Demyelination and Schwann cell responses adjacent to injury epicenter cavities following chronic human spinal cord injury

Guest, James D.; Hiester, Erik D.; Bunge, Richard P.

doi:10.1016/j.expneurol.2004.11.033

Cited by 275 publications

(228 citation statements)

References 66 publications

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“…The chronically injured human spinal cord also remains in a demyelinated or under-myelinated state (Guest et al 2005). After contusion injuries to the adult rat spinal cord, there is chronic progressive demyelination, suggesting that any myelin that is produced by either invading Schwann cells or oligodendrocytes is not stable (Totoiu and Kierstead, 2005).…”

Section: Discussionmentioning

confidence: 99%

Sensory afferents regenerated into dorsal columns after spinal cord injury remain in a chronic pathophysiological state

Tan

Petruska

Mendell

et al. 2007

Experimental Neurology

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Axon regeneration after experimental spinal cord injury (SCI) can be promoted by combinatorial treatments that increase the intrinsic growth capacity of the damaged neurons and reduce environmental factors that inhibit axon growth. A prior peripheral nerve conditioning lesion is a well established means of increasing the intrinsic growth state of sensory neurons whose axons project within the dorsal columns of the spinal cord. Combining such a prior peripheral nerve conditioning lesion with the infusion of antibodies that neutralize the growth-inhibitory effects of the NG2 chondroitin sulfate proteoglycan promotes sensory axon growth through the glial scar and into the white matter of the dorsal columns. The physiological properties of these regenerated axons, particularly in the chronic SCI phase, have not been established. Here we examined the functional status of regenerated sensory afferents in the dorsal columns after SCI. Six months post-injury, we located and electrically mapped functional sensory axons that had regenerated beyond the injury site. The regenerated axons had reduced conduction velocity, decreased frequency-following ability, and increasing latency to repetitive stimuli. Many of the axons that had regenerated into the dorsal columns rostral to the injury site were chronically demyelinated. These results demonstrate that regenerated sensory axons remain in a chronic pathophysiological state and emphasize the need to restore normal conduction properties to regenerated axons after spinal cord injury.

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Section: Discussionmentioning

confidence: 99%

Sensory afferents regenerated into dorsal columns after spinal cord injury remain in a chronic pathophysiological state

Tan

Petruska

Mendell

et al. 2007

Experimental Neurology

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“…This was confirmed in more recent work using tissue from dogs that had sustained a spontaneous SCI [43]. In human tissue, demyelinated axons have been detected to a variable degree along lesion borders from 1 to 22 years postinjury [9]. Thus, demyelination, especially acutely, appears to be a consistent finding after SCI and may contribute to functional deficits by abrogating action potential conduction through denuded segments.…”

Section: Demyelination and Remyelination After Scimentioning

confidence: 53%

“…Prolonged OL apoptosis has been detected for at least 3 weeks following rat spinal contusion; dying cells were especially prominent in degenerating axon tracts rostral and caudal to the injury site [3,8]. Apoptotic OLs have also been noted in tissue from nonhuman primates and human patients revealing that this phenomenon is common across multiple injury models and after human SCI [3,9,10].…”

Section: Spinal Cord Injury and Oligodendrocyte Lossmentioning

confidence: 96%

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Oligodendrocyte Fate after Spinal Cord Injury

2011

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Summary: Oligodendrocytes (OLs) are particularly susceptible to the toxicity of the acute lesion environment after spinal cord injury (SCI). They undergo both necrosis and apoptosis acutely, with apoptosis continuing at chronic time points. Loss of OLs causes demyelination and impairs axon function and survival. In parallel, a rapid and protracted OL progenitor cell proliferative response occurs, especially at the lesion borders. Proliferating and migrating OL progenitor cells differentiate into myelinating OLs, which remyelinate demyelinated axons starting at 2 weeks postinjury. The progression of OL lineage cells into mature OLs in the adult after injury recapitulates development to some degree, owing to the plethora of factors within the injury milieu. Although robust, this endogenous oligogenic response is insufficient against OL loss and demyelination. First, in this review we analyze the major spatial-temporal mechanisms of OL loss, replacement, and myelination, with the purpose of highlighting potential areas of intervention after SCI. We then discuss studies on OL protection and replacement. Growth factors have been used both to boost the endogenous progenitor response, and in conjunction with progenitor transplantation to facilitate survival and OL fate. Considerable progress has been made with embryonic stem cellderived cells and adult neural progenitor cells. For therapies targeting oligogenesis to be successful, endogenous responses and the effects of the acute and chronic lesion environment on OL lineage cells must be understood in detail, and in relation, the optimal therapeutic window for such strategies must also be determined.

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“…63 Similarly, Schwann cell invasion of the damaged spinal cord is uncommon in canine tissue, unless laceration of the meninges accompanies gross tissue destruction -again a finding that parallels those made in both rodent and human tissue. 64 Although the observable cellular responses at the light microscopic level have been well documented, the local and systemic immune responses to SCI have been little studied in canine patients, in contrast to the rapid advances in this field made in rodent SCI. 65 Therefore, the extent to which changes in immune status following canine SCI mimic those in rodents, or humans, is unclear at this time.…”

Section: Pathologymentioning

confidence: 99%

Clinical canine spinal cord injury provides an opportunity to examine the issues in translating laboratory techniques into practical therapy

et al. 2006

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Study design: Review. Objectives: To highlight the value of investigating the effects of putative therapeutic interventions in clinical spinal cord injury (SCI) in domestic dogs. Setting: England, UK. Methods: Many experimental interventions in laboratory rodents have been shown to ameliorate the functional deficits caused by SCI; the challenge now is to determine whether they can be translated into useful clinical techniques. Important differences between clinical SCI in human patients and that in laboratory rodents are in the size of the spinal cord and heterogeneity of injury severity. A further key issue is whether the statistical difference in outcome in the laboratory will translate into a useful difference in clinical outcome. Here, we stress the value of investigating the effects of putative therapies in clinical SCI in domestic dogs. The causes of injury, ability to categorise the severity and methods available to measure outcome are very similar between canine and human patients. Furthermore, postmortem tissue more rapidly becomes available from dogs because of their short lifespan than from human patients. Results: The role that investigation of canine SCI might play is illustrated by our preliminary trials on intraspinal transplantation of olfactory glial cells for severe SCI. Conclusions: This canine translational model provides a means of 'filtering' putative treatments before human application.

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Demyelination and Schwann cell responses adjacent to injury epicenter cavities following chronic human spinal cord injury

Cited by 275 publications

References 66 publications

Sensory afferents regenerated into dorsal columns after spinal cord injury remain in a chronic pathophysiological state

Sensory afferents regenerated into dorsal columns after spinal cord injury remain in a chronic pathophysiological state

Oligodendrocyte Fate after Spinal Cord Injury

Clinical canine spinal cord injury provides an opportunity to examine the issues in translating laboratory techniques into practical therapy

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