Interaction of micron and nano-sized particles with cells of the dura mater.

Intervertebral total disc replacements (TDR) are used in the treatment of degenerative spinal disc disease. There are, however, concerns that they may be subject to long-term failure due to wear. The adverse effects of TDR wear have the potential to manifest in the dura mater and surrounding tissues. The aim of this study was to investigate the physiological structure of the dura mater, isolate the resident dural epithelial and stromal cells and analyse the capacity of these cells to internalise model polymer particles. The porcine dura mater was a collagen-rich structure encompassing regularly arranged fibroblastic cells within an outermost epithelial cell layer. The isolated dural epithelial cells had endothelial cell characteristics (positive for von Willebrand factor, CD31, E-cadherin and desmoplakin) and barrier functionality whereas the fibroblastic cells were positive for collagen I and III, tenascin and actin. The capacity of the dural cells to take up model particles was dependent on particle size. Nanometer sized particles readily penetrated both types of cells. However, dural fibroblasts engulfed micron-sized particles at a much higher rate than dural epithelial cells. The study suggested that dural epithelial cells may offer some barrier to the penetration of micron-sized particles but not nanometer sized particles

Regional mechanical and biochemical properties of the porcine cortical meninges

peer-reviewedThe meninges are pivotal in protecting the brain against traumatic brain injury (TBI), an ongoing issue in most mainstream sports. Improved understanding of TBI biomechanics and pathophysiology is desirable to improve preventative measures, such as protective helmets, and advance our TBI diagnostic/prognostic capabilities. This study mechanically characterised the porcine meninges by performing uniaxial tensile testing on the dura mater (DM) tissue adjacent to the frontal, parietal, temporal, and occipital lobes of the cerebellum and superior sagittal sinus region of the DM. Mechanical characterisation revealed a significantly higher elastic modulus for the superior sagittal sinus region when compared to other regions in the DM. The superior sagittal sinus and parietal regions of the DM also displayed local mechanical anisotropy. Further, fatigue was noted in the DM following ten preconditioning cycles, which could have important implications in the context of repetitive TBI. To further understand differences in regional mechanical properties, regional variations in protein content (collagen I, collagen III, fibronectin and elastin) were examined by immunoblot analysis. The superior sagittal sinus was found to have significantly higher collagen I, elastin, and fibronectin content. The frontal region was also identified to have significantly higher collagen I and fibronectin content while the temporal region had increased elastin and fibronectin content. Regional differences in the mechanical and biochemical properties along with regional tissue thickness differences within the DM reveal that the tissue is a non-homogeneous structure. In particular, the potentially influential role of the superior sagittal sinus in TBI biomechanics warrants further investigation

Functional and perceptive differences between conventional and advanced ankle foot orthoses in community ambulators post-limb trauma: the injuries managed with advanced bracing of the lower extremity (IM ABLE) study

IntroductionMany military service members and civilians suffer from lower extremity trauma. Despite recent advancements in lower limb bracing technology, it remains unclear whether these newer advanced braces offer improved comfort and functionality compared to conventional options. The IDEO (Intrepid Dynamic Exoskeletal Orthosis), a type of “advanced” orthosis was developed to assist in maintaining high functional performance in patients who have experienced high-energy lower extremity trauma and underwent limb salvage surgeries.MethodsA cross-sector multi-site initiative was completed to study the efficacy of advanced ankle foot orthoses (AFO) for lower limb trauma and injury compared to a conventional AFO. Following fitting, training, and accommodation, the subjects were assessed in each AFO system for mobility, self-reported function, safety and pain, and preference.ResultsThey preferred the advanced over the conventional AFO and the mobility and exertion perception improved with the advanced AFO with no difference in pain or overall health status scores.DiscussionThus, an advanced AFO is an option for trauma affecting the lower limb. Long-term studies are required to better understand the accommodation and learning process of using an advanced AFO

Intrathecal decompression versus epidural decompression in the treatment of severe spinal cord injury in rat model: a randomized, controlled preclinical research

Abstract Background In the setting of severe spinal cord injury (SCI), there is no markedly efficacious clinical therapeutic regimen to improve neurological function. After epidural decompression, as is shown in animal models, the swollen cord against non-elastic dura and elevation of intrathecal pressure may be the main causes of aggravated neurologic function. We performed an intrathecal decompression by longitudinal durotomy to evaluate the neuroprotective effect after severe SCI by comparing with epidural decompression. Methods Eighty-four adult male Sprague-Dawley rats were assigned to three groups: sham group (group S), epidural decompression (group C), and intrathecal decompression group (group D). A weight-drop model was performed at T9. The Basso-Beattie-Bresnahan (BBB) score was used to evaluate neurological function. Animals were sacrificed at corresponding time points, and we performed pathohistological examinations including HE staining and immunohistochemical staining (IHC) of glial fibrillary acidic protein (GFAP), neurocan, and ED1 at the epicenter of injured cords. Finally, the lesions were quantitatively analyzed by SPSS 22.0. Results The mortality rates were, respectively, 5.55 % (2/36) and 13.9 % (5/36) in groups C and D, and there was no significant difference between groups C and D (P = 0.214). Compared with epidural decompression, intrathecal decompression could obviously improve BBB scores after SCI. HE staining indicated that more white matter was spared, and fewer vacuoles and less axon degradation were observed. The expression peak of GFAP, neurocan, and ED1 occurred at an earlier time and was down-regulated in group D compared to group C. Conclusions Our findings based on rat SCI model suggest that intrathecal decompression by longitudinal durotomy can prompt recovery of neurological function, and this neuroprotective mechanism may be related to the down-regulation of GFAP, neurocan, and ED1.http://deepblue.lib.umich.edu/bitstream/2027.42/134548/1/13018_2016_Article_369.pd

In vivo tissue-level thresholds for spinal cord injury

Primary damage to the blood-spinal cord barrier (BSCB) is a nearly universal consequence of spinal cord injury that contributes significantly to the overall pathology. The in vivo tissue-level thresholds for mechanical disruption of the BSCB were identified by comparing the results of spinal cord contusions produced with weight drop injury to a finite element analysis (FEA) of the experimental model. The extent and severity of primary, physical disruption of the BSCB was quantified in adult rats five minutes after graded trauma induced with the Impactor weight drop model of spinal cord contusion. The volume of extravasation of three markers of distinct size -- fluorescently labeled hydrazide (~730Da), fluorescently labeled bovine serum albumin (~70kDa), and immunohistochemically labeled red blood cells (~5µm) was evaluated in both the gray and white matter. Extravasation volumes increased with increasing drop height and decreasing species size, and were greater in gray matter than in white matter. A three-dimensional finite element analysis of the weight drop model was performed and validated with the in vivo experimental peak displacement of the spinal cord at two loading conditions. The peak compression of the model was within ten percent of the experimental results. A parametric analysis revealed that the model was most sensitive to changes in the viscoelastic properties of the spinal cord. The finite element model provided temporal and spatial profiles of mechanical parameters that were used to identify tissue-level thresholds for BSCB injury using logistic regression analysis. Thirteen mechanical parameters, including measures of stress, strain, and strain rate were investigated as predictors of BSCB injury. Maximum principal strain (LEP) was considered the best predictor of injury in the gray matter, while von Mises strain (LEVM) was the best predictor of injury in the white matter, although the LEVM thresholds for white matter included relatively substantial error compared to the thresholds for gray matter. The results can be used to improve means and measures of preventing spinal cord injury in humans, define loading conditions for in vitro models of injury, and design new experimental models that produce specific patterns of injury.Ph.D.Includes bibliographical references (p. 218-229)

Implementation of relative phase analysis to evaluate continuous interlimb coordination and stability in individuals with lower limb loss: Design and protocol for a retrospective analysis

Introduction The number of people with lower limb loss continues to grow, though most research to date has been non-committal and lacks the appropriate clinical guidance required for proper prosthetic prescription. Previous literature using traditional spatiotemporal and biomechanical measures has not accurately identified differences in gait patterns when using different prosthetic devices. Therefore, a knowledge gap remains. To aid in determining the impact of different devices on gait in individuals with lower limb loss, a more sensitive quantitative measure should be used to supplement traditional biomechanical analyses. Continuous measures of coordination and stability, evaluated using relative phase analysis, has been shown to detect changes in gait patterns when traditional variables cannot. However, these measures have yet to be fully assessed in this population. This investigation will fill the knowledge gap by using relative phase analysis to provide a comprehensive description of kinematic behaviour by evaluating continuous interlimb coordination and stability for individuals with lower limb loss.Methods and analysis Biomechanical analysis of individuals with lower limb loss during walking activities will be evaluated using relative phase analysis to identify the continuous interlimb coordination and stability relationships between the upper and lower extremities of these individuals. Three-dimensional motion capture will enable kinematic properties of movement to be captured and analysed. Non-traditional measures of analysis will be used.Ethics and dissemination This study was approved by the Veterans Affairs New York Harbor Healthcare System Institutional Review Board (IRBNet #1573135, MIRB #1775). Findings will be disseminated through peer-reviewed publications, academic conference presentations, invited workshops, webinars and seminars

The Influence of Active, Passive, and Manual Therapy Interventions on Escalation of Health Care Events After Physical Therapist Care in Veterans With Low Back Pain

Objective The objective of this study was to examine the associations between active, passive, and manual therapy interventions with the escalation-of-care events following physical therapist care for veterans with low back pain (LBP). Methods A retrospective cohort study was conducted in 3618 veterans who received physical therapist care for LBP between January 1, 2015 and January 1, 2018. The VA Corporate Data Warehouse was utilized to identify LBP-related physical therapist visits and procedures, as well as opioid prescription and non-physical therapy clinic encounters. The association between physical therapist interventions with 1-year escalation-of-care events were assessed using adjusted odds ratios from logistic regression. Results Nearly all veterans (98%) received active interventions but only a minority (31%) received manual therapy. In the 1-year follow-up period, the odds of receiving an opioid prescription were 30% lower for those who received manual therapy in addition to active interventions, as compared with patients who received only active interventions. Moreover, the odds of receiving primary care, specialty care, and diagnostic testing were 30–130% higher for patients who received electrical stimulation or more than 1 passive intervention in addition to active treatments, as compared with patients who received only active interventions. Conclusion The use of manual therapy along with active interventions was associated with reduced prescription of opioids, while utilization of specific passive interventions such as electrical stimulation or multiple modalities in conjunction with active interventions resulted in increased escalation-of-care events. Impact Statement The use of active interventions, which is supported by most Clinical Practice Guidelines (CPGs), was the cornerstone of physical therapist care for veterans with LBP. However, the use of CPG-recommended manual therapy interventions was low but associated with reduced opioid prescriptions. The use of 2 or more different passive interventions along with active interventions was common (34%) and associated with less-than-optimal escalation-of-care outcomes