scholarly journals Spinal cord injury induces widespread chronic changes in cerebral white matter

Author(s):  
Tero Ilvesmäki ◽  
Eerika Koskinen ◽  
Antti Brander ◽  
Teemu Luoto ◽  
Juha Öhman ◽  
...  
2007 ◽  
Vol 6 (3) ◽  
pp. 255-266 ◽  
Author(s):  
Anthony M. Choo ◽  
Jie Liu ◽  
Clarrie K. Lam ◽  
Marcel Dvorak ◽  
Wolfram Tetzlaff ◽  
...  

Object In experimental models of spinal cord injury (SCI) researchers have typically focused on contusion and transection injuries. Clinically, however, other injury mechanisms such as fracture–dislocation and distraction also frequently occur. The objective of the present study was to compare the primary damage in three clinically relevant animal models of SCI. Methods Contusion, fracture–dislocation, and flexion–distraction animal models of SCI were developed. To visualize traumatic increases in cellular membrane permeability, fluorescein–dextran was infused into the cerebrospi-nal fluid prior to injury. High-speed injuries (approaching 100 cm/second) were produced in the cervical spine of deeply anesthetized Sprague–Dawley rats (28 SCI and eight sham treated) with a novel multimechanism SCI test system. The animals were killed immediately thereafter so that the authors could characterize the primary injury in the gray and white matter. Sections stained with H & E showed that contusion and dislocation injuries resulted in similar central damage to the gray matter vasculature whereas no overt hemorrhage was detected following distraction. Contusion resulted in membrane disruption of neuronal somata and axons localized within 1 mm of the lesion epicenter. In contrast, membrane compromise in the dislocation and distraction models was observed to extend rostrally up to 5 mm, particularly in the ventral and lateral white matter tracts. Conclusions Given the pivotal nature of hemorrhagic necrosis and plasma membrane compromise in the initiation of downstream SCI pathomechanisms, the aforementioned differences suggest the presence of mechanism-specific injury regions, which may alter future clinical treatment paradigms.


2007 ◽  
Vol 58 (2) ◽  
pp. 253-260 ◽  
Author(s):  
Joong Hee Kim ◽  
David N. Loy ◽  
Hsiao-Fang Liang ◽  
Kathryn Trinkaus ◽  
Robert E. Schmidt ◽  
...  

Author(s):  
Marie-Helene Beausejour ◽  
Eric Wagnac ◽  
Pierre-Jean Arnoux ◽  
Jean-Marc Mac-Thiong ◽  
Yvan Petit

Abstract Flexion-distraction injuries frequently cause traumatic cervical spinal cord injury (SCI). Post-traumatic instability can cause aggravation of the secondary SCI during patient's care. However, there is little information on how the pattern of disco-ligamentous injury affects the SCI severity and mechanism. This study objective was to analyze how different flexion-distraction disco-ligamentous injuries affect the SCI mechanisms during post-traumatic flexion and extension. A cervical spine finite element model including the spinal cord was used and different combinations of partial or complete intervertebral disc (IVD) rupture and disruption of various posterior ligaments were modeled at C4-C5, C5-C6 or C6-C7. In flexion, complete IVD rupture combined with posterior ligamentous complex rupture was the most severe injury leading to the most extreme von Mises stress (47 to 66 kPa), principal strains p1 (0.32 to 0.41 in white matter) and p3 (-0.78 to -0.96 in white matter) in the spinal cord and to the most important spinal cord compression (35 to 48 %). The main post-trauma SCI mechanism was identified as compression of the anterior white matter at the injured level combined with distraction of the posterior spinal cord during flexion. There was also a concentration of the maximum stresses in the gray matter after injury. Finally, in extension, the injuries tested had little impact on the spinal cord. The capsular ligament was the most important structure in protecting the spinal cord. Its status should be carefully examined during patient's management.


2021 ◽  
Author(s):  
Zheng Cao ◽  
Weitao Man ◽  
Yuhui Xiong ◽  
Yi Guo ◽  
Shuhui Yang ◽  
...  

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.


2001 ◽  
Vol 94 (2) ◽  
pp. 257-264 ◽  
Author(s):  
Mercedes Zurita ◽  
Jesús Vaquero ◽  
Isabel Zurita

Object. A glycoprotein, CD95 (Fas/APO1) is widely considered to be implicated in the development of apoptosis in a number of tissues. Based on the hypothesis that apoptosis is related to cell death after spinal cord injury (SCI), the authors studied the presence and distribution of CD95 (Fas/APO1)-positive cells in injured spinal cord tissue for the purpose of determining the significance of this protein during the early phases of SCI. Methods. The presence and distribution of cells showing positive immunostaining for CD95 (Fas/APO1) were studied 1, 4, 8, 24, 48, and 72 hours and 1, 2, and 4 weeks after induction of experimental SCI in rats. Studies were conducted using a monoclonal antibody to the CD95 (Fas/APO1) protein. Positivity for CD95 (Fas/APO1) was observed in apoptotic cells, mainly in the gray matter, 1 hour after trauma, and the number of immunostained cells increased for the first 8 hours, at which time the protein was expressed in both gray and white matter. From 24 to 72 hours postinjury, the number of immunostained cells decreased in the gray matter, but increased in the white matter. From then on, there were fewer CD95 (Fas/APO1)-positive cells, but some cells in the white matter still exhibited positive immunostaining 1 and 2 weeks after injury. At 4 weeks, there remained no CD95 (Fas/APO1)-positive cells in injured spinal cord. Conclusions. These findings indicate that CD95 (Fas/APO1) is expressed after SCI, suggesting a role for this protein in the development of apoptosis after trauma and the possibility of a new therapeutic approach to SCI based on blocking the CD95 (Fas/APO1) system.


Nano LIFE ◽  
2015 ◽  
Vol 05 (04) ◽  
pp. 1550004 ◽  
Author(s):  
Suneel Kumar ◽  
Joanne Babiarz ◽  
Sayantani Basak ◽  
Jae Hwan Kim ◽  
Jeffrey Barminko ◽  
...  

Microencapsulation of mesenchymal stem cells (MSC) in alginate facilitates cell delivery, localization and survival, and modulates inflammation in vivo. However, we found that delivery of the widely used ∼ 0.5mm diameter encapsulated MSC (eMSC) by intrathecal injection into spinal cord injury (SCI) rats was highly variable. Injections of smaller (∼ 0.2 mm) diameter eMSC into the lumbar spine were much more reproducible and they increased the anti-inflammatory macrophage response around the SCI site. We now report that injection of small eMSC [Formula: see text][Formula: see text]cm caudal from the rat SCI improved locomotion and myelin preservation 8 weeks after rat SCI versus control injections. Because preparation of sufficient quantities of small eMSC for larger studies was not feasible and injection of the large eMSC is problematic, we have developed a procedure to prepare medium-sized eMSC ([Formula: see text][Formula: see text]mm diameter) that can be delivered more reproducibly into the lumbar rat spine. The number of MSC incorporated/capsule in the medium sized capsules was [Formula: see text]5-fold greater than that in small capsules and the total yield of eMSC was ∼ 20-fold higher than that for the small capsules. Assays with all three sizes of eMSC capsules showed that they inhibited TNF-[Formula: see text] secretion from activated macrophages in co-cultures, suggesting no major difference in their anti-inflammatory activity in vitro. The in vivo activity of the medium-sized eMSC was tested after injecting them into the lumbar spine 1 day after SCI. Histological analyses 1 week later showed that eMSC reduced levels of activated macrophages measured by IB4 staining and increased white matter sparing in similar regions adjacent to the SCI site. The combined results indicate that ∼ 0.35 mm diameter eMSC reduced macrophage inflammation in regions where white matter was preserved during critical early phases after SCI. These techniques enable preparation of eMSC in sufficient quantities to perform pre-clinical SCI studies with much larger numbers of subjects that will provide functional analyses of several critical parameters in rodent models for CNS inflammatory injury.


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