Erythropoietin-mediated preservation of the white matter in rat spinal 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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The effects of methylprednisolone and the ganglioside GM1 on acute spinal cord injury in rats

Journal of Neurosurgery ◽

10.3171/jns.1994.80.1.0097 ◽

1994 ◽

Vol 80 (1) ◽

pp. 97-111 ◽

Cited By ~ 248

Author(s):

Shlomo Constantini ◽

Wise Young

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Body Weight Loss ◽

Ganglioside Gm1 ◽

Rat Spinal Cord ◽

Neuroprotective Effects ◽

Content Type ◽

Human Spinal Cord ◽

Cord Injury ◽

Fine Print

✓ Recent clinical trials have reported that methylprednisolone sodium succinate (MP) or the monosialic ganglioside GM1 improves neurological recovery in human spinal cord injury. Because GM1 may have additive or synergistic effects when used with MP, the authors compared MP, GM1, and MP+GM1 treatments in a graded rat spinal cord contusion model. Spinal cord injury was caused by dropping a rod weighing 10 gm from a height of 1.25, 2.5, or 5.0 cm onto the rat spinal cord at T-10, which had been exposed via laminectomy. The lesion volumes were quantified from spinal cord Na and K shifts at 24 hours after injury and the results were verified histologically in separate experiments. A single dose of MP (30 mg/kg), given 5 minutes after injury, reduced 24-hour spinal cord lesion volumes by 56% (p = 0.0052), 28% (p = 0.0065), and 13% (p > 0.05) in the three injury-severity groups, respectively, compared to similarly injured control groups treated with vehicle only. Methylprednisolone also prevented injury-induced hyponatremia and increased body weight loss in the spine-injured rats. When used alone, GM1 (10 to 30 mg/kg) had little or no effect on any measured variable compared to vehicle controls; when given concomitantly with MP, GM1 blocked the neuroprotective effects of MP. At a dose of 3 mg/kg, GM1 partially prevented MP-induced reductions in lesion volumes, while 10 to 30 mg/kg of GM1 completely blocked these effects of MP. The effects of MP on injury-induced hyponatremia and body weight loss were also blocked by GM1. Thus, GM1 antagonized both central and peripheral effects of MP in spine-injured rats. Until this interaction is clarified, the authors recommend that MP and GM1 not be used concomitantly to treat acute human spinal cord injury. Because GM1 modulates protein kinase activity, protein kinases inhibit lipocortins, and lipocortins mediate anti-inflammatory effects of glucocorticoids, it is proposed that the neuroprotective effects of MP are partially due to anti-inflammatory effects and that GM1 antagonizes the effects of MP by inhibiting lipocortin. Possible beneficial effects of GM1 reported in central nervous system injury may be related to the effects on neural recovery rather than acute injury processes.

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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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