Differential Cellular Accumulation of Connective Tissue Growth Factor Defines a Subset of Reactive Astrocytes, Invading Fibroblasts, and Endothelial Cells Following Central Nervous System Injury in Rats           and Humans

Inhibition of the small GTPase ras homology protein (Rho) or its downstream target, the Rho-associated kinase (ROCK), has been shown to promote axon regeneration and to improve functional recovery following spinal cord injury (SCI) in the adult rat. Here, we have analyzed the expression of RhoA and RhoB following spinal cord injury in order to assess whether Rho is a possible target for late pharmacological intervention. In control spinal cords, RhoA(+) cells were almost absent, whereas RhoB was localized to some ependymal cells, a few microglia, and some dissociated neurons. In injured spinal cords, RhoA(+) and RhoB(+)cells accumulated at perilesional areas and in the developing necrotic core early after injury at day 1. After reaching their maximum levels (RhoA at day 3; RhoB at day 1), RhoA(+) and RhoB(+) cell numbers remained significantly elevated until day 28. In areas remote from the lesion (> or =0.75 mm), a more discrete accumulation of RhoA(+) and RhoB(+) cells was observed, primarily in areas of ongoing Wallerian degeneration. RhoA and RhoB were predominantly expressed by polymorphonuclear granulocytes, ED1(+) microglia/macrophages, oligodendrocytes, some neurons, and swollen axons/neurites. Furthermore, expression was located to lesional, reactive astrocytes and fibroblastoid cells confined to areas of scar formation. Our experiments have determined that most RhoA(+) and RhoB(+) cells (>70%) are of mononuclear origin. The persistent presence of lesional RhoA(+) and RhoB(+) axon/neurite fibers over a period of 4 weeks after injury suggests that Rho inhibition is a putative therapeutic concept also for delayed intervention after SCI.

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“…2J). RhoA ϩ fibroblastoid cells resembled GFAP Ϫ , vimentin ϩ cells as described earlier (Schwab et al, 2001b).…”

Section: Expression Of Rhoa Following Scisupporting

confidence: 64%

Prolonged lesional expression of RhoA and RhoB following spinal cord injury

et al. 2005

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“…Nestin expression has also been shown in radial glial cells, ependymal cells, and in reactive astrocytes after CNS injury in rats. [28][29][30] In previous studies of NSC transplantation in adult rat models of SCI, NSCs have primarily differentiated into astrocytes or remained undifferentiated. 20,31,32 This is in contrast to our findings that show no differentiation into GFAP-expressing cells within the channels.…”

Section: Discussionmentioning

confidence: 99%

Neural Stem Cell– and Schwann Cell–Loaded Biodegradable Polymer Scaffolds Support Axonal Regeneration in the Transected Spinal Cord

Olson

Rooney

Gross

et al. 2009

Tissue Engineering Part A

152

143

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Biodegradable polymer scaffolds provide an excellent approach to quantifying critical factors necessary for restoration of function after a transection spinal cord injury. Neural stem cells (NSCs) and Schwann cells (SCs) support axonal regeneration. This study examines the compatibility of NSCs and SCs with the poly-lacticco-glycolic acid polymer scaffold and quantitatively assesses their potential to promote regeneration after a spinal cord transection injury in rats. NSCs were cultured as neurospheres and characterized by immunostaining for nestin (NSCs), glial fibrillary acidic protein (GFAP) (astrocytes), bIII-tubulin (immature neurons), oligodendrocyte-4 (immature oligodendrocytes), and myelin oligodendrocyte (mature oligodendrocytes), while SCs were characterized by immunostaining for S-100. Rats with transection injuries received scaffold implants containing NSCs (n ¼ 17), SCs (n ¼ 17), and no cells (control) (n ¼ 8). The degree of axonal regeneration was determined by counting neurofilament-stained axons through the scaffold channels 1 month after transplantation. Serial sectioning through the scaffold channels in NSC-and SC-treated groups revealed the presence of nestin, neurofilament, S-100, and bIII tubulin-positive cells. GFAP-positive cells were only seen at the spinal cord-scaffold border. There were significantly more axons in the NSC-and SC-treated groups compared to the control group. In conclusion, biodegradable scaffolds with aligned columns seeded with NSCs or SCs facilitate regeneration across the transected spinal cord. Further, these multichannel biodegradable polymer scaffolds effectively serve as platforms for quantitative analysis of axonal regeneration.

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“…Ctgf is involved in diverse processes in the nervous system, which include angiogenesis, fibrotic and glial scarring, and extracellular matrix remodeling in normal and injured tissue (Hertel et al, 2000;Schwab et al, 2001). Timp2 is also involved in tissue remodeling as the inhibitory part of a matrix metalloproteinase complex.…”

Section: Discussionmentioning

confidence: 99%

Genetic expression profile of olfactory ensheathing cells is distinct from that of Schwann cells and astrocytes

Vincent

Taylor

Choi-Lundberg

et al. 2005

Glia

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Olfactory ensheathing cells (OECs) accompany the axons of olfactory receptor neurons, which regenerate throughout life, from the olfactory mucosa into the olfactory bulb. OECs have shown widely varying efficacy in repairing the injured nervous system. Analysis of the transcriptome of OECs will help in understanding their biology and will provide tools for investigating the mechanisms of their efficacy and interactions with host tissues in lesion models. In this study, we compared the transcriptional profile of cultured OECs with that of Schwann cells (SCs) and astrocytes (ACs), two glial cell types to which OECs have similarities. Two biological replicates of RNA from cultured OECs, SCs, and ACs were hybridized to long oligo rat 5K arrays against a common reference pool of RNA (50% cultured fibroblast RNA and 50% neonatal rat brain RNA). Transcriptional profiles were analyzed by hierarchical clustering, Principal Components Analysis, and the Venn diagram. The three glial cell types had similarly increased or decreased expression of numerous transcripts compared with the reference. However, OECs were distinguishable from both SCs and ACs by a modest number of transcripts, which were significantly enriched or depleted. Furthermore, OECs and SCs were more closely related to each other than to ACs. Expression of selected transcripts not previously characterized in OECs, such as Lyz, Timp2, Gro1 (Cxcl1), Ccl2 (MCP1), Ctgf, and Cebpb, was validated by real-time reverse transcription-polymerase chain reaction (RT-PCR); immunohistochemistry in cultured OECs, SCs, and ACs, and adult tissues was performed to demonstrate their expression at the protein level.

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Differential Cellular Accumulation of Connective Tissue Growth Factor Defines a Subset of Reactive Astrocytes, Invading Fibroblasts, and Endothelial Cells Following Central Nervous System Injury in Rats and Humans

Cited by 93 publications

References 38 publications

Prolonged lesional expression of RhoA and RhoB following spinal cord injury

Prolonged lesional expression of RhoA and RhoB following spinal cord injury

Neural Stem Cell– and Schwann Cell–Loaded Biodegradable Polymer Scaffolds Support Axonal Regeneration in the Transected Spinal Cord

Genetic expression profile of olfactory ensheathing cells is distinct from that of Schwann cells and astrocytes

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