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 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 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 Rapamycin Preserves Neural Tissue, Promotes Schwann Cell Myelination and Reduces Glial Scar Formation After Hemi-Contusion Spinal Cord Injury in Mice

2021 ◽  
Vol 13 ◽  
Author(s):  
Junhao Liu ◽  
Ruoyao Li ◽  
Zucheng Huang ◽  
Junyu Lin ◽  
Wei Ji ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
White Matter ◽  
Schwann Cell ◽  
Motor Function ◽  
Neural Tissue ◽  
Glial Scar ◽  
Vehicle Group ◽  
Spinal Cord Tissue ◽  
Cord Injury

Protecting white matter is one of the key treatment strategies for spinal cord injury (SCI), including alleviation of myelin loss and promotion of remyelination. Rapamycin has been shown neuroprotective effects against SCI and cardiotoxic effects while enhancing autophagy. However, specific neuroprotection of rapamycin for the white matter after cervical SCI has not been reported. Therefore, we aim to evaluate the role of rapamycin in neuroprotection after hemi-contusion SCI in mice. Forty-six 8-week-old mice were randomly assigned into the rapamycin group (n = 16), vehicle group (n = 16), and sham group (n = 10). All mice of the rapamycin and vehicle groups received a unilateral contusion with 1.2-mm displacement at C5 followed by daily intraperitoneal injection of rapamycin or dimethyl sulfoxide solution (1.5 mg⋅kg–1⋅day–1). The behavioral assessment was conducted before the injury, 3 days and every 2 weeks post-injury (WPI). The autophagy-related proteins, the area of spared white matter, the number of oligodendrocytes (OLs) and axons were evaluated at 12 WPI, as well as the glial scar and the myelin sheaths formed by Schwann cells at the epicenter. The 1.2 mm contusion led to a consistent moderate–severe SCI in terms of motor function and tissue damage. Rapamycin administration promoted autophagy in spinal cord tissue after injury and reduced the glial scar at the epicenter. Additionally, rapamycin increased the number of OLs and improved motor function significantly than in the vehicle group. Furthermore, the rapamycin injection resulted in an increase of Schwann cell-mediated remyelination and weight loss. Our results suggest that rapamycin can enhance autophagy, promote Schwann cell myelination and motor function recovery by preserved neural tissue, and reduce glial scar after hemi-contusive cervical SCI, indicating a potential strategy for SCI treatment.

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 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.

scholarly journals Testing Pathological Variation of White Matter Tract in Adult Rats after Severe Spinal Cord Injury with MRI

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Wei Song ◽  
Guiyun Song ◽  
Can Zhao ◽  
Xiaoguang Li ◽  
Xiaojiao Pei ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
White Matter ◽  
Motor Function ◽  
Critical Role ◽  
White Matter Tract ◽  
Noninvasive Technique ◽  
Function Recovery ◽  
Cord Injury

The purpose of this study was to assess the pathological variation in white matter tracts in the adult severe thoracic contusion spinal cord injury (SCI) rat models combined with in vivo magnetic resonance imaging (MRI), as well as the effect of spared white matter (WM) quantity on hindlimb motor function recovery. 7.0T MRI was conducted for all experimental animals before SCI and 1, 3, 7, and 14 days after SCI. The variation in the white matter tract in different regions of the spinal cord after SCI was examined by luxol fast blue (LFB) staining, NF200 immunochemistry, and diffusion tensor imaging (DTI) parameters, including fraction anisotropy, mean diffusivity, axial diffusion, and radial diffusivity. Meanwhile, Basso-Beattie-Bresnahan (BBB) open-field scoring was performed to evaluate the behavior of the paraplegic hind limbs. The quantitative analysis showed that spared white matter measures assessed by LFB and MRI had a close correlation (R2 = 0.8508). The percentage of spared white matter area was closely correlated with BBB score (R2 = 0.8460). After SCI, spared white matter in the spinal cord, especially the ventral column WM, played a critical role in motor function restoration. The results suggest that the first three days provides a key time window for SCI protection and treatment; spared white matter, especially in the ventral column, plays a key role in motor function recovery in rats. Additionally, DTI may be an important noninvasive technique to diagnose acute SCI degree as well as a tool to evaluate functional prognosis. During the transition from nerve protection toward clinical treatment after SCI, in vivo DTI may serve as an emerging noninvasive technique to diagnose acute SCI degree and predict the degree of spontaneous functional recovery after SCI.

scholarly journals Plasma Erythropoietin, IL-17A, and IFNγ as Potential Biomarkers of Motor Function Recovery in a Canine Model of Spinal Cord Injury

2020 ◽  
Vol 70 (11) ◽  
pp. 1821-1828 ◽  
Author(s):  
Lijian Zhang ◽  
Xiaoqing Zhuang ◽  
Yao Chen ◽  
Zhanfeng Niu ◽  
Hechun Xia
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Function ◽  
Roc Analysis ◽  
Characteristic Curve ◽  
Enzyme Linked Immunosorbent Assay ◽  
Plasma Cytokine ◽  
Function Recovery ◽  
Cord Injury ◽  
Neurochemical Changes

Abstract Traumatic spinal cord injury (SCI) is a devastating neurological disease for which an accurate, cost-effective prediction of motor function recovery is in pressing need. A plethora of neurochemical changes involved in the pathophysiological process of SCI may serve as a new source of biomarkers for patient outcomes. Five dogs were included in this study. We characterized the plasma cytokine profiles in acute phase (0, 1, and 3 days after SCI) and subacute phase (7, 14, and 21 days after SCI) with microarray analysis. The motor function recovery following SCI was monitored by Olby scores. The expression level of differentially expressed proteins (DEPs) was measured with enzyme-linked immunosorbent assay (ELISA). Then, correlations with the Olby scores and receiver operating characteristic curve (ROC) analysis were performed. We identified 12 DEPs including 10 pro-inflammatory and 2 anti-inflammatory cytokines during the 21-day study period. Among those, the expression levels of erythropoietin (EPO), IL-17A, and IFNγ significantly correlated with the Olby scores with R2 values of 0.870, 0.740, and 0.616, respectively. The results of the ROC analysis suggested that plasma EPO, IL-17A, and IFNγ exhibited a significant predictive power with an area under the curve (AUC) of 0.656, 0.848, and 0.800 for EPO, IL-17A, and IFNγ, respectively. Our results provide a longitudinal description of the changes in plasma cytokine expression in the acute and subacute stages of canine SCI. These data reveal novel panels of inflammation-related cytokines which have the potential to be evaluated as biomarkers for predicting motor function prognosis after SCI.

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