scholarly journals White matter regeneration induced by aligned fibrin nanofiber hydrogel contributes to motor functional recovery in canine T12 spinal cord injury

2021 ◽  
Author(s):  
Zheng Cao ◽  
Weitao Man ◽  
Yuhui Xiong ◽  
Yi Guo ◽  
Shuhui Yang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
White Matter ◽  
Nerve Regeneration ◽  
Spinal Cord Injuries ◽  
Diffusion Tensor ◽  
Nerve Fibers ◽  
Functional Restoration ◽  
Large Animal ◽  
Cord Injury

Abstract A hierarchically aligned fibrin hydrogel (AFG) that possesses soft stiffness and aligned nanofiber structure has been successfully proven to facilitate neuroregeneration in vitro and in vivo. However, its potential in promoting nerve regeneration in large animal models that is critical for clinical translation has not been sufficiently specified. Here, the effects of AFG on directing neuroregeneration in canine hemisected T12 spinal cord injuries were explored. Histologically obvious white matter regeneration consisting of a large area of consecutive, compact, and aligned nerve fibers is induced by AFG, leading to a significant motor functional restoration. The canines with AFG implantation start to stand well with their defective legs from 3 to 4 weeks postoperatively and even effortlessly climb the steps from 7 to 8 weeks. Moreover, high-resolution multi-shot diffusion tensor imaging illustrates the spatiotemporal dynamics of nerve regeneration rapidly crossing the lesion within 4 weeks in the AFG group. Our findings indicate that AFG could be a potential therapeutic vehicle for spinal cord injury by inducing rapid white matter regeneration and restoring locomotion, pointing out its promising prospect in clinic practice.

scholarly journals Collagen/heparin sulfate scaffold combined with mesenchymal stem cells treatment for canines with spinal cord injury: A pilot feasibility study

2021 ◽  
Vol 29 (2) ◽  
pp. 230949902110122
Author(s):  
Wu-Sheng Deng ◽  
Kun Yang ◽  
Bing Liang ◽  
Ying-Fu Liu ◽  
Xu-Yi Chen ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Nerve Regeneration ◽  
Diffusion Tensor ◽  
Nerve Fibers ◽  
Glial Scar ◽  
Heparin Sulfate ◽  
Cord Injury

Background: Due to endogenous neuronal deficiency and glial scar formation, spinal cord injury (SCI) often leads to irreversible neurological loss. Accumulating evidence has shown that a suitable scaffold has important value for promoting nerve regeneration after SCI. Collagen/heparin sulfate scaffold (CHSS) has shown effect for guiding axonal regeneration and decreasing glial scar deposition after SCI. The current research aimed to evaluate the utility of the CHSSs adsorbed with mesenchymal stem cells (MSCs) on nerve regeneration, and functional recovery after acute complete SCI. Methods: CHSSs were prepared, and evaluated for biocompatibility. The CHSSs adsorbed with MSCs were transplanted into these canines with complete SCI. Results: We observed that MSCs had good biocompatibility with CHSSs. In complete transverse SCI models, the implantation of CHSS co-cultured with MSCs exhibited significant improvement in locomotion, motor evoked potential, magnetic resonance imaging, diffusion tensor imaging, and urodynamic parameters. Meanwhile, nerve fibers were markedly improved in the CHSS adsorbed with MSCs group. Moreover, we observed that the implantation of CHSS combined with MSCs modulated inflammatory cytokine levels. Conclusions: The results preliminarily demonstrated that the transplantation of MSCs on a CHSS could improve the recovery of motor function after SCI. Thus, implanting the MSCs-laden CHSS is a promising combinatorial therapy for treatment in acute SCI.

scholarly journals Noninvasive diffusion tensor imaging of evolving white matter pathology in a mouse model of acute spinal cord injury

2007 ◽  
Vol 58 (2) ◽  
pp. 253-260 ◽  
Author(s):  
Joong Hee Kim ◽  
David N. Loy ◽  
Hsiao-Fang Liang ◽  
Kathryn Trinkaus ◽  
Robert E. Schmidt ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Diffusion Tensor Imaging ◽  
White Matter ◽  
Mouse Model ◽  
Diffusion Tensor ◽  
Acute Spinal Cord Injury ◽  
Cord Injury ◽  
White Matter Pathology

scholarly journals Epidural Stimulation Combined with Triple Gene Therapy for Spinal Cord Injury Treatment

2020 ◽  
Vol 21 (23) ◽  
pp. 8896
Author(s):  
Rustem Islamov ◽  
Farid Bashirov ◽  
Filip Fadeev ◽  
Roman Shevchenko ◽  
Andrei Izmailov ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Gene Therapy ◽  
Spinal Cord Injury ◽  
Combined Treatment ◽  
Small Sample ◽  
Functional Restoration ◽  
Synaptic Proteins ◽  
Large Animal ◽  
Cord Injury ◽  
Spinal Contusion

The translation of new therapies for spinal cord injury to clinical trials can be facilitated with large animal models close in morpho-physiological scale to humans. Here, we report functional restoration and morphological reorganization after spinal contusion in pigs, following a combined treatment of locomotor training facilitated with epidural electrical stimulation (EES) and cell-mediated triple gene therapy with umbilical cord blood mononuclear cells overexpressing recombinant vascular endothelial growth factor, glial-derived neurotrophic factor, and neural cell adhesion molecule. Preliminary results obtained on a small sample of pigs 2 months after spinal contusion revealed the difference in post-traumatic spinal cord outcomes in control and treated animals. In treated pigs, motor performance was enabled by EES and the corresponding morpho-functional changes in hind limb skeletal muscles were accompanied by the reorganization of the glial cell, the reaction of stress cell, and synaptic proteins. Our data demonstrate effects of combined EES-facilitated motor training and cell-mediated triple gene therapy after spinal contusion in large animals, informing a background for further animal studies and clinical translation.

scholarly journals (A313) Role of Physiatrists in Post Disaster Scenarios - Lessons Learned from Pakistan, China and Haiti Earthquakes

2011 ◽  
Vol 26 (S1) ◽  
pp. s105-s105
Author(s):  
F.A. Rathore ◽  
C. O'connell ◽  
J. Li
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Spinal Cord Injuries ◽  
Community Integration ◽  
Functional Restoration ◽  
Lessons Learned ◽  
Spinal Trauma ◽  
Trauma Patients ◽  
Cord Injury ◽  
Post Disaster

IntroductionPhysical Medicine and Rehabilitation is a goal oriented and patient centered specialty which focuses on functional restoration and quality of life of persons with disability. The patterns of injuries among survivors of recent disasters have, range from mild (single limb fracture) to catastrophic (spinal cord injury, amputation, traumatic brain injury). Historically physiatrists have not participated the acute disaster management phase or in the emergent post disaster rehabilitation planning. This task is usually relegated to the trauma, orthopedic and general surgeons.MethodologyAuthors had firsthand experience in the acute and emergent care and rehabilitation of trauma patients after Pakistan, China and Haiti earthquakes. An electronic literature search (English, 1965–2010, Key words: trauma, rehabilitation, disability, spinal cord injury, amputation, disaster, nerve injury) was carried out. Experience sharing through committees, online forum, and communications were conducted with physiatry colleagues internationally.ResultsIn these three recent earthquakes, Physiatrists provided direct patient care, including guidance in the evacuation of survivors with pre-existing disabilities, transport of persons with spinal trauma, treatment of wounds, fractures, pain, spinal trauma patients and persons with amputations. Physiatrists devised appropriate plans for conservative management of fractures. Education of local staff and coordination of rehabilitation was initiated. Monitoring, prevention and treatment of secondary complications including prolonged immobility, pressure ulcers, chronic pain, urinary, bowel and respiratory dysfunction was performed. Physiatrists helped in patient counseling and family education.ConclusionPhysiatrists by virtue of their training and skills are in a better position to manage the disabilities, including direction of rehabilitation and community integration, prevention of complications, and education and training of health workers and teams. Timely rehabilitation interventions for Spinal cord injuries and lower limb amputations following the Pakistan, China and Haiti earthquakes resulted in reduction in morbidity and mortality among those with catastrophic injuries.

Identification of Severities of Spinal Cord Injury during Acute Phase in Rats by Diffusion Tensor Imaging

2020 ◽  
Author(s):  
Beike Chen ◽  
Qiang Tan ◽  
Weikang Zhao ◽  
Qiming Yang ◽  
Hongyan Zhang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Diffusion Tensor Imaging ◽  
White Matter ◽  
Diffusion Tensor ◽  
Motor Evoked Potentials ◽  
Ex Vivo ◽  
Female Rats ◽  
Aneurysm Clip ◽  
Cord Injury

Abstract Background: Diffusion tensor imaging (DTI) was an effective method to identify subtle changes to normal‐appearing white matter (WM). Here we analyzed the DTI data with other examinations, including motor evoked potentials (MEPs), histopathological images, and behavioral results, to reflect the lesion development in different degrees of spinal cord injury (SCI) in acute and subacute stage. Method: Except for 2 Sprague -Dawley rats died from anesthesia accident, the rest 42 female rats were randomized into 3 groups: control (n=6), moderate group (n=18), and severe group (n=18). Moderate (a 50-g aneurysm clip with 0.4-mm thickness spacer) or severe (a 50-g aneurysm clip with no spacer) contusion SCI at T8 vertebrae were induced. Then the electrophysiological assessments via MEPs, behavioral deterioration via the Basso, Beattie, and Bresnaha (BBB) scores, DTI data, and histopathology examination were analyzed. Results: In this study, we found that the damage of WM myelin, MEPs amplitude, BBB scores and the decreases in values of fractional anisotropy (FA) and axial diffusivity (AD) were more obvious in the severe injury group than that of the moderate group. Additionally, the FA and AD values could identify the extent of SCI in subacute and early acute SCI respectively, reflected in the robust correlations with MEPs and BBB scores. While the values of radial diffusivity (RD) showed no significant changes. Conclusions: Our data confirmed that DTI was a valuable in ex vivo imaging tool to identify damaged white matter tracts after graded SCI in rat, which may provide useful information for the early identification of the severity of SCI.

scholarly journals Longitudinal changes in DTI parameters of specific spinal white matter tracts correlate with behavior following spinal cord injury in monkeys

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Arabinda Mishra ◽  
Feng Wang ◽  
Li Min Chen ◽  
John C. Gore
Keyword(s):  
Spinal Cord ◽  
White Matter ◽  
Spinal Cord Injuries ◽  
Diffusion Tensor ◽  
Cervical Spinal Cord ◽  
Human Subjects ◽  
Realistic Model ◽  
White Matter Tracts ◽  
Injured Side ◽  
Cord Injury

Abstract This study aims to evaluate how parameters derived from diffusion tensor imaging reflect axonal disruption and demyelination in specific white matter tracts within the spinal cord of squirrel monkeys following traumatic injuries, and their relationships to function and behavior. After a unilateral section of the dorsal white matter tract of the cervical spinal cord, we found that both lesioned dorsal and intact lateral tracts on the lesion side exhibited prominent disruptions in fiber orientation, integrity and myelination. The degrees of pathological changes were significantly more severe in segments below the lesion than above. The lateral tract on the opposite (non-injured) side was minimally affected by the injury. Over time, RD, FA, and AD values of the dorsal and lateral tracts on the injured side closely tracked measurements of the behavioral recovery. This unilateral section of the dorsal spinal tract provides a realistic model in which axonal disruption and demyelination occur together in the cord. Our data show that specific tract and segmental FA and RD values are sensitive to the effects of injury and reflect specific behavioral changes, indicating their potential as relevant indicators of recovery or for assessing treatment outcomes. These observations have translational value for guiding future studies of human subjects with spinal cord injuries.

scholarly journals Investigation of Cerebral White Matter Changes After Spinal Cord Injury With a Measure of Fiber Density

2021 ◽  
Vol 12 ◽  
Author(s):  
Vincent Huynh ◽  
Philipp Staempfli ◽  
Robin Luetolf ◽  
Roger Luechinger ◽  
Armin Curt ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
White Matter ◽  
Motor Function ◽  
Roc Analysis ◽  
Diffusion Tensor ◽  
Tensor Model ◽  
Fiber Density ◽  
Microstructural Changes ◽  
Cord Injury

Remote neurodegenerative changes in supraspinal white matter (WM) can manifest after central lesions such as spinal cord injury (SCI). The majority of diffusion tensor imaging (DTI) studies use traditional metrics such as fractional anisotropy (FA) and mean diffusivity (MD) to investigate microstructural changes in cerebral WM after SCI. However, interpretation of FA readouts is often challenged by inherent limitations of the tensor model. Recent developments in novel diffusion markers, such as fiber density (FD), allows more accurate depictions of WM pathways and has shown more reliable quantification of WM alterations compared to FA in recent studies of neurological diseases. This study investigated if FD provides useful characterization of supraspinal WM integrity after SCI in addition to the traditional DTI readouts. FA, MD, and FD maps were derived from diffusion datasets of 20 patients with chronic SCI and compared with 19 healthy controls (HC). Group differences were investigated across whole brain WM using tract-based spatial statistics and averaged diffusion values of the corticospinal tract (CST) and thalamic radiation (TR) were extracted for comparisons between HC and SCI subgroups. We also related diffusion readouts of the CST and TR with clinical scores of sensorimotor function. To investigate which diffusion markers of the CST and TR delineate HC and patients with SCI a receiver operating characteristic (ROC) analysis was performed. Overall, patients with an SCI showed decreased FA of the TR and CST. ROC analysis differentiated HC and SCI based on diffusion markers of large WM tracts including FD of the TR. Furthermore, patients' motor function was positively correlated with greater microstructural integrity of the CST. While FD showed the strongest correlation, motor function was also associated with FA and MD of the CST. In summary, microstructural changes of supraspinal WM in patients with SCI can be detected using FD as a complementary marker to traditional DTI readouts and correlates with their clinical characteristics. Future DTI studies may benefit from utilizing this novel marker to investigate complex large WM tracts in patient cohorts with varying presentations of SCI or neurodegenerative diseases.

scholarly journals Extent of cord pathology in the lumbosacral enlargement in non-traumatic versus traumatic spinal cord injury

2021 ◽  
Author(s):  
Gergely David ◽  
Kevin Vallotton ◽  
Markus Hupp ◽  
Armin Curt ◽  
Patrick Freund ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
White Matter ◽  
Fractional Anisotropy ◽  
Diffusion Tensor ◽  
Similar Degree ◽  
Traumatic Spinal Cord Injury ◽  
Healthy Controls ◽  
Lateral Column ◽  
Cord Injury

Objectives: This study compares remote neurodegenerative changes caudal to a cervical injury in degenerative cervical myelopathy (DCM) (i.e. non-traumatic) and incomplete traumatic spinal cord injury (tSCI) patients, using MRI-based tissue area measurements and diffusion tensor imaging (DTI). Methods: Eighteen mild to moderate DCM patients with sensory impairments (mean mJOA score: 16.2), 14 incomplete tetraplegic tSCI patients (AIS C&D), and 20 healthy controls were recruited. All participants received DTI and T2*-weighted scans in the lumbosacral enlargement (caudal to injury) and at C2/C3 (rostral to injury). MRI readouts included DTI metrics in the white matter (WM) columns and cross-sectional WM and gray matter area. One-way ANOVA with Tukey post-hoc comparison (p<0.05) was used to assess group differences. Results: In the lumbosacral enlargement, compared to DCM, tSCI patients exhibited decreased fractional anisotropy in the lateral (tSCI vs. DCM, -11.9%, p=0.007) and ventral WM column (-8.0%, p=0.021), and showed trend toward lower values in the dorsal column (-8.9%, p=0.068). At C2/C3, no differences in DTI metrics were observed between DCM and tSCI, but compared to controls, fractional anisotropy was lower in both groups in the dorsal (DCM vs. controls, -7.9%, p=0.024; tSCI vs. controls, -10.0%, p=0.007) and in the lateral column (DCM: -6.2%, p=0.039; tSCI: -13.3%, p<0.001). WM areas were not different between patient groups, but were significantly lower compared to healthy controls both in the lumbosacral enlargement (DCM: -16.9%, p<0.001; tSCI, -10.5%, p=0.043) and at C2/C3 (DCM: -16.0%, p<0.001; tSCI: -18.1%, p<0.001). Conclusion: In conclusion, mild to moderate DCM and incomplete tSCI lead to similar degree of degeneration of the dorsal and lateral columns at C2/C3, but tSCI results in more widespread white matter damage in the lumbosacral enlargement. These remote changes are likely to contribute to the impairment and recovery of the patients. Diffusion MRI is a sensitive tool to assess remote pathological changes in DCM and tSCI patients.

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