Dena Howland

University of Louisville | UL · Department of Neurological Surgery and the KSCIRC

Purpose Postoperative pneumonia remains a common complication of surgery, despite increased attention. The purpose of our study was to determine the effects of routine surgery and post-surgical opioid administration on airway protection risk. Methods Eight healthy adult cats were evaluated to determine changes in airway protection status and for e...

Background Spinal cord injury (SCI) affects locomotion and quality of life. Two spinal cord stimulation approaches are currently under investigation for restoring standing and walking following SCI: epidural spinal cord stimulation (ESCS) and intraspinal microstimulation (ISMS). In ESCS, electrodes are placed on the dura mater and in ISMS, ultrafin...

Objective Postoperative pneumonia remains a common complication of surgery, despite increased attention. The purpose of our study was to determine the effects of routine surgery and post-surgical opioid administration on airway protection risk. Methods Eight healthy adult cats were evaluated for dysphagia in 2 experiments. 1) In 4 female cats airw...

Gastrointestinal (GI) complications, including motility disorders, metabolic deficiencies, and changes in gut microbiota following spinal cord injury (SCI), are associated with poor outcomes. After SCI, the autonomic nervous system becomes unbalanced below the level of injury and can lead to severe GI dysfunction. The SmartPill™ is a non-invasive c...

The immature central nervous system is recognized as having substantial neuroplastic capacity. In this study, we explored the hypothesis that rehabilitation can exploit that potential and elicit reciprocal walking in nonambulatory children with chronic, severe (i.e., lower extremity motor score < 10/50) spinal cord injuries (SCIs). Seven male subje...

Animal models are necessary to identify pathological changes and help assess therapeutic outcomes following spinal cord injury (SCI). Small animal models offer value in research in terms of their easily managed size, minimal maintenance requirements, lower cost, well-characterized genomes, and ability to power research studies. However, despite the...

Laryngeal function is vital to airway protection. While swallow is mediated by the brainstem, mechanisms underlying increased risk of dysphagia after cervical spinal cord injury (SCI) are unknown. We hypothesized that loss of descending phrenic drive affects swallow and breathing differently, and loss of ascending spinal afferent information alters...

Proper function of the larynx is vital to airway protection, including swallow. While the swallow reflex is controlled by the brainstem, patients with cervical spinal cord injuries (cSCI) are likely at increased risk of disordered swallow (dysphagia) and pneumonia, and the underlying mechanisms are unknown. We aimed to determine if acute spinal cor...

Successful propagation throughout the step cycle is contingent on adequate regulation of whole-limb stiffness by proprioceptive feedback. Following spinal cord injury (SCI), there are changes in the strength and organization of proprioceptive feedback that can result in altered joint stiffness. In this study, we measured changes in autogenic feedba...

There is an increasing need to develop approaches that will not only improve the clinical management of neurogenic lower urinary tract dysfunction (NLUTD) after spinal cord injury (SCI), but also advance therapeutic interventions aimed at recovering bladder function. While preclinical research frequently employs rodent SCI models, large animals suc...

Yucatan miniature pigs (YMPs) are similar to humans in spinal cord size, physiological and neuroanatomical features, making them a useful model for human spinal cord injury. However, little is known regarding pig gait kinematics, especially on a treadmill. In this study, twelve healthy YMPs were assessed during bipedal and/or quadrupedal stepping o...

Lung volume is modulated by sensory afferent feedback via vagal and spinal pathways. The purpose of this study was to systematically alter afferent feedback with and without a mechanical challenge (chest compression). We hypothesized that manipulation of afferent feedback by nebulization of lidocaine, extra-thoracic vagotomy, or lidocaine administr...

Swallow-breathing coordination is influenced by changes in lung volume, which is modulated by feedback from both vagal and spinal sensory afferents. The purpose of this study was to manipulate feedback from these afferents, with and without a simultaneous mechanical challenge (chest compression), in order to assess the influence of each sensory pat...

Inhibitory pathways from Golgi tendon organs project widely between muscles crossing different joints and axes of rotation. Evidence suggests that the strength and distribution of this intermuscular inhibition is dependent on motor task and corresponding signals from the brainstem. The purpose of the present study was to investigate whether this se...

Afferent feedback can appreciably alter the pharyngeal phase of swallow. In order to measure the stability of the swallow motor pattern during several types of alterations in afferent feedback, we assessed swallow during a conventional water challenge in four anesthetized cats, and compared that to swallows induced by fixed (20 Hz) and stochastic (...

Laryngeal dysfunction is a common symptom following cervical spinal cord injury (cSCI) and currently there are no effective pharmacological interventions or behavioral treatments. The larynx is the primary valve controlling entrance into the trachea and lungs via opening and closing of the vocal folds. Although not well studied following cSCI, it i...

Cervical spinal cord injuries (cSCIs) can cause swallow disorder (dysphagia), potentially resulting in aspiration and pneumonia. Dysphagia is characterized by disruption of the swallow motor pattern, which involves sequential activation of muscles that propels the bolus into the esophagus while avoiding the airway. Normal swallow includes diaphragm...

Background Kinematic and kinetic analysis have been used to gain an understanding of canine movement and joint loading during gait. By non-invasively predicting muscle activation patterns and forces during gait, musculoskeletal models can further our understanding of normal variability and muscle activation patterns and force profiles characteristi...

Transfer of information across a spinal lesion is required for many aspects of recovery across diverse motor systems. Our understanding of axonal plasticity, and which subpopulations of neurons may contribute to bridging substrates following injury, however, remains relatively incomplete. Most recently, attention has been directed to propriospinal...

Swallow disorder (dysphagia) can cause aspiration and lead to pneumonia in a number of patient populations, including individuals with cervical spinal cord injury. Dysphagia is characterized by dysfunction in the swallow motor pattern, which is a sequential activation of muscles that propels the bolus into the esophagus and prevents entry into the...

Muscle position feedback, via receptors for stretch (muscle spindles) and force (golgi tendon organs), is critical for the muscular coordination and proprioception that is essential for most movements. Muscle spindles are innervated by gamma motoneurons that modulate their sensitivity to stretch. Recent reports suggest that 5‐HT 1D receptors can mo...

Anatomical connections are reported between the cerebellum and brainstem nuclei involved in swallow such as the nucleus tractus solitarius, nucleus ambiguus, and Kölliker-fuse nuclei. Despite these connections, a functional role of the cerebellum during swallow has not been elucidated. Therefore, we examined the effects of cerebellectomy on swallow...

Spinal cord injury (SCI) can amplify and redistribute intermuscular inhibitory force feedback (iFFB) from Golgi tendon organs and release clasp-knife inhibition (CKI), a powerful inhibition arising from group III and IV muscle receptors. The CKI can be evoked experimentally by transecting the dorsal spinal cord, and the reorganization of iFFB can b...

The effects of cervical hemisection on swallow have not been determined. We hypothesized that cervical hemisection would increase swallow excitability and shift the pattern of swallow breathing coordination to maintain pharyngeal clearance. Electromyograms of the mylohyoid, geniohyoid, thyrohyoid, thyroarytenoid, thyropharyngeus, cricopharyngeus an...

Action of the diaphragm is necessary for negative force production during breathing and cough. However, the effect of cervical spinal cord injury on action of the diaphragm during cough is not known. It was hypothesized that C2 hemisection would result in a loss of cough excitability and depression of the diaphragm during breathing and cough. Elect...

Background Kinematic gait analysis is an important noninvasive technique used for quantitative evaluation and description of locomotion and other movements in healthy and injured populations. Three dimensional (3D) kinematic analysis offers additional outcome measures including internal-external rotation not characterized using sagittal plane (2D)...

Background: Kinematic gait analysis is an important noninvasive technique used for quantitative evaluation and description of locomotion and other movements in healthy and injured populations. Three dimensional (3D) kinematic analysis offers additional outcome measures including internal-external rotation not characterized using sagittal plane anal...

Introduction Functional walking requires the ability to modify one’s gait pattern to environmental demands and task goals—gait adaptability. Following incomplete spinal cord injury (ISCI), gait rehabilitation such as locomotor training (Basic-LT) emphasizes intense, repetitive stepping practice. Rehabilitation approaches focusing on practice of gai...

It is well established that sensory feedback regulates the mechanical properties of limbs, particularly when the limbs interact with the environment. This is accomplished at a reflex level through length feedback from muscle spindle receptors and inhibitory force feedback from Golgi tendon organs. Briefly, length feedback from muscle spindle recept...

Devastating functional deficits following spinal cord injury (SCI) are no longer considered irreversible. Laboratory findings indicate that some improvements can be achieved with therapeutic approaches designed to promote tissue repair. It also has become widely recognised that the spinal cord is not a ‘hard‐wired’ structure; neural circuits can un...

We investigated the hypothesis, motivated in part by a coordinated computational cough network model, that second-order neurons in the nucleus tractus solitarius (NTS) act as a filter that shapes afferent input to the ventral respiratory network (VRC) during the production of cough. In vivo experiments were conducted on anesthetized spontaneously b...

Background: Fluorogold (FG) is used by many groups to retrogradely trace nervous system pathways. Fluorogold, while a robust tracer, also is neurotoxic and causes tissue damage at the injection site and leads to motor deficits. New method: In the current study, we describe a method for enhancing FG-uptake using Triton™ and an overall procedure f...

A module is a functional unit of the nervous system that specifies functionally-relevant patterns of muscle activation. In adults, 4-5 modules account for muscle activation during walking. Neurologic injury alters modular control and is associated with walking impairments. The effect of neurologic injury on modular control in children is unknown an...

The unscented Kalman filter (UKF) was recently introduced in literature for simultaneous multi-tensor estimation and tractography. This UKF however was not intrinsic to the space of diffusion tensors. Lack of this key property leads to inaccuracies in the multi-tensor estimation as well as in tractography. In this paper, we propose an novel intrins...

Advances in the neurobiology of spinal cord injury (SCI) have prompted increasing attention to opportunities for moving experimental strategies towards clinical applications. Preclinical studies are the centerpiece of the translational process. A major challenge is to establish strategies for achieving optimal translational progression while minimi...

Arm and leg coordination naturally emerges during walking, but can be affected by stroke or Parkinson's disease. The purpose of this preliminary study was to characterize arm and leg coordination during treadmill walking at self-selected comfortable walking speeds (CWSs) in individuals using arm swing with motor incomplete spinal cord injury (iSCI)...

Following a lateralized spinal cord injury (SCI) in humans, substantial walking recovery occurs; however, deficits persist in adaptive features of locomotion critical for community ambulation, including obstacle negotiation. Normal obstacle negotiation is accomplished by an increase in flexion during swing. If an object is unanticipated or supraspi...

Groupwise image registration is an essential part of atlas construction which is a very import and challenging task in medical image analysis. In this paper, we present a novel atlas construction technique using a groupwise registration of high angular resolution diffusion (MR) imaging datasets each of which is represented by a Gaussian Mixture fie...

A number of studies have shown that chondroitinase ABC (Ch'ase ABC) digestion of inhibitory chondroitin sulfate glycosaminoglycans significantly enhances axonal growth and recovery in rodents following spinal cord injury (SCI). Further, our group has shown improved recovery following SCI in the larger cat model. The purpose of the current study was...

Observational, cross-sectional study from a convenience sample with pretest/posttest data from a sample subset. Determine the presence of walking-related arm swing after spinal cord injury (SCI), its associated factors and whether arm swing may change after locomotor training (LT). Malcom Randall VAMC and University of Florida, Gainesville, FL. Arm...

A function of the abdominal expiratory muscles is the generation of cough, a critical respiratory defense mechanism that is often disrupted following spinal cord injury. We assessed the effects of a lateral T9/10 hemisection on cough production at 4, 13 and 21 weeks post-injury in cats receiving extensive locomotor training. The magnitudes of esoph...

The authors previously reported on walking recovery in a nonambulatory child with chronic, severe, incomplete cervical spinal cord injury (SCI) after 76 sessions of locomotor training (LT). Although clinical measures did not predict his recovery, reciprocal patterned leg movements developed, affording recovery of independent walking with a reverse...

Pulmonary morbidity is high following spinal cord injury and is due, in part, to impairment of airway protective behaviors. These airway protective behaviors include augmented breaths, the cough reflex, and expiration reflexes. Functional recovery of these behaviors has been reported after spinal cord injury. In humans, evidence for functional reco...

Functional deficits following spinal cord injury are no longer viewed as totally irreversible. Laboratory findings indicate the ability to walk can be partially restored by individual or combined therapeutic approaches targeting specific cellular responses to trauma. In addition, certain rehabilitation strategies can enhance ambulatory capacity, as...

In Diffusion Weighted Magnetic Resonance Image (DW-MRI) processing, a 2nd order tensor has been commonly used to approximate the diffusivity function at each lattice point of the DW-MRI data. From this tensor approximation, one can compute useful scalar quantities (e.g. anisotropy, mean diffusivity) which have been clinically used for monitoring en...

Poststroke reaching is characterized by excessive trunk motion and abnormal shoulder-elbow coordination. Little attention is typically given to arm-trunk kinematics during task practice. Preventing compensatory trunk motion during short-term practice immediately improves kinematics, but effects of longer-term practice are unknown. This study compar...

Locomotor training (LT) enhances walking in adult experimental animals and humans with mild-to-moderate spinal cord injuries (SCIs). The animal literature suggests that the effects of LT may be greater on an immature nervous system than on a mature nervous system. The purpose of this study was to evaluate the effects of LT in a child with chronic,...

This study investigated whether or not individuals with ataxia from stroke improve their upper extremity motor function with intense motor practice. Three individuals with ataxia from chronic stroke completed modified constraint-induced movement therapy (CIMT) protocols. Stroke Participants 1 and 2 completed 60 hours and Stroke Participant 3 comple...

In this paper we present a novel method for estimating a field of asymmetric spherical functions, dubbed tractosemas, given the intra-voxel displacement probability information. The peaks of tractosemas correspond to directions of distinct fibers, which can have either symmetric or asymmetric local fiber structure. This is in contrast to the existi...

Chondroitin sulfate proteoglycans (CSPGs) are upregulated in the central nervous system following injury. Chondroitin sulfate glycosaminoglycan (CS GAG) side chains substituted on this family of molecules contribute to the limited functional recovery following injury by restricting axonal growth and synaptic plasticity. In the current study, the ef...

Chondroitinase ABC (Ch'ase ABC) is a bacterial lyase that degrades chondroitin sulfate (CS), dermatan sulfate, and hyaluronan glycosaminoglycans (GAGs). This enzyme has received significant attention as a potential therapy for promoting central nervous system and peripheral nervous system repair based on its degradation of CS GAGs. Determination of...

Netrin-1 regulates axon extension during embryonic development and is expressed by neurons and myelinating oligodendrocytes in the adult CNS. To investigate the potential role of netrin-1 after spinal cord injury, we examined the expression of netrin-1 and netrin receptors after sagittal myelotomy in adult rats. This lesion targets spinal commissur...

Several lines of reasoning suggest that the phosphorylated axonal form of the neurofilament subunit NF-H is likely to be released from damaged and diseased neurons in significant amounts. Detection of this protein in serum or CSF might therefore provide information about the presence and degree of neuronal loss. We therefore developed a sensitive N...

Aggrecan is a chondroitin sulfate (CS)/keratan sulfate (KS)-substituted proteoglycan (PG) abundant in cartilage which is also present within the mammalian embryonic, adult, and injured adult central nervous system (CNS). Although its role within the CNS is not clear, cell culture studies show that when substituted with CS, aggrecan inhibits neurite...

Aggrecan is a large proteoglycan (PG) that has been grouped with different PG families on the basis of its physical characteristics. These families include the chondroitin sulfate PGs, which appear to inhibit the migration of cells and axons during development. Although aggrecan has been studied primarily in cartilage, in the present study, tissue...

The pathological sequelae of spinal cord injury (SCI) are complex and generally result in chronic neuronal loss, axonal damage, and demyelination. Although there have been several experimental therapeutic approaches studied to repair the chronically injured spinal cord, one strategy that has shown considerable promise is fetal tissue grafting. Buil...

Extrinsic factors appear to contribute to the lack of regeneration in the injured adult spinal cord. It is likely that these extrinsic factors include a group of putative growth inhibitory molecules known as chondroitin sulfate proteoglycans (CSPGs). The aims of this study were to determine: (1) the consequences of spinal cord contusion injury on C...

Solid or suspension grafts of fetal spinal cord (FSC), caudal brainstem (FBSt), neocortex (FNCx) or a combination of either FSC/FNCx or FSC/FBSt were placed into cavities produced by static loading (i.e., compression) of the spinal cord of adult cats two to 30 weeks after injury. Extensively vascularized, viable graft tissue was found in all animal...

The development of bipedal treadmill locomotion and overground locomotion has previously been studied in the kitten; the development of quadrupedal treadmill locomotion has not. We evaluated and compared all three forms of locomotion in the normal kitten and present quantitative data comparing the development of quadrupedal treadmill and overground...

This study was undertaken to determine the locomotor capability of kittens whose spinal cords were transected at birth. The postnatal development of reflex and goal-directed locomotion was examined during the first 5 postnatal months in kittens that received low thoracic spinal cord transections as newborns. Some spinal kittens developed aberrant q...

We have studied the locomotor development of kittens that received complete low thoracic spinal cord transections and embryonic spinal cord transplants as newborns. Embryonic spinal cord (E21-E26) transplanted into the site of a transection integrated well with the host spinal cord and promoted the development of overground locomotion. Spinalized k...

It is well established that fetal neural tissue placed into acute lesions in both the newborn and adult rat spinal cord undergoes extensive differentiation and survives for extended periods (Bregman and Reier, 1986; Das, 1983a; Gelderd and Quarles, 1990; Himes et al., 1994; Jakeman and Reier, 1989; Nornes et al., 1983; Nothias and Pechanski, 1990;...

There has been much research studying the effect of homotypic embryonic neural tissue transplantation in the central nervous system of rats and cats, with promising results. The benefits of transplantation are dependent upon the appropriate aged donor. Therefore, it is critical that the exact age of the embryonic tissue be known. For this reason we...

Typescript. Thesis (Ph. D.)--Medical College of Pennsylvania, 1994. Includes bibliographical references (leaves 207-242).