Reactions of Oligodendrocytes to Spinal Cord Injury: Cell Survival and Myelin Repair

Frei, Eveline; Klusman, Isabel; Schnell, Lisa; Schwab, Martin E.

doi:10.1006/exnr.2000.7379

Cited by 46 publications

(32 citation statements)

References 36 publications

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“…44 On the other hand, some authors propose that oligodendrocytes are rather resistant to the presence of inflammatory cells in the spinal cord, suggesting that activated macrophages and microglia are able to distinguish intact oligodendrocytes and myelin and destroy only the degenerating myelin. 45 In accord with that observation, activated macrophages and microglia were observed over a large part of the striatum in our study, but the demyelination was largely confined to the center of the lesion. Only further experiments will allow for better dissecting the role of IL-1 per se or the inflammatory infiltrate and associated mediators on the demyelination observed.…”

Section: Il-1 and Demyelinationsupporting

confidence: 92%

Reversible Demyelination, Blood-Brain Barrier Breakdown, and Pronounced Neutrophil Recruitment Induced by Chronic IL-1 Expression in the Brain

Ferrari

Depino

Prada

et al. 2004

The American Journal of Pathology

187

149

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Interleukin-1␤ (IL-1) expression is associated with a spectrum of neuroinflammatory processes related to chronic neurodegenerative diseases. The single-bolus microinjection of IL-1 into the central nervous system (CNS) parenchyma gives rise to delayed and localized neutrophil recruitment, transient blood-brain barrier (BBB) breakdown, but no overt damage to CNS integrity. However, acute microinjections of IL-1 do not mimic the chronic IL-1 expression, which is a feature of many CNS diseases. To investigate the response of the CNS to chronic IL-1 expression, we injected a recombinant adenovirus expressing IL-1 into the striatum. At the peak of IL-1 expression (days 8 and 14 post-injection), there was a marked recruitment of neutrophils, vasodilatation, and breakdown of the BBB. Microglia and astrocyte activation was evident during the first 14 days post-injection. At days 8 and 14, extensive demyelination was observed but the number of neurons was not affected by any treatment. Finally, at 30 days, signs of inflammation were no longer present, there was evidence of tissue reorganization, the BBB was intact, and the process of remyelination was noticeable. In summary, our data show that chronic expression of IL-1, in contrast to its acute delivery, can reversibly damage CNS integrity and implicates this cytokine or downstream components as major mediators of demyelination in chronic inflammatory and demyelinating diseases.

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Section: Il-1 and Demyelinationsupporting

confidence: 92%

Reversible Demyelination, Blood-Brain Barrier Breakdown, and Pronounced Neutrophil Recruitment Induced by Chronic IL-1 Expression in the Brain

Ferrari

Depino

Prada

et al. 2004

The American Journal of Pathology

187

149

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“…NG2 cells have been shown previously to proliferate and migrate toward and into damaged tissue (Chari and Blakemore, 2002;Hampton et al, 2004;Levine and Reynolds, 1999;Watanabe et al, 2002), which suggests that lesioned environments emit tropic signals for these cells. Other studies have also shown that OL numbers rise outside a variety of CNS lesions (Frei et al, 2000;Gard and Pfeiffer, 1990;Mandai et al, 1997). Thus, NG2 cell accumulation and oligodendrogenesis may be a general response to factors released by dying cells, exposed axons, reactive astrocytes, and/or infiltrating inflammatory cells.…”

Section: Discussionmentioning

confidence: 92%

Prominent oligodendrocyte genesis along the border of spinal contusion lesions

Tripathi

McTigue

2007

Glia

122

148

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Oligodendrocyte (OL) loss and axon demyelination occur after spinal cord injury (SCI). OLs may be replaced, however, by proliferating NG2+ progenitor cells. Indeed, new OLs have been noted in ventral white matter after SCI. Since tissue adjacent to lesion cavities is exposed to different mediators compared with outlying spared tissue, the authors used a rat SCI model to compare NG2 cell proliferation and OL genesis adjacent to lesion cavities with that in spared tissue closer to meninges. NG2 cells proliferated throughout the first week postinjury and accumulated along lesion borders, especially within gray matter. By 3 days postinjury (dpi), new OLs were detected throughout the cross-sections; between 4 and 7 dpi, however, oligogenesis was restricted to lesion borders. New OLs derived from cells proliferating during 1-7 dpi increased dramatically by 14 dpi; most were located along lesion borders and in spared gray matter. Oligogenesis continued along lesion borders during the second week postinjury. Overall OL numbers were reduced at 3 dpi in spared tissue, but rebounded to normal levels by 14 dpi. Surprisingly, lesion borders maintained normal OL numbers at 3 dpi, which then rose to exceed preinjury levels at 7 and 14 dpi. These results indicate that oligogenesis is protracted after SCI and leads to increased OL numbers. Most new OLs are formed in regions of greatest NG2 cell proliferation. Thus, the adult spinal cord spontaneously develops a dynamic gliogenic zone along lesion borders.

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“…Furthermore, myelin-associated inhibitors may not be available to interact with sprouting axons and inhibit their regeneration as a result of the death of oligodendrocytes after spinal cord injury (SCI) and the rapid clearance of myelin debris by macrophages (Frei et al, 2000;McTigue et al, 2001;Zai and Wrathall, 2005). Despite the increased expression of semaphorins after SCI (Pasterkamp et al, 1999;Frei et al, 2000;Zai and Wrathall, 2005), there is no functional or genetic evidence that these molecules play an inhibitory role.…”

Section: Introductionmentioning

confidence: 99%

Antibodies against the NG2 Proteoglycan Promote the Regeneration of Sensory Axons within the Dorsal Columns of the Spinal Cord

Tan¹,

Colletti²,

Rorai³

et al. 2006

J. Neurosci.

125

138

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The NG2 chondroitin sulfate proteoglycan inhibits axon growth in vitro. Levels of NG2 increase rapidly in the glial scars that form at sites of CNS injury, suggesting that NG2 may inhibit axon regeneration. To determine the functions of NG2, we infused mixtures of neutralizing or non-neutralizing anti-NG2 monoclonal antibodies into the dorsally transected adult rat spinal cord and analyzed the regeneration of ascending mechanosensory axons anatomically. At 1 week after injury, ascending sensory axons in control animals terminated caudal to the lesion within an area containing dense deposits of NG2 immunoreactivity. In animals treated with the neutralizing anti-NG2 antibodies, labeled axons penetrated the caudal border of the lesion and grew into and beyond the lesion center. The low intrinsic growth capacity of adult neurons may also limit the ability of damaged axons to regenerate. To enhance growth, we combined antibody treatment with a peripheral nerve conditioning lesion. After a conditioning lesion and treatment with control, non-neutralizing antibodies, many sensory axons grew into the lesion core. These axons did not grow past the rostral border of the lesion; rather, they grew along the dorsal surface of the spinal cord and within any remaining pieces of the dorsal roots. In contrast, combining a peripheral nerve conditioning lesion with neutralizing anti-NG2 antibodies resulted in sensory axon regeneration past the glial scar and into the white matter rostral to the injury site. The combinatorial approach used here that neutralizes extrinsic inhibition and increases intrinsic growth results in anatomically correct axon regeneration, a prerequisite for functional recovery.

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Reactions of Oligodendrocytes to Spinal Cord Injury: Cell Survival and Myelin Repair

Cited by 46 publications

References 36 publications

Reversible Demyelination, Blood-Brain Barrier Breakdown, and Pronounced Neutrophil Recruitment Induced by Chronic IL-1 Expression in the Brain

Reversible Demyelination, Blood-Brain Barrier Breakdown, and Pronounced Neutrophil Recruitment Induced by Chronic IL-1 Expression in the Brain

Prominent oligodendrocyte genesis along the border of spinal contusion lesions

Antibodies against the NG2 Proteoglycan Promote the Regeneration of Sensory Axons within the Dorsal Columns of the Spinal Cord

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