Endogenous Repair after Spinal Cord Contusion Injuries in the Rat

Beattie, Michael S.; Bresnahan, Jacqueline C.; Komon, J.; Tovar, C. Amy; Meter, Mijo; Anderson, Douglas K.; Ai, Faden; Hsu, Chung Y.; Noble, Linda; Salzman, Steven K.; Young, Wise

doi:10.1006/exnr.1997.6695

Cited by 366 publications

(281 citation statements)

References 38 publications

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“…Concomitantly, labeling with BrdU detected dividing ependymal cells (Fig. 2 E) (Beattie et al, 1997;Johansson et al, 1999;Namiki and Tator 1999). The expression of pVim (Kamei et al, 1998) also indicated cell divisions in the ependymal layer (Fig.…”

Section: Expression Of Specific Transcription Factors In Vivomentioning

confidence: 78%

Transcription Factor Expression and Notch-Dependent Regulation of Neural Progenitors in the Adult Rat Spinal Cord

Yamamoto¹,

Nagao²,

Sugimori³

et al. 2001

J. Neurosci.

230

199

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Recent studies have demonstrated that neural stem cells and other progenitors are present in the adult CNS. Details of their properties, however, remain poorly understood. Here we examined the properties and control mechanisms of neural progenitors in the adult rat spinal cord at the molecular level. Adult and embryonic progenitors commonly expressed various homeodomain-type (Pax6, Pax7, Nkx2.2, and Prox1) and basic helix-loop-helix (bHLH)-type (Ngn2, Mash1, NeuroD1, and Olig2) transcriptional regulatory factors in vitro. Unlike their embryonic counterparts, however, adult progenitors could not generate specific neurons that expressed markers appropriate for spinal motoneurons or interneurons, including Islet1, Lim1, Lim3, and HB9. Cells expressing the homeodomain factors Pax6, Pax7, and Nkx2.2 also emerged in vivo in response to injury and were distributed in unique patterns in the lesioned spinal cord. However, neither the expression of the neurogenic bHLH factors including Ngn2, Mash1, and NeuroD1 nor subsequent generation of new neurons could be detected in injured tissue. Our results suggest that signaling through the cellsurface receptor Notch is involved in this restriction. The expression of Notch1 in vivo was enhanced in response to injury. Furthermore, activation of Notch signaling in vitro inhibited differentiation of adult progenitors, whereas attenuation of Notch signals and forced expression of Ngn2 significantly enhanced neurogenesis. These results suggest that both the intrinsic properties of adult progenitors and local environmental signals, including Notch signaling, account for the limited regenerative potential of the adult spinal cord.

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Section: Expression Of Specific Transcription Factors In Vivomentioning

confidence: 78%

Transcription Factor Expression and Notch-Dependent Regulation of Neural Progenitors in the Adult Rat Spinal Cord

Yamamoto¹,

Nagao²,

Sugimori³

et al. 2001

J. Neurosci.

230

199

View full text Add to dashboard Cite

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“…We and others have shown that ependymal cells The adult mammalian central nervous system contains endogenous stem/progenitor cells that are selflining the central canal of the spinal cord of adult rodents proliferate in response to several types of trauma renewing and multipotent, capable of generating both neurons and glia. Stem/progenitor cells have been iden- (4,14,17,25,29,30,42,44) or intrathecal administration of mitogenic growth factors (16,19). In lower vertebrates, tified in the adult rat and mouse spinal cord (14,15,17,24,(28)(29)(30)36,46,47).…”

Section: Introductionmentioning

confidence: 99%

Adult Spinal Cord Stem/Progenitor Cells Transplanted as Neurospheres Preferentially Differentiate into Oligodendrocytes in the Adult Rat Spinal Cord

et al. 2008

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Neural stem/progenitor cells (NSPCs) capable of generating new neurons and glia reside in the adult mammalian spinal cord. Transplantation of NSPCs has therapeutic potential for spinal cord injury, although there is limited information on the ability of these cells to survive and differentiate in vivo. Neurospheres cultured from the periventricular region of the adult spinal cord contain NSPCs that are self-renewing and multipotent. We examined the survival, proliferation, migration, and differentiation of adult spinal cord NSPCs generated from green fluorescent protein (GFP) transgenic rats and transplanted into the intact spinal cord. The grafted GFP-expressing cells survived for at least 6 weeks in vivo and migrated from the injection site along the rostro-caudal axis of the spinal cord. Transplanted cells transiently proliferated following transplantation and approximately 17% of the GFP-positive cells were apoptotic at 1 day. Also, better survival was seen with NSPCs transplanted as neurospheres in comparison to NSPCs transplanted as dissociated cells. By 1 week posttransplantation, grafted cells primarily expressed an oligodendrocytic phenotype and only 2% differentiated into astrocytes. Approximately 75% versus 38% of the grafted cells differentiated into oligodendrocytes after transplantation into spinal white versus gray matter, respectively. This is the first report to examine the time course of cell survival, proliferation, apoptosis, and phenotypic differentiation of transplanted NSPSs in the spinal cord. This is also the first report to examine the differences between transplanted NSPCs grafted as neurospheres or dissociated cells, and to compare the differentiation potential after transplantation into spinal cord white versus gray matter.

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“…Commonly, a fluid-filled cyst is the final consequence of this process (Balentine, 1978;Wozniewicz et al, 1983;Kakulas, 1984;Bresnahan et al, 1991;Bunge et al, 1993;Ito et al, 1997;Norenburg et al, 2004). Because of the lack of a solid substrate, this late-stage pathological endpoint represents a physical gap that impedes axonal regeneration and functional recovery (Guth et al, 1985;Basso et al, 1996;Beattie et al, 1997). To guide regenerating axons across this cavity, several research groups have investigated the use of bridging materials that include substrates derived from either stem cells (McDonald et al, 1999;Akiyama et al, 2002), support cells (Xu et al, 1995;Li et al, 1997), autologous grafts (von Wild and Brunelli, 2003;Houle et al, 2006), embryonic grafts (Reier et al, 1986), natural substances (Marchand et al, 1993), or synthetic substances (Tsai et al, 2004;Wen and Tresco, 2006).…”

Section: Introductionmentioning

confidence: 99%

Evaluating neuronal and glial growth on electrospun polarized matrices: bridging the gap in percussive spinal cord injuries

et al. 2007

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One of the many obstacles to spinal cord repair following trauma is the formation of a cyst that impedes axonal regeneration. Accordingly, we examined the potential use of electrospinning to engineer an implantable polarized matrix for axonal guidance. Polydioxanone, a resorbable material, was electrospun to fabricate matrices possessing either aligned or randomly oriented fibers. To assess the extent to which fiber alignment influences directional neuritic outgrowth, rat dorsal root ganglia (DRGs) were cultured on these matrices for 10 days. Using confocal microscopy, neurites displayed a directional growth that mimicked the fiber alignment of the underlying matrix. Because these matrices are generated from a material that degrades with time, we next determined whether a glial substrate might provide a more stable interface between the resorbable matrix and the outgrowing axons. Astrocytes seeded onto either aligned or random matrices displayed a directional growth pattern similar to that of the underlying matrix. Moreover, these glia-seeded matrices, once cocultured with DRGs, conferred the matrix alignment to and enhanced outgrowth exuberance of the extending neurites. These experiments demonstrate the potential for electrospinning to generate an aligned matrix that influences both the directionality and growth dynamics of DRG neurites.

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Endogenous Repair after Spinal Cord Contusion Injuries in the Rat

Cited by 366 publications

References 38 publications

Transcription Factor Expression and Notch-Dependent Regulation of Neural Progenitors in the Adult Rat Spinal Cord

Transcription Factor Expression and Notch-Dependent Regulation of Neural Progenitors in the Adult Rat Spinal Cord

Adult Spinal Cord Stem/Progenitor Cells Transplanted as Neurospheres Preferentially Differentiate into Oligodendrocytes in the Adult Rat Spinal Cord

Evaluating neuronal and glial growth on electrospun polarized matrices: bridging the gap in percussive spinal cord injuries

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