Resident Neural Stem Cells Restrict Tissue Damage and Neuronal Loss After Spinal Cord Injury in Mice

Sabelström, Hanna; Stenudd, Moa; Réu, Pedro; Dias, David O.; Elfineh, Marta; Zdunek, Sofia; Damberg, Peter; Göritz, Christian; Frisén, Jonas

doi:10.1126/science.1242576

Cited by 241 publications

(294 citation statements)

References 27 publications

Supporting

Mentioning

279

Contrasting

Unclassified

Order By: Relevance

“…Intriguingly, some of this glial progeny derived from SEZ NSCs after injury becomes migratory toward the injury site (Benner et al, 2013), while local reactive astrocytes in the cerebral cortex GM do not migrate (Bardehle et al, 2013). NSC‐derived reactive astrocytes may exert beneficial functions in the injury site (Sabelström et al 2013), further emphasizing the significance of comparing the properties and molecular signature of endogenous adult NSCs with those of reactive astrocytes (for review, see Götz et al, 2015; Grégoire et al, 2015; Robel et al, 2011; Silver and Steindler, 2009). …”

Section: Discussionmentioning

confidence: 99%

Astrocyte reactivity after brain injury—: The role of galectins 1 and 3

Sirko

Irmler

Gascón

et al. 2015

Glia

109

View full text Add to dashboard Cite

Astrocytes react to brain injury in a heterogeneous manner with only a subset resuming proliferation and acquiring stem cell properties in vitro. In order to identify novel regulators of this subset, we performed genomewide expression analysis of reactive astrocytes isolated 5 days after stab wound injury from the gray matter of adult mouse cerebral cortex. The expression pattern was compared with astrocytes from intact cortex and adult neural stem cells (NSCs) isolated from the subependymal zone (SEZ). These comparisons revealed a set of genes expressed at higher levels in both endogenous NSCs and reactive astrocytes, including two lectins—Galectins 1 and 3. These results and the pattern of Galectin expression in the lesioned brain led us to examine the functional significance of these lectins in brains of mice lacking Galectins 1 and 3. Following stab wound injury, astrocyte reactivity including glial fibrillary acidic protein expression, proliferation and neurosphere‐forming capacity were found significantly reduced in mutant animals. This phenotype could be recapitulated in vitro and was fully rescued by addition of Galectin 3, but not of Galectin 1. Thus, Galectins 1 and 3 play key roles in regulating the proliferative and NSC potential of a subset of reactive astrocytes. GLIA 2015;63:2340–2361

show abstract

Section: Discussionmentioning

confidence: 99%

Astrocyte reactivity after brain injury—: The role of galectins 1 and 3

Sirko

Irmler

Gascón

et al. 2015

Glia

109

View full text Add to dashboard Cite

show abstract

“…In the spinal cord, ependymal cells express the proliferation marker Ki-67 and act as stem cells after injury to produce astrocytes (27)(28)(29). Although previous evidence indicates that ependymal cells cannot act as stem cells in the forebrain (35-37), we nevertheless addressed the possibility that ependymal cells might be generating astrocytes in the neocortex of Fgfr LOF mutants after injury.…”

Section: Fgf Signaling Inhibits Astrocyte Activation After Traumatic mentioning

confidence: 95%

“…Moreover, severe ischemic injury immediately adjacent to the SVZ, but not superficial cortical injury, can induce the production of SVZ-derived astrocytes and their recruitment to the adjacent injury site (26). In the spinal cord, injury can induce ependymal cells to generate astrocytes (27)(28)(29). However, in the Fgfr LOF mutants, astrocytes become reactive throughout the cortex in the absence of detectable injury and in a time frame incompatible with astrocyte migration from the SVZ to all cortical areas.…”

Section: Significancementioning

confidence: 98%

Astrocyte activation is suppressed in both normal and injured brain by FGF signaling

Kang

Balordi

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

119

113

View full text Add to dashboard Cite

In the brain, astrocytes are multifunctional cells that react to insults and contain damage. However, excessive or sustained reactive astrocytes can be deleterious to functional recovery or contribute to chronic inflammation and neuronal dysfunction. Therefore, astrocyte activation in response to damage is likely to be tightly regulated. Although factors that activate astrocytes have been identified, whether factors also exist that maintain astrocytes as nonreactive or reestablish their nonreactive state after containing damage remains unclear. By using loss-and gainof-function genetic approaches, we show that, in the unperturbed adult neocortex, FGF signaling is required in astrocytes to maintain their nonreactive state. Similarly, after injury, FGF signaling delays the response of astrocytes and accelerates their deactivation. In addition, disrupting astrocytic FGF receptors results in reduced scar size without affecting neuronal survival. Overall, this study reveals that the activation of astrocytes in the normal and injured neocortex is not only regulated by proinflammatory factors, but also by factors such as FGFs that suppress activation, providing alternative therapeutic targets.brain damage | astrogliosis A strocytes are the most abundant cell type in the mammalian brain. The thin processes of protoplasmic astrocytes (graymatter astrocytes) canvas the neural parenchyma and make contact with several other cell types. Protoplasmic astrocytes carry out a variety of functions, including maintaining the bloodbrain barrier, ion homeostasis, neurotransmitter turnover, and synapse formation (1). Another major function of these astrocytes involves their activation in response to damage. Astrocyte activation, or astrogliosis, plays a central role in the response to most or all neurological insults including trauma, infections, stroke, tumorigenesis, neurodegeneration, and epilepsy. The extent of astrogliosis can influence long-term recovery, and the response of astrocytes to different insults is likely to be graded and complex (2, 3). Nevertheless, in most cases, astrocytes transiently become hypertrophic and express high levels of intermediate filaments such as GFAP, vimentin, tenascin C, and nestin, and, in cases of severe damage, astrocytes can also become proliferative and form a scar.Astrogliosis can have beneficial and detrimental effects on recovery. Astrogliosis is essential for minimizing the spread of damage and inflammation, but it is also inhibitory for axonal and cellular regeneration. For example, in transgenic mice in which reactive astrocytes are ablated or disabled, traumatic injury leads to the lack of normal scar formation, prolonged and more widespread inflammation, and a failure to reconstruct the bloodbrain barrier and maintain tissue integrity (4, 5). However, ablation or impairment of reactive astrocytes also leads to increased nerve fiber growth in the immediate vicinity of the injury site, which could improve axonal regeneration and functional recovery (4, 5). Therefore, levels of astrocy...

show abstract

“…Resident astrocytes form the peripheral part of the scar, while ependymal NSC-derived astrocytes constitute its central part (Barnabé-Heider et al, 2010). Moreover, while the former are implicated in restricting the infiltration of inflammatory cells (Okada et al, 2006;Herrmann et al, 2008) and in inhibiting the degranulation of neutrophils (Xie et al, 2010), the latter is required to reinforce the injured spinal cord (Sabelström et al, 2013).…”

Section: Bbb Damage and Reactive Gliosismentioning

confidence: 99%

The role of the immune system in central nervous system plasticity after acute injury

Peruzzotti-Jametti¹,

Donegá²,

Giusto³

et al. 2014

Neuroscience

View full text Add to dashboard Cite

Acute brain injuries cause rapid cell death that activates bidirectional crosstalks between the injured brain and the immune system.In the acute phase, the damaged central nervous system (CNS) activates resident and circulating immune cells via the local and systemic release of soluble mediators. This early immune activation is necessary to confine the injured tissue and foster the clearance of cellular debris, which would ultimately bring the inflammatory reaction to a close. In the chronic phase, a sustained immune activation is described in many CNS disorders, and the degree of this prolonged response has variable effects on the spontaneous brain regenerative processes. The challenge for treating acute CNS damages is to understand how to optimally engage and modify these immune responses, thus providing new strategies that will compensate for tissue lost to injury.Here we have reviewed the available information about the role and function of the innate and adaptive immune responses in influencing CNS plasticity during the acute and chronic phases of recovery after injury. We have examined how CNS damage evolves along the activation of main Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Europe PMC Funders Group

show abstract

Resident Neural Stem Cells Restrict Tissue Damage and Neuronal Loss After Spinal Cord Injury in Mice

Cited by 241 publications

References 27 publications

Astrocyte reactivity after brain injury—: The role of galectins 1 and 3

Astrocyte reactivity after brain injury—: The role of galectins 1 and 3

Astrocyte activation is suppressed in both normal and injured brain by FGF signaling

The role of the immune system in central nervous system plasticity after acute injury

Contact Info

Product

Resources

About