Deposition of Scar Tissue in the Central Nervous System

Berry, Martin; Maxwell, William L.; Logan, Ann; Mathewson, A.; McConnell, Patricia; Ashhurst, Doreen E.; Thomas, GD

doi:10.1007/978-3-7091-4147-2_3

Cited by 265 publications

(177 citation statements)

References 36 publications

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“…Collagen is produced in abundance by cells that infiltrate the injured spinal cord. In fact, the majority of the cells that comprise the post-SCI scar, including infiltrating meningeal fibroblasts (Berry et al 1983), endothelial cells (Schwab et al 2001), and astrocytes (Liesi and Kauppila 2002), express collagen. This dense collagen matrix forms the backbone of basal lamina sheets during the first week after SCI (Hermanns et al 2001) and is thought to act as a scaffold for blood vessel, fibroblast, and macrophage activity in the early lesion environment (Maxwell et al 1984).…”

Section: Generation Of Enhanced Populations Of Differentiated Progenymentioning

confidence: 99%

Region-specific Differentiation Potential of Adult Rat Spinal Cord Neural Stem/Precursors and Their Plasticity in Response to In Vitro Manipulation

Kulbatski

Tator

2009

J Histochem Cytochem.

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S U M M A R Y This study characterized the differentiation of neural stem/precursor cells (NSPCs) isolated from different levels of the spinal cord (cervical vs lumbar cord) and different regions along the neuraxis (brain vs cervical spinal cord) of adult male Wistar enhanced green fluorescent protein rats. The differentiation of cervical spinal cord NSPCs was further examined after variation of time in culture, addition of growth factors, and changes in cell matrix and serum concentration. Brain NSPCs did not differ from cervical cord NSPCs in the percentages of neurons, astrocytes, or oligodendrocytes but produced 26.9% less radial glia. Lumbar cord NSPCs produced 30.8% fewer radial glia and 6.9% more neurons compared with cervical cord NSPCs. Spinal cord NSPC differentiation was amenable to manipulation by growth factors and changes in in vitro conditions. This is the first study to directly compare the effect of growth factors, culturing time, serum concentration, and cell matrix on rat spinal cord NSPCs isolated, propagated, and differentiated under identical conditions. (J Histochem Cytochem 57:405-423, 2009)

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Section: Generation Of Enhanced Populations Of Differentiated Progenymentioning

confidence: 99%

Region-specific Differentiation Potential of Adult Rat Spinal Cord Neural Stem/Precursors and Their Plasticity in Response to In Vitro Manipulation

Kulbatski

Tator

2009

J Histochem Cytochem.

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“…In contrast to adult CNS injury, the presentation of astrogliosis is minimal after stab wounds to the embryonic or neonatal CNS (Bignami and Dahl, 1976;Berry et al, 1983;Maxwell et al, 1990). The minimal astrogliosis, however, becomes extensive when inflammatory cytokines, including IFN-␥, are administered locally to neonates at the time of stab wound injury (Balasingam et al, 1994).…”

Section: Abstract: Cns Trauma; Cytokines; Gliosis; Interleukin-1; Inmentioning

confidence: 99%

Astrogliosis in the Neonatal and Adult Murine Brain Post-Trauma: Elevation of Inflammatory Cytokines and the Lack of Requirement for Endogenous Interferon-γ

et al. 1997

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The relevance of astrogliosis remains controversial, especially with respect to the beneficial or detrimental influence of reactive astrocytes on CNS recovery. This dichotomy can be resolved if the mediators of astrogliosis are identified. We have measured the levels of transcripts encoding inflammatory cytokines in injury systems in which the presence or absence of astrogliosis could be produced selectively. A stab injury to the adult mouse brain using a piece of nitrocellulose (NC) membrane elicited a prompt and marked increase in levels of transcripts for interleukin (IL)-1α, IL-1β, and tumor necrosis factor (TNF)-α, which are considered to be microglia/macrophage cytokines. The elevations preceded, or occurred concomitantly with, the rise in glial fibrillary acidic protein mRNA, an early manifestation of astrogliosis. In neonatal mice, IL-1 and TNF-α mRNA were elevated to a greater extent by an NC-implant injury, which produced astrogliosis, than after an NC-stab, with minimal astrogliosis. We determined whether endogenous interferon (IFN)-γ could be responsible for the observed increases in IL-1 and TNF-α, because IFN-γ is a potent microglia/macrophage activator, and because its exogenous administration to rodents enhanced astrogliosis after adult or neonatal insults. A lack of requirement for endogenous IFN-γ was demonstrated by three lines of evidence. First, no increase in IFN-γ transcripts could be found at injury. Second, the administration of a neutralizing antibody to IFN-γ did not attenuate astrogliosis. Third, in IFN-γ knockout adult mice, astrogliosis and increases in levels of IL-1α and TNF-α were induced rapidly by injury. The marked elevation of inflammatory cytokines is discussed in the context of astrogliosis and general CNS recovery.

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“…Staining of sections taken from areas considered positive for schwannosis in PPD-stained plastic sections were negative for the presence of Schwann cells. We speculate that instead these structures are primarily composed of fibroblasts (i.e., mesenchymal-derived), similar to the mesenchymal scar described in human spinal cord injury patients, primarily after a laceratingtype of injury (Berry et al, 1983;Norenberg et al, 2004).…”

Section: Figmentioning

confidence: 65%

Chronic Spinal Compression Model in Minipigs: A Systematic Behavioral, Qualitative, and Quantitative Neuropathological Study

Navarro

Juhás²,

Keshavarzi³

et al. 2012

Journal of Neurotrauma

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The goal of the present study was to develop a porcine spinal cord injury (SCI) model, and to describe the neurological outcome and characterize the corresponding quantitative and qualitative histological changes at 4-9 months after injury. Adult Gottingen-Minnesota minipigs were anesthetized and placed in a spine immobilization frame. The exposed T12 spinal segment was compressed in a dorso-ventral direction using a 5-mmdiameter circular bar with a progressively increasing peak force (1.5, 2.0, or 2.5 kg) at a velocity of 3 cm/sec. During recovery, motor and sensory function were periodically monitored. After survival, the animals were perfusion fixed and the extent of local SCI was analyzed by (1) post-mortem MRI analysis of dissected spinal cords, (2) qualitative and quantitative analysis of axonal survival at the epicenter of injury, and (3) defining the presence of local inflammatory changes, astrocytosis, and schwannosis. Following 2.5-kg spinal cord compression the animals demonstrated a near complete loss of motor and sensory function with no recovery over the next 4-9 months. Those that underwent spinal cord compression with 2 kg force developed an incomplete injury with progressive partial neurological recovery characterized by a restricted ability to stand and walk. Animals injured with a spinal compression force of 1.5 kg showed near normal ambulation 10 days after injury. In fully paralyzed animals (2.5 kg), MRI analysis demonstrated a loss of spinal white matter integrity and extensive septal cavitations. A significant correlation between the magnitude of loss of small and medium-sized myelinated axons in the ventral funiculus and neurological deficits was identified. These data, demonstrating stable neurological deficits in severely injured animals, similarities of spinal pathology to humans, and relatively good post-injury tolerance of this strain of minipigs to spinal trauma, suggest that this model can successfully be used to study therapeutic interventions targeting both acute and chronic stages of SCI.

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Deposition of Scar Tissue in the Central Nervous System

Cited by 265 publications

References 36 publications

Region-specific Differentiation Potential of Adult Rat Spinal Cord Neural Stem/Precursors and Their Plasticity in Response to In Vitro Manipulation

Region-specific Differentiation Potential of Adult Rat Spinal Cord Neural Stem/Precursors and Their Plasticity in Response to In Vitro Manipulation

Astrogliosis in the Neonatal and Adult Murine Brain Post-Trauma: Elevation of Inflammatory Cytokines and the Lack of Requirement for Endogenous Interferon-γ

Chronic Spinal Compression Model in Minipigs: A Systematic Behavioral, Qualitative, and Quantitative Neuropathological Study

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