Vascular mechanisms in the pathophysiology of human spinal cord injury

1997 ◽  
Vol 86 (3) ◽  
pp. 483-492 ◽  
Author(s):  
Charles H. Tator ◽  
Izumi Koyanagi
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
White Matter ◽  
Gray Matter ◽  
White Matter Lesions ◽  
Arterial System ◽  
Secondary Injury ◽  
Human Spinal Cord ◽  
Injury Mechanisms ◽  
Cord Injury

✓ Vascular injury plays an important role in the primary and secondary injury mechanisms that cause damage to the acutely traumatized spinal cord. To understand the pathophysiology of human spinal cord injury, the authors investigated the vascular system in three uninjured human spinal cords using silicone rubber microangiography and analyzed the histological findings related to vascular injury in nine acutely traumatized human spinal cords obtained at autopsy. The interval from spinal cord injury to death ranged from 20 minutes to 9 months. The microangiograms of the uninjured human cervical cords demonstrated new information about the sulcal arterial system and the pial arteries. The centrifugal sulcal arterial system was found to supply all of the anterior gray matter, the anterior half of the posterior gray matter, approximately the inner half of the anterior and lateral white columns, and the anterior half of the posterior white columns. Traumatized spinal cord specimens in the acute stage (3–5 days postinjury) showed severe hemorrhages predominantly in the gray matter, but also in the white matter. The white matter surrounding the hemorrhagic gray matter showed a variety of lesions, including decreased staining, disrupted myelin, and axonal and periaxonal swelling. The white matter lesions extended far from the injury site, especially in the posterior columns. There was no evidence of complete occlusion of any of the larger arteries, including the anterior and posterior spinal arteries and the sulcal arteries. However, occluded intramedullary veins were identified in the degenerated posterior white columns. In the chronic stage (3–9 months postinjury), the injured segments showed major tissue loss with large cavitations, whereas both rostral and caudal remote sites showed well-demarcated necrotic areas indicative of infarction mainly in the posterior white columns. Obstruction of small intramedullary arteries and veins by the initial mechanical stress or secondary injury mechanisms most likely produced these extensive white matter lesions. Our studies implicate damage to the anterior sulcal arteries in causing the hemorrhagic necrosis and subsequent central myelomalacia at the injury site in acute spinal cord injury in humans.

scholarly journals Vascular mechanisms in the pathophysiology of human spinal cord injury

1997 ◽  
Vol 2 (1) ◽  
pp. E2
Author(s):  
Charles H. Tator ◽  
Izumi Koyanagi
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
White Matter ◽  
Gray Matter ◽  
White Matter Lesions ◽  
Arterial System ◽  
Secondary Injury ◽  
Human Spinal Cord ◽  
Injury Mechanisms ◽  
Cord Injury

Vascular injury plays an important role in the primary and secondary injury mechanisms that cause damage to the acutely traumatized spinal cord. To understand the pathophysiology of human spinal cord injury, the authors investigated the vascular system in three uninjured human spinal cords using silicone rubber microangiography and analyzed the histological findings related to vascular injury in nine acutely traumatized human spinal cords obtained at autopsy. The interval from spinal cord injury to death ranged from 20 minutes to 9 months. The microangiograms of the uninjured human cervical cords demonstrated new information about the sulcal arterial system and the pial arteries. The centrifugal sulcal arterial system was found to supply all of the anterior gray matter, the anterior half of the posterior gray matter, approximately the inner half of the anterior and lateral white columns, and the anterior half of the posterior white columns. Traumatized spinal cord specimens in the acute stage (3-5 days postinjury) showed severe hemorrhages predominantly in the gray matter, but also in the white matter. The white matter surrounding the hemorrhagic gray matter showed a variety of lesions, including decreased staining, disrupted myelin, and axonal and periaxonal swelling. The white matter lesions extended far from the injury site, especially in the posterior columns. There was no evidence of complete occlusion of any of the larger arteries, including the anterior and posterior spinal arteries and the sulcal arteries. However, occluded intramedullary veins were identified in the degenerated posterior white columns. In the chronic stage (3-9 months postinjury), the injured segments showed major tissue loss with large cavitations, whereas both rostral and caudal remote sites showed well-demarcated necrotic areas indicative of infarction mainly in the posterior white columns. Obstruction of small intramedullary arteries and veins by the initial mechanical stress or secondary injury mechanisms most likely produced these extensive white matter lesions. Our studies implicate damage to the anterior sulcal arteries in causing the hemorrhagic necrosis and subsequent central myelomalacia at the injury site in acute spinal cord injury in humans.

Presence and significance of CD-95 (Fas/APO1) expression after spinal cord injury

2001 ◽  
Vol 94 (2) ◽  
pp. 257-264 ◽  
Author(s):  
Mercedes Zurita ◽  
Jesús Vaquero ◽  
Isabel Zurita
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
White Matter ◽  
Gray Matter ◽  
Spinal Cord Tissue ◽  
Injured Spinal Cord ◽  
Content Type ◽  
Cord Injury ◽  
Positive Immunostaining ◽  
Fine Print

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.

Physiologic Modulators of Neural Injury After Brain and Spinal Cord Injury

2017 ◽  
Author(s):  
W. Dalton Dietrich
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuronal Cell ◽  
Acute Injury ◽  
Secondary Injury ◽  
Edema Formation ◽  
Blood Brain Barrier Disruption ◽  
Injury Mechanisms ◽  
Cord Injury ◽  
Brain And Spinal Cord

Brain and spinal cord injury are leading causes of death and long-term disability, producing diverse burdens for the affected individuals, their families, and society. Such injuries, including traumatic brain injury, stroke, subarachnoid hemorrhage, and spinal cord injury, have common patterns of neuronal cell vulnerability that are associated with a complex cascade of pathologic processes that trigger the propagation of tissue damage beyond the acute injury. Secondary injury mechanisms, including oxidative stress, edema formation, changes in cerebral blood flow and vessel reactivity, metabolic and blood–brain barrier disruption, and neuroinflammation, are therefore important therapeutic targets. Several key physiological parameters require monitoring and intensive management during various phases of treatment to ameliorate secondary injury mechanisms and potentially protect against further neuronal injury. This chapter reviews the core physiological targets in the management of brain and spinal cord injury and relates them to secondary injury mechanisms and outcomes.

White matter changes in human spinal cord injury

1998 ◽  
pp. 395-407 ◽  
Author(s):  
B. A. Kakulas ◽  
R. L. Lorimer ◽  
A. D. Gubbay
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
White Matter ◽  
White Matter Changes ◽  
Human Spinal Cord ◽  
Cord Injury

Why Do We Not Have a Drug to Treat Acute Spinal Cord Injury?

Neurotrauma ◽  
2018 ◽  
pp. 411-422
Author(s):  
James W. Geddes
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Acute Spinal Cord Injury ◽  
Secondary Injury ◽  
Functional Deficits ◽  
Injury Mechanisms ◽  
Cord Injury ◽  
Contusion Injury ◽  
Weight Drop ◽  
Intraspinal Hemorrhage

More than 100 years ago, Alfred Reginald Allen developed the weight-drop model of graded, reproducible contusion injury to the dorsal spinal cord. Allen also introduced the concept of secondary injury mechanisms, hypothesizing that hemorrhage and elevated intraspinal pressure contribute to the destruction of the spinal cord and functional deficits. Our understanding of the secondary injury cascade has advanced tremendously over the past 100 years, with numerous therapeutic targets identified. Yet we lack an effective drug treatment for acute spinal cord injury. Reasons for the failure to translate promising preclinical findings to successful clinical trials include concerns regarding the quality of preclinical studies, including possible bias and inappropriate statistical analysis; questions regarding the suitability of animal models; and the complexity of secondary mechanisms following spinal cord injury. Perhaps, however, we have overlooked the targets identified by Allen, namely the intraspinal hemorrhage and elevations in intraspinal pressure.

scholarly journals Dorsal and ventral horn atrophy is associated with clinical outcome after spinal cord injury

Neurology ◽  
2018 ◽  
Vol 90 (17) ◽  
pp. e1510-e1522 ◽  
Author(s):  
Eveline Huber ◽  
Gergely David ◽  
Alan J. Thompson ◽  
Nikolaus Weiskopf ◽  
Siawoosh Mohammadi ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
White Matter ◽  
Clinical Outcome ◽  
Gray Matter ◽  
Ventral Horn ◽  
Tissue Specific ◽  
Weighted Sequence ◽  
Cord Injury ◽  
Lesion Severity

ObjectiveTo investigate whether gray matter pathology above the level of injury, alongside white matter changes, also contributes to sensorimotor impairments after spinal cord injury.MethodsA 3T MRI protocol was acquired in 17 tetraplegic patients and 21 controls. A sagittal T2-weighted sequence was used to characterize lesion severity. At the C2-3 level, a high-resolution T2*-weighted sequence was used to assess cross-sectional areas of gray and white matter, including their subcompartments; a diffusion-weighted sequence was used to compute voxel-based diffusion indices. Regression models determined associations between lesion severity and tissue-specific neurodegeneration and associations between the latter with neurophysiologic and clinical outcome.ResultsNeurodegeneration was evident within the dorsal and ventral horns and white matter above the level of injury. Tract-specific neurodegeneration was associated with prolonged conduction of appropriate electrophysiologic recordings. Dorsal horn atrophy was associated with sensory outcome, while ventral horn atrophy was associated with motor outcome. White matter integrity of dorsal columns and corticospinal tracts was associated with daily-life independence.ConclusionOur results suggest that, next to anterograde and retrograde degeneration of white matter tracts, neuronal circuits within the spinal cord far above the level of injury undergo transsynaptic neurodegeneration, resulting in specific gray matter changes. Such improved understanding of tissue-specific cord pathology offers potential biomarkers with more efficient targeting and monitoring of neuroregenerative (i.e., white matter) and neuroprotective (i.e., gray matter) agents.

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

2007 ◽  
Vol 6 (3) ◽  
pp. 255-266 ◽  
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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