Objectives. Electrical stimulation of the dorsal aspect of the upper thoracic spinal cord is used increasingly to treat patients with angina pectoris refractory to conventional therapeutic strategies. The purpose of this study was to determine whether spinal cord stimulation (SCS) in dogs affects regional myocardial blood flow and left-ventricular (LV) function before and during transient obstruction of the left anterior descending coronary artery (LAD). Methods. In anesthetized dogs, regional myocardial blood flow distribution was determined using radiolabeled microspheres and left-ventricular function was measured by impedance-derived pressure-volume loops. SCS was accomplished by stimulating the dorsal T1-T2 segments of the spinal cord using epidural bipolar electrodes at 90% of motor threshold (MT) (50 Hz, 0.2-ms duration). Effects of 5-min SCS were assessed under basal conditions and during 4-min occlusion of the LAD. Results. SCS alone evoked no change in regional myocardial blood flow or cardiovascular indices. Transient LAD occlusion significantly diminished blood flow within ischemic, but not in non-ischemic myocardial tissue. Left ventricular pressure-volume loops were shifted rightward during LAD occlusion. Cardiac indices were altered similarly during LAD occlusion and concurrent SCS. Conclusions. SCS does not influence the distribution of blood flow within the non-ischemic or ischemic myocardium. Nor does it modify LV pressure-volume dynamics in the anesthetized experimental preparation.

The South African Professional Board for Emergency Care prehospital Clinical Practice Guideline (CPG) recommends that emergency medical services (EMS) make use of the National Emergency X Radiography Utilization Study (NEXUS) rule and Canadian C-spine Rule (CCSR) when managing traumatic spinal injury. However, the safety and effectiveness of prehospital clinical spinal clearance or spinal motion restriction (SMR) decision support tools within poorly resourced settings are unclear. We conducted a scoping review on clinical spinal clearance and selective SMR decision support tools which aimed at identifying possible barriers to their implementation, safety, and effectiveness when used by EMS personnel. Studies were included if they described the use of clinical spinal clearance or SMR decision tools in first line management of blunt trauma patients by medical practitioners in the Emergency Department (ED) or by EMS personnel working in a prehospital setting. After screening, 42 documents fulfilled the inclusion criteria. Several selective SMR decision support tools have been implemented in the prehospital setting, the most common of which were those based on the NEXUS and the CCSR tools. Only one study evaluated the safety and efficacy of the NEXUS rule when used by EMS personnel. The limited prehospital literature available investigating either the NEXUS rule or CCSR therefore makes it difficult to determine its appropriateness for adoption and implementation by EMS personnel in other prehospital settings such as that of South Africa. Furthermore, commonly found prehospital NEXUS-based decision tools presented with unique challenges related to the subjective nature of some of the individual components of the decision tool. This leaves the decision tool open to interpretation by examiners and is especially relevant in settings, such as South Africa, where there are many different levels in scope of practices. This increases the risk of the patient being either under-triaged or over-triaged. More studies are therefore needed to definitively assess for the safety, efficacy and effectiveness of clinical spine clearance within the prehospital setting. It is believed that a selective SMR decision tool which has more specific instructions for the prehospital practitioner may be able to accommodate such challenges and is an area which needs further investigation.

Over 260,000 Americans are living with a traumatic spinal cord injury (SCI). Medical advances have increased the longevity of individuals living with SCI into middle age and beyond. The majority of these individuals are living with an incomplete SCI (NSCISC, 2012), and the proportion of incomplete injuries is rising (DeVivo, 2012). There is little research that specifically examines the changes in physical function experienced by individuals aging with a traumatic incomplete SCI. The purpose of this qualitative descriptive study was to describe the changes in physical function experienced by participants with a traumatic incomplete SCI aging through middle age. Data were collected through moderately structured individual interviews (N=17), in either a face-to-face (n=6) or an email (n=11) format. The seventeen participants ranged in age from 35 to 65 years, with a 16 to 36 year duration of injury. Participants described changes in various body systems and recalled the timing of those changes as they transitioned through their middle years. Qualitative content analysis revealed that participants described primarily gradual changes including decreased muscle strength, decreased endurance, weight gain, and wear and tear changes. When asked to identify sources of information about physical changes, participants predominantly emphasized their lack of knowledge about anticipated changes. Further content analysis revealed three themes related to this transition. Participants likened their experience to travelling through uncharted territory. They described strategies for living in uncharted territory that help them to prevent or manage changes in physical function, with sub-themes of being vigilant in their self-assessment and self-management practices, investing time in figuring out what changes they experienced and why those changes happened, and staying positive. They also described the importance of recognizing the impact of changes. These findings provide a foundation for understanding this age-related transition, and identify the need for further research to support effective self-management strategies and efficient mechanisms for disseminating this knowledge to people with SCI, their caregivers and families. In acute and chronic patient care settings, nurses are well-positioned to be a valuable support and information source for individuals living with an incomplete SCI.

Background: Spinal cord injury (SCI) is a devastating condition for which current treatment strategies provide no cure. Delivery of growth factors at the injury site may stimulate endogenous stem cells for nerve regeneration. Biocellulose (BC) was reported to be biocompatible, abundant and have adjustable mechanical properties. However, BC has not been tested for the treatment of SCI. Hypothesis: Composite microsphere loaded BC tubes can have a sustained protein release profile with high encapsulation efficiency and low initial burst rendering it suitable for spinal cord regeneration. Methods: Bovine serum albumin loaded poly (lactic-co-glycolic acid) microspheres were fabricated and characterized while studying the effect of different process parameters on encapsulation efficiency, release profile and morphology. Microspheres were loaded to BC tubes and were characterized morphologically and mechanically. Results: Inner phase volume and the drug:polymer ratio are the main factors impacting microsphere protein encapsulation. Furthermore, presence of different osmotic agent concentrations in the aqueous phase produced a smooth morphology while eliminating the initial burst. Finally, the composite BC tubes were fabricated, and mechanical properties were suitable for SCI applications. Contexte : Les lésions de la moelle épinière sont une maladie dévastatrice que les stratégies de traitement actuelles ne permettent pas de guérir. L'administration de facteurs de croissance sur le site de la lésion peut stimuler les cellules souches endogènes pour la régénération des nerfs. La biocellulose est biocompatible, abondante et possède des propriétés mécaniques ajustables. Cependant, la biocellulose n'a pas été testée pour le traitement des lésions de la moelle épinière. Hypothèse : Les microsphères en composite situées dans les tubes de biocellulose peuvent avoir un profil de libération soutenue de protéines avec une grande efficacité d'encapsulation ainsi qu’un faible taux de libération initial, ce qui les rend appropriés pour la régénération de la moelle épinière. Méthodes : Des microsphères de poly (acide lactique-co-glycolique) chargées d’albumine de sérum bovin ont été fabriquées et caractérisées tout en étudiant l'effet de différents paramètres du processus sur l'efficacité de l'encapsulation, le profil de libération et la morphologie. Les microsphères ont été mises dans des tubes de biocellulose et ont été entièrement caractérisées. Résultats : Le volume de la phase interne et le ratio médicament : polymère sont les principaux facteurs qui influent sur l'encapsulation des protéines en microsphères. De plus, la présence de différentes concentrations de sel dans la phase aqueuse a produit une morphologie lisse tout en éliminant la libération initiale. Enfin, les tubes de biocellulose en composite ont été fabriqués et les propriétés mécaniques étaient adaptées pour l’application sur des lésions de la moelle épinière.

Indiana University-Purdue University Indianapolis (IUPUI) / Spinal cord injury (SCI) is devastating and debilitating, and currently no effective treatments exist. Approximately, 12,000 new cases of SCI occur annually in the United States alone. The central nervous system has very low repair capability after injury, due to the toxic environment in the injured tissue. After spinal cord trauma, ruptured blood vessels cause neighboring cells and tissues to be deprived of oxygen and nutrients, and result in the accumulation of carbon dioxide and waste. New blood vessels form spontaneously after SCI, but then retract as the injured tissue forms a cavity. Thus, the newly formed vasculature likely retracts because it lacks a structural support matrix to extend across the lesion. Currently, in the field of spinal cord injury, combinational treatment approaches appear to hold the greatest therapeutic potential. Therefore, the aim of these studies was to transplant a novel, non-immunogenic, bioengineered hydrogel, into the injured spinal cord to serve as both a structural scaffold (for blood vessels, axons, and astrocytic processes), as well as a functional matrix with a time-controlled release of growth factors (Vascular endothelial growth factor, VEGF; Glial cell line-derived neurotrophic factor, GDNF). The benefit of this hydrogel is that it remains liquid at cooler temperatures, gels to conform to the space surrounding it at body temperature, and was designed to have a similar tensile strength as spinal cord tissue. This is advantageous due to the non-uniformity of lesion cavities following contusive spinal cord injury. Hydrogel alone and combinational treatment groups significantly improved several measures of functional recovery and showed modest histological improvements, yet did not provoke any increased sensitivity to a thermal stimulus. Collectively, these findings suggest that with further investigation, hydrogel along with a combination of growth factors might be a useful therapeutic approach for repairing the injured spinal cord.

Indiana University-Purdue University Indianapolis (IUPUI) / The vascular network highly coordinates with the central nervous system (CNS) on exchanging oxygen, nutrients and information transfer. The resemblance of the two systems at anatomical, cellular, and molecular levels also demonstrates their interdependence. The spinal cord is an integrated part of the CNS. Traumatic spinal cord injury (SCI) causes rapid systemic vascular responses and local neural tissue damage at the initial phase. The early disruption of the spinal vasculature breaks the supply-and-demand balance and facilitates the deterioration of the spinal cord tissue and functional deficits. Therefore, it is important to dissect the mechanism underlying vascular injury-mediated histological and functional consequences in order to develop potential therapeutic strategies. To visualize dynamic vascular changes after an acute SCI, a novel duo-color in vivo imaging technique was successfully developed in adult rats at the cervical level. This technique overcomes previous technical hurdles allowing real-time observation of vascular changes in live animals. Correlated with histological measures, in vivo vascular outcomes revealed a temporospatial relationship with neuronal and axonal loss, myelin disruption, inflammation, and glial responses. For the first time, we defined a “transitional zone” where significant blood vessel dilation and vascular leakage were observed simultaneously with vascular changes occurred at the injury epicenter acutely after SCI. These vascular changes at the transitional zone happened before any other cellular damage after SCI, suggesting a time window to prevent further neuronal damage in this region. Targeting the observed vascular leakage can work as a proof of concept that early vascular dysfunction contributes to the secondary neural tissue damage. Indeed, intravenous delivery of ferulic acid conjugated with glycol chitosan (FA-GC) to the injured sites immediate after SCI resulted in reduced vascular leakage, ventral horn neuronal loss, and partial recovery of forelimb function following a clinically-relevant contusive SCI at the 7th cervical spinal cord level. In conclusion, this work elucidated a novel role and mechanism of early vascular damage in the “transitional zone” prior to the secondary damage of neural tissue in this region and provided a novel treatment strategy for early neuroprotection and functional recovery. / 2021-11-04

Surgical procedures of the brain and spine that require manipulation of, and near nervous structures, require unique considerations in their approach. Over the past 100 years, techniques have been developed and refined for localization of specific structures allowing for safer, more accurate interventions. These include the pre-operative use of Electroencephalography (EEG) in combination with radiographical imaging and intraoperative neurophysiological techniques rooted in electrophysiology. Since the introduction of EEG and electrical cortical stimulation, physicians have had the tools to diagnose neurological conditions while also being able to complete surgical interventions with a level of safety. By the 1920’s and 1930’s, the efforts of Hans Berger and Frederic and Erna Gibbs to develop and utilize EEG led to accurate pre-operative diagnoses of epilepsy along with their associated foci. Within that same time, the efforts of Wilder Penfield to develop and implement electrical cortical stimulation in awake patients during neurosurgery led to broad understandings of the organization and function of regions of the brain. Both EEG and cortical stimulation in combination quicky became useful beyond research in mapping the regions of the brain and led to rapid improvements in the accuracy of epilepsy surgery. Over preceding decades, these techniques continued to evolve with the latest research and technology. Additionally, their utilization has expanded from epilepsy surgery to resection for neoplasms of the central nervous system. In contemporary surgery, EEG and cortical stimulation still serve as the backbone of mapping techniques, but novel techniques are continually explored and improve patient outcomes. These advances include modern intraoperative neurophysiological monitoring, improved stimulation techniques, and additional utilization beyond the brain. This review highlights the conceptual underpinning of electrical neurophysiological mapping techniques as well as their implementation and future considerations. The review covers the pre-operative mapping of the brain using EEG, intraoperative mapping of the brain using cortical and subcortical mapping, and spinal cord mapping of the dorsal column and anterolateral tracts. The techniques and theory of each are summarized along with discussions on implementation and efficacy. Additional emphasis is placed on the need for standardization of their use to improve patient outcomes and recommendations for future research and development.

No description available.

No description available.

Spinal cord injury (SCI) causes life-long neurological impairment, with loss of sensory and motor function distal to the point of injury. There are approximately 300,000 patients living with SCI in the United States, and currently no effective treatment, reducing their quality of life. Amongst other things, proprioception, which has been determined essential for normal locomotion, can be lost with SCI. Epidural Electric Stimulation (EES), that is thought to excite large diameter afferent fibers (LDAF), has been found to improve recovery from spinal cord injury in conjunction with movement rehabilitation in animal models and humans. This represents an exciting new approach to help these patients. However, many open questions remain about how and why EES works. Chief among them are 1) which of the afferent fibers are necessary and sufficient to promote better recovery, and 2) what are the mechanisms of plasticity in the spinal cord that underly improvement. Here, we sought to address the first question by using viral and genetic tools to begin to target specific subsets of LDAF. First, we use a viral vector that preferably transduces only in the large diameter afferent fibers (LDAF) in the Dorsal Root Ganglia (DRG), and then specifically only the proprioceptors within the LDAF, by using a transgenic rat line that expresses Cre recombinase in Parvalbumin, a marker for proprioceptive neurons in the DRG. This approach consists of using the chemogenetic modulator of neuronal activity Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), which are activated by a putatively inert drug, clozapine-N-oxide (CNO), that crosses the blood brain barrier. While we were able to specifically target LDAF with excitatory DREADDs in L3-L5 DRGs in wild type rats, we were unsuccessful at specifically targeting proprioceptors by using the Pvalb-iCre rat line. Additionally, we studied the effect of exciting LDAF on rats with a 200KDyn SCI. CNO withdrawal on the week 7 stage of the recovery was associated with worse ladder performance than the previous and following weeks, as well as worse kinematic behavior of the same week on lower speeds in ankle movement. These results suggest that DREADDs activation is necessary for changes in movement at longer times post injury. It does not rule out that plasticity in neural circuitry has occurred but suggests that plasticity may rely on afferent activation. Finally, we sought to develop new methods to overcome skin motion artifact in rat kinematics by tattooing the knee area under the skin and recording infrared high-speed videos of moving rats which would correct joint calculations beyond just triangulation methods, as well as a novel MATLAB application that can accurately and reliably perform automated H-Reflex measurements, test the stimulating electrodes, and carry out typical instantaneous analyses, which in return allows for faster data collection with reduced human error, and subsequently result in higher research quality. / Bioengineering