based therapy (E-ABT) has the potential to decrease complications and radically improve neurofunctional recovery following traumatic spinal cord injury (TSCI). Unfortunately, E-ABT after TSCI has never been attempted in humans due to practical obstacles and potential safety concerns. This study aims to report on the safety and feasibility outcomes of the Protocol for Rapid Onset of Mobilization in Patients with Traumatic SCI (PROMPT-SCI) trial: the first-ever trial of E-ABT in critically ill patients who suffered a severe TSCI.

Combining clinically common drugs with hindlimb stretching in spinal cord injured rodents.

Study Design: Preclinical pilot study.

Objectives: To explore peripheral and central nociceptive mechanisms that contribute to muscle stretch-induced locomotor deficits following spinal cord injury.

Setting: Kentucky Spinal Cord Injury Research Center, Louisville, KY, USA.

Claims-Based Algorithm to Identify Pre-Exposure Prophylaxis Indications for Tenofovir Disoproxil Fumarate and Emtricitabine Prescriptions (2012-2014): Validation Study.

Background: To monitor the use of tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) and related medicines for pre-exposure prophylaxis (PrEP) as HIV prevention using commercial pharmacy data, it is necessary to determine whether TDF/FTC prescriptions are used for PrEP or for some other clinical indication.

Objective: This study aimed to validate an algorithm to distinguish the use of TDF/FTC for HIV prevention or infectious disease treatment.

Methods: An algorithm was developed to identify whether TDF/FTC prescriptions were for PrEP or for other indications from large-scale administrative databases.

Data Safety Monitoring Boards: Overview of Structure and Role in Spinal Cord Injury Studies.

This paper provides an overview of the history, composition, organization, responsibilities, and regulatory requirements of Data Safety Monitoring Boards (DSMB), with particular reference to the context of clinical trials in spinal cord injury. It is intended to help potential members of such boards and those undertaking the design of new clinical trials to understand the important role of the DSMB in safeguarding the integrity of complex trials, promoting safety, and countering potential bias. An independent DSMB helps to protect research subjects by providing study oversight and serves as an additional step to assure that clinical trials are performed to existing and appropriate standards.

Silencing long-descending inter-enlargement propriospinal neurons improves hindlimb stepping after contusive spinal cord injuries.

Spinal locomotor circuitry is comprised of rhythm generating centers, one for each limb, that are interconnected by local and long-distance propriospinal neurons thought to carry temporal information necessary for interlimb coordination and gait control. We showed previously that conditional silencing of the long ascending propriospinal neurons (LAPNs) that project from the lumbar to the cervical rhythmogenic centers (L1/L2 to C6), disrupts right-left alternation of both the forelimbs and hindlimbs without significantly disrupting other fundamental aspects of interlimb and speed-dependent coordination (Pocratsky et al., 2020).

Long ascending propriospinal neurons are heterogenous and subject to spinal cord injury induced anatomic plasticity.

Long ascending propriospinal neurons (LAPNs) are a subset of spinal interneurons that provide direct connectivity between distant spinal segments. Here, we focus specifically on an anatomically defined population of "inter-enlargement" LAPNs with cell bodies at L2/3 and terminals at C5/6. Previous studies showed that silencing LAPNs in awake and freely moving animals disrupted interlimb coordination of the hindlimbs, forelimbs, and heterolateral limb pairs.

Construction of a Searchable Database for Gene Expression Changes in Spinal Cord Injury Experiments.

Spinal cord injury (SCI) is a debilitating condition with an estimated 18,000 new cases annually in the United States. The field has accepted and adopted standardized databases such as the Open Data Commons for Spinal Cord Injury (ODC-SCI) to aid in broader analyses, but these currently lack high-throughput data despite the availability of nearly 6000 samples from over 90 studies available in the Sequence Read Archive. This limits the potential for large datasets to enhance our understanding of SCI-related mechanisms at the molecular and cellular level.

Spinal control of locomotion before and after spinal cord injury.

Thoracic spinal cord injury affects long propriospinal neurons that interconnect the cervical and lumbar enlargements. These neurons are crucial for coordinating forelimb and hindlimb locomotor movements in a speed-dependent manner. However, recovery from spinal cord injury is usually studied over a very limited range of speeds that may not fully expose circuitry dysfunction.

Construction of a searchable database for gene expression changes in spinal cord injury experiments.

Spinal cord injury (SCI) is a debilitating disease resulting in an estimated 18,000 new cases in the United States on an annual basis. Significant behavioral research on animal models has led to a large amount of data, some of which has been catalogued in the Open Data Commons for Spinal Cord Injury (ODC-SCI). More recently, high throughput sequencing experiments have been utilized to understand molecular mechanisms associated with SCI, with nearly 6,000 samples from over 90 studies available in the Sequence Read Archive.

Unintentional Effects from Housing Enhancement Resulting in Functional Improvement in Spinal Cord-Injured Mice.

It is well established that both positive and negative housing conditions of laboratory animals can affect behavioral, biochemical, and physiological responses. Housing enhancements have been shown to have beneficial effects on locomotor outcomes in rodents with spinal cord injury (SCI). Subsequent to an unplanned housing enhancement of the addition of a balcony to home cages by animal care personnel at a research facility, a retrospective analysis of multiple SCI studies was performed to determine whether outcomes differed before (four studies,  = 28) and after (four studies,  = 23) the addition of the balcony.

Direct Ryanodine Receptor-2 Knockout in Primary Afferent Fibers Modestly Affects Neurological Recovery after Contusive Spinal Cord Injury.

Neuronal ryanodine receptors (RyR) release calcium from internal stores and play a key role in synaptic plasticity, learning, and memory. Dysregulation of RyR function contributes to neurodegeneration and negatively impacts neurological recovery after spinal cord injury (SCI). However, the individual role of RyR isoforms and the underlying mechanisms remain poorly understood.

The use of alkaline phosphatase as a bone turnover marker after spinal cord injury: A scoping review of human and animal studies.

Background: Serum alkaline phosphatase (ALP) is measured as an indicator of bone or liver disease. Bone-specific alkaline phosphatase (B-ALP) is an isoform of ALP found in the bone tissue which can predict fractures and heterotopic ossification.

Objective: The aim of this scoping review was to explore the current use of ALP and B-ALP in studies using humans or animal models of SCI, and to identify ways to advance future research using ALP and B-ALP as a bone marker after SCI.

Silencing long ascending propriospinal neurons after spinal cord injury improves hindlimb stepping in the adult rat.

Long ascending propriospinal neurons (LAPNs) are a subpopulation of spinal cord interneurons that directly connect the lumbar and cervical enlargements. Previously we showed, in uninjured animals, that conditionally silencing LAPNs disrupted left-right coordination of the hindlimbs and forelimbs in a context-dependent manner, demonstrating that LAPNs secure alternation of the fore- and hindlimb pairs during overground stepping. Given the ventrolateral location of LAPN axons in the spinal cord white matter, many likely remain intact following incomplete, contusive, thoracic spinal cord injury (SCI), suggesting a potential role in the recovery of stepping.

Protocol for rapid onset of mobilisation in patients with traumatic spinal cord injury (PROMPT-SCI) study: a single-arm proof-of-concept trial of early in-bed leg cycling following acute traumatic spinal cord injury.

Introduction: Activity-based therapy (ABT) is an important aspect of rehabilitation following traumatic spinal cord injury (SCI). Unfortunately, it has never been adapted to acute care despite compelling preclinical evidence showing that it is safe and effective for promoting neurological recovery when started within days after SCI. This article provides the protocol for a study that will determine the feasibility and explore potential benefits of early ABT in the form of in-bed leg cycling initiated within 48 hours after the end of spinal surgery for SCI.

Markers of susceptibility to cardiac arrhythmia in experimental spinal cord injury and the impact of sympathetic stimulation and exercise training.

Injury to descending autonomic (sympathetic) pathways is common after high-level spinal cord injury (SCI) and associated with abnormal blood pressure and heart rate regulation. In individuals with high-level SCI, abnormal sympathovagal balance (such as during autonomic dysreflexia; paroxysmal hypertension provoked by sensory stimuli below the injury) is proarrhythmogenic. Exercise training is a key component of SCI rehabilitation and management of cardiovascular disease risk, but it is unclear whether exercise training influences susceptibility to cardiac arrhythmia.