Histological and Ultrastructural Analysis of White Matter Damage after Naturally-occurring Spinal Cord Injury

Abstract- There are limited data on the lesion volume changes following spinal cord injury (SCI). In this study, a meta-analysis was performed to evaluate the volume size changes of the injured spinal cord over time among animal studies in traumatic SCI. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a comprehensive electronic search of English literature of PubMed and EMBASE databases from 1946 to 2015 concerning the time-dependent changes in the volume of the spinal cord following mechanical traumatic SCI. A hand-search was also performed for non-interventional, non-molecular, and non-review studies. Quality appraisal, data extraction, qualitative and quantitative analyses were performed afterward. Of 11,561 articles yielded from electronic search, 49 articles were assessed for eligibility after reviewing of titles, abstracts, and references. Ultimately, 11 articles were eligible for quantitative synthesis. The ratio of lesion volume to spinal cord total volume increased over time. Avascularity appeared in spinal cord 4 hours after injury. During the first week, the spinal subarachnoid space decreased. The hemorrhagic lesion size peaked in 1 week and decreased thereafter. Significant loss of gray and white matter occurred from day 3 with a slower progression of white matter damage. Changes of lesion extent over time is critical in pathophysiologic processes after SCI. Early avascularity, rapid loss of gray matter, slow progression of white matter damage, and late cavitation are the pathophysiologic key points of SCI, which could be helpful in choosing the proper intervention on a timely basis.

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Attenuation of White Matter Damage Following Deferoxamine Treatment in Rats After Spinal Cord Injury

World Neurosurgery ◽

10.1016/j.wneu.2019.08.246 ◽

2020 ◽

Vol 137 ◽

pp. e9-e17

Author(s):

Jiantao Shi ◽

Rongrui Tang ◽

Yi Zhou ◽

Jishu Xian ◽

Chenghai Zuo ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

White Matter ◽

White Matter Damage ◽

Cord Injury

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Ferrostatin-1 Alleviates White Matter Injury via Decreasing Ferroptosis Following Spinal Cord Injury

10.21203/rs.3.rs-405886/v1 ◽

2021 ◽

Author(s):

Hongfei Ge ◽

Xingsen Xue ◽

Jishu Xian ◽

Linbo Yuan ◽

Long Wang ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

White Matter ◽

Functional Recovery ◽

Underlying Mechanism ◽

Neurological Impairment ◽

White Matter Injury ◽

Oligodendrocyte Progenitor Cells ◽

White Matter Damage ◽

Cord Injury

Abstract Spinal cord injury (SCI), a devastating neurological impairment, ubiquitously imposes a long-term psychological stress and high socioeconomic burden for the suffers and their family. To date, recent researchers have paid arousing attention to white matter injury and uncovering the underlying mechanism post-SCI. Ferroptosis, to our knowledge, has been revealed to be associated with diverse diseases including stroke, cancer, and kidney degeneration. However, its role in white matter damage after SCI remains unclear. Ferrostatin-1, a potent inhibitor of ferroptosis, has been illustrated to curb ferroptosis in neurons, subsequently improve functional recovery after traumatic brain injury (TBI). But whether it inhibits white matter injury post-SCI is still unknown. Here, our results indicated that ferroptosis played an important role in the secondary white matter injury following SCI and ferrostatin-1 could reduce iron and reactive oxygen species (ROS) accumulation, downregulate the ferroptosis-related genes and its products of IREB2 and PTGS2 to further inhibit ferroptosis in oligodendrocyte progenitor cells (OPCs), finally reducing white matter injury and promoting functional recovery following SCI in rats, which enlarges the therapeutic scope for ferrostatin-1 and deciphers the potential mechanism of white matter damage after SCI.

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Docosahexaenoic Acid Prevents White Matter Damage after Spinal Cord Injury

Journal of Neurotrauma ◽

10.1089/neu.2010.1348 ◽

2010 ◽

Vol 27 (10) ◽

pp. 1769-1780 ◽

Cited By ~ 48

Author(s):

Rachael E. Ward ◽

Wenlong Huang ◽

Olympia E. Curran ◽

John V. Priestley ◽

Adina T. Michael-Titus

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

White Matter ◽

Docosahexaenoic Acid ◽

White Matter Damage ◽

Cord Injury

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White matter changes in corticospinal tract associated with improvement in arm and hand functions in incomplete cervical spinal cord injury: pilot case series

Spinal Cord Series and Cases ◽

10.1038/scsandc.2017.28 ◽

2017 ◽

Vol 3 (1) ◽

Cited By ~ 3

Author(s):

Nuray Yozbatiran ◽

Zafer Keser ◽

Khader Hasan ◽

Argyrios Stampas ◽

Radha Korupolu ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

White Matter ◽

Corticospinal Tract ◽

Cervical Spinal Cord ◽

Case Series ◽

Cervical Spinal Cord Injury ◽

White Matter Changes ◽

Hand Functions ◽

Cord Injury

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Contusion, dislocation, and distraction: primary hemorrhage and membrane permeability in distinct mechanisms of spinal cord injury

Journal of Neurosurgery Spine ◽

10.3171/spi.2007.6.3.255 ◽

2007 ◽

Vol 6 (3) ◽

pp. 255-266 ◽

Cited By ~ 85

Author(s):

Anthony M. Choo ◽

Jie Liu ◽

Clarrie K. Lam ◽

Marcel Dvorak ◽

Wolfram Tetzlaff ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

White Matter ◽

Animal Models ◽

Membrane Permeability ◽

High Speed ◽

Test System ◽

Fracture Dislocation ◽

Sprague Dawley ◽

Cord Injury

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.

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

Magnetic Resonance in Medicine ◽

10.1002/mrm.21316 ◽

2007 ◽

Vol 58 (2) ◽

pp. 253-260 ◽

Cited By ~ 129

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

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Numerical Investigation of Spinal Cord Injury After Flexion-Distraction Injuries At the Cervical Spine

Journal of Biomechanical Engineering ◽

10.1115/1.4052003 ◽

2021 ◽

Author(s):

Marie-Helene Beausejour ◽

Eric Wagnac ◽

Pierre-Jean Arnoux ◽

Jean-Marc Mac-Thiong ◽

Yvan Petit

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Cervical Spine ◽

White Matter ◽

Cervical Spinal Cord ◽

Element Model ◽

Von Mises Stress ◽

Study Objective ◽

Cord Injury ◽

Post Traumatic

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.

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