Effects of axon degeneration on oligodendrocyte lineage cells: Dorsal rhizotomy evokes a repair response while axon degeneration rostral to spinal contusion induces both repair and apoptosis

Sun, Fang; Lin, Chien‐liang Glenn; McTigue, Dana M.; Shan, Xiu; Tovar, C. Amy; Bresnahan, Jacqueline C.; Beattie, Michael S.

doi:10.1002/glia.21009

Cited by 35 publications

(38 citation statements)

References 92 publications

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“…One explanation for this difference is the unique oxidative microenvironment created by spinal contusion may prevent maximal proliferation. For example,Sun et al (2010) showed that RNA oxidation is significantly increased in oligodendrocytes near contusion injuries within 1h but oxidation was not present around pure axon degeneration injuries. In our study, contusion tissue supported later OPC division since NG2/BrdU cells increased 9-fold between 1 – 7dpi.…”

Section: Discussionmentioning

confidence: 99%

Changes in NG2 cells and oligodendrocytes in a new model of intraspinal hemorrhage

Sahinkaya

Milich

McTigue

2014

Experimental Neurology

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Spinal cord injury (SCI) evokes rapid deleterious and reparative glial reactions. Understanding the triggers for these responses is necessary for designing strategies to maximize repair. This study examined lesion formation and glial responses to vascular disruption and hemorrhage, a prominent feature of acute SCI. The specific role of hemorrhage is difficult to evaluate in trauma-induced lesions, because mechanical injury initiates many downstream responses. To isolate vascular disruption from trauma-induced effects, we created a novel and reproducible model of collagenase-induced intraspinal hemorrhage (ISH) and compared glial reactions between unilateral ISH and a hemi-contusion injury. Similar to contusion injuries, ISH lesions caused loss of myelin and axons and became filled with iron-laden macrophages. We hypothesized that intraspinal hemorrhage would also initiate reparative cellular responses including NG2+ oligodendrocyte progenitor cell (OPC) proliferation and oligodendrocyte genesis. Indeed, ISH induced OPC proliferation within 1d post-injury (dpi), which continued throughout the first week and resulted in a sustained elevation of NG2+ OPCs. ISH also caused oligodendrocyte loss within 4h that was sustained through 3d post-ISH. However, oligodendrogenesis, as determined by bromo-deoxyuridine (BrdU) positive oligodendrocytes, restored oligodendrocyte numbers by 7dpi, revealing that proliferating OPCs differentiated into new oligodendrocytes after ISH. The signaling molecules pERK1/2 and pSTAT3 were robustly increased acutely after ISH, with pSTAT3 being expressed in a portion of OPCs, suggesting that activators of this signaling cascade may initiate OPC responses. Aside from subtle differences in timing of OPC responses, changes in ISH tissue closely mimicked those in hemi-contusion tissue. These results are important for elucidating the contribution of hemorrhage to lesion formation and endogenous cell-mediated repair, and will provide the foundation for future studies geared toward identifying the role of specific blood components on injury and repair mechanisms. This understanding may provide new clinical targets for SCI and other devastating conditions such as intracerebral hemorrhage.

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Section: Discussionmentioning

confidence: 99%

Changes in NG2 cells and oligodendrocytes in a new model of intraspinal hemorrhage

Sahinkaya

Milich

McTigue

2014

Experimental Neurology

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“…To observe the dynamic changes occurring in mature oligodendrocytes during epileptogenesis, immunohistochemistry was used to study the expression of CC1, a marker of mature oligodendrocytes (Flygt et al, 2013;Sun et al, 2010). Fig.…”

Section: Oligodendrocytes In Rats Subjected To Lithiumpilocarpine-indmentioning

confidence: 99%

Alterations in hippocampal myelin and oligodendrocyte precursor cells during epileptogenesis

Luo

Zhang

et al. 2015

Brain Research

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“…In rodents, this diminution of OLs occurs several segments away from the epicenter, extending rostro-caudally along the degenerating axon tracts [6,8]. However, a recent study determined that axon degeneration alone (in the absence of trauma) was not sufficient to kill OLs and in fact evoked OPC proliferation and new OL formation [30]. The authors contrasted this response to OL apoptosis rostral to spinal contusion in which they noted that markers of oxidative stress were present in OLs following contusion injury but not dorsal rhizotomy.…”

Section: Early Mechanisms Of Ol Lossmentioning

confidence: 99%

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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Effects of axon degeneration on oligodendrocyte lineage cells: Dorsal rhizotomy evokes a repair response while axon degeneration rostral to spinal contusion induces both repair and apoptosis

Cited by 35 publications

References 92 publications

Changes in NG2 cells and oligodendrocytes in a new model of intraspinal hemorrhage

Changes in NG2 cells and oligodendrocytes in a new model of intraspinal hemorrhage

Alterations in hippocampal myelin and oligodendrocyte precursor cells during epileptogenesis

Oligodendrocyte Fate after Spinal Cord Injury

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