Alpha‐smooth muscle actin (α‐SMA) and nestin expression in reactive astrocytes in multiple sclerosis lesions: potential regulatory role of transforming growth factor‐beta 1 (TGF‐β1)

Moreels, Marjan; Vandenabeele, Frank; Dumont, Debora; Robben, Johan; Lambrichts, Ivo

doi:10.1111/j.1365-2990.2007.00910.x

Cited by 53 publications

(48 citation statements)

References 57 publications

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“…Scale bar 50 µm. (Color figure online) MS. Then, our observations are in agreement with the data related by Morrels et al [27]. Balo's concentric MS can lead to death but magnetic resonance imaging reveals that lesions can decrease in size and do not progress in some patients.…”

Section: Discussionsupporting

confidence: 95%

“…However, concerning pathological conditions affecting the CNS, one study reports the expression of α-SM actin by astrocytes in multiple sclerosis (MS) [27]. Indeed, Morrels et al [27] indicates that this subpopulation of astrocytes co-expressing GFAP and α-SM actin was observed in active or acute MS lesions. The authors did not find this astrocyte subpopulation in MS chronic inactive situations.…”

Section: Discussionmentioning

confidence: 97%

“…In the context of tissue repair, astrocytes and myofibroblasts share similarities [10]. For example, it has been shown that transforming growth factor-β1 which is known to induce myofibroblastic differentiation [28] also induces α-SM actin in cultured astrocytes [27]. In addition, it is known that transforming growth factor-β1 is secreted by macrophages [29] which participate in the important inflammation observed in active MS and particularly in Balo's concentric MS and which are numerous in close proximity with activated astrocytes.…”

Section: Discussionmentioning

confidence: 98%

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Isolation of Astrocytes Displaying Myofibroblast Properties and Present in Multiple Sclerosis Lesions

et al. 2017

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A wide heterogeneity of lesions can affect the central nervous system (CNS). In all situations where neurons are damaged, including multiple sclerosis (MS), a common reactive astrocytosis is present. Sedimentation field-flow fractionation (SdFFF) was used to sort astrocyte subpopulations. After SdFFF elution, cells, prepared from rat newborn cortex, were cultured and analyzed by immunocytofluorescence for glial fibrillary acidic protein (GFAP) and α-smooth muscle (SM) actin (a specific marker for myofibroblasts) expression. Cell contractile capacity was studied. Samples from patients with MS were also analyzed. Three main fractions (F1, F2, and F3) were isolated and compared with the total eluted population (TP). TP, F1, F2, and F3, contained respectively 74, 96, 12, and 98% of GFAP expressing astrocytes. In F3, astrocytes only expressed GFAP while in F1, astrocytes expressed both GFAP and α-SM actin. In F2 and TP, α-SM actin expression was barely detected. F3-derived cells showed higher contractile capacities compared with F1-derived cells. In one specific case of MS known as Baló's concentric MS, astrocytes expressing both GFAP and α-SM actin were detected. Using SdFFF, a population of astrocytes presenting myofibroblast properties was isolated. This subpopulation of astrocytes was also observed in a MS sample suggesting that it could be involved in lesion formation and remodeling during CNS pathologies.

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Section: Discussionsupporting

confidence: 95%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 98%

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Isolation of Astrocytes Displaying Myofibroblast Properties and Present in Multiple Sclerosis Lesions

et al. 2017

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“…We demonstrated that elongated, astrocytic processes after trauma played a crucial role in cell migration (Fig. 4 A-E), and intriguingly, similar elongated processes in reactive astrocytes are observed in multiple sclerosis (54). Because we observed neurites from transplanted cells in the cochlear nucleus, surface transplantation may be applied not only to neural systems in the superficial layers of the nervous system but also to those in deeper locations.…”

Section: Discussionmentioning

confidence: 76%

Cells transplanted onto the surface of the glial scar reveal hidden potential for functional neural regeneration

Sekiya

Holley

Hashido

et al. 2015

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

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Cell transplantation therapy has long been investigated as a therapeutic intervention for neurodegenerative disorders, including spinal cord injury, Parkinson’s disease, and amyotrophic lateral sclerosis. Indeed, patients have high hopes for a cell-based therapy. However, there are numerous practical challenges for clinical translation. One major problem is that only very low numbers of donor cells survive and achieve functional integration into the host. Glial scar tissue in chronic neurodegenerative disorders strongly inhibits regeneration, and this inhibition must be overcome to accomplish successful cell transplantation. Intraneural cell transplantation is considered to be the best way to deliver cells to the host. We questioned this view with experiments in vivo on a rat glial scar model of the auditory system. Our results show that intraneural transplantation to the auditory nerve, preceded by chondroitinase ABC (ChABC)-treatment, is ineffective. There is no functional recovery, and almost all transplanted cells die within a few weeks. However, when donor cells are placed on the surface of a ChABC-treated gliotic auditory nerve, they autonomously migrate into it and recapitulate glia- and neuron-guided cell migration modes to repair the auditory pathway and recover auditory function. Surface transplantation may thus pave the way for improved functional integration of donor cells into host tissue, providing a less invasive approach to rescue clinically important neural tracts.

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“…However, a significant upregulation of nestin is observed after cerebral injury suggesting that nestin is involved in brain repair (Frisen et al, 1995, Holmin et al, 1997, Douen et al, 2004). There is abundant evidence in the literature that after brain injury nestin expression in mature brains is a marker of reactive astrocytes (Clarke et al, 1994, Lin et al, 1995, Duggal et al, 1997, Holmin et al, 1997, Wei et al, 2002, Douen et al, 2004, Moreels et al, 2008). The lack of nestin expression, in our conditions, in the absence of DFP is shown in supplementary data.…”

Section: Discussionmentioning

confidence: 99%

4R-cembranoid protects against diisopropylfluorophosphate-mediated neurodegeneration

et al. 2014

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Many organophosphorous esters synthesized for applications in industry, agriculture, or warfare irreversibly inhibit acetylcholinesterase, and acute poisoning with these compounds causes life-threatening cholinergic overstimulation. Following classical emergency treatment with atropine, an oxime, and a benzodiazepine, surviving victims often suffer brain neurodegeneration. Currently, there is no pharmacological treatment to prevent this brain injury. Here we show that a cyclic diterpenoid, (1S,2E,4R,6R,7E,11E)-cembra-2,7,11-triene-4,6-diol (4R) ameliorates the damage caused by diisopropylfluorophosphate (DFP) in the hippocampal area CA1. DFP has been frequently used as a surrogate for the warfare nerve agent sarin. In rats, DFP is lethal at the dose used to cause brain damage. Therefore, to observe brain damage in survivors, the death rate was reduced by pre-administration of the peripherally acting antidotes pyridostigmine and methyl atropine or its analogue ipratropium. Pyridostigmine bromide, methyl atropine nitrate, and ipratropium bromide were dissolved in saline and injected intramuscularly at 0.1 mg/kg, 20 mg/kg, and 23 mg/kg, respectively. DFP (9 mg/kg) dissolved in cold water was injected intraperitoneally. 4R (6 mg/kg) dissolved in DMSO was injected subcutaneously, either 1 hour before or 5 or 24 hours after DFP. Neurodegeneration was assessed with Fluoro-Jade B and amino cupric silver staining; neuroinflammation was measured by the expression of nestin, a marker of activated astrocytes. Forty-eight hours after DFP administration, 4R decreased the number of dead neurons by half when injected before or after DFP. 4R also significantly decreased the number of activated astrocytes. These data suggest that 4R is a promising new drug that could change the therapeutic paradigm for acute poisoning with organophosphorous compounds by the implementation of a second-stage intervention after the classical countermeasure treatment.

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Alpha‐smooth muscle actin (α‐SMA) and nestin expression in reactive astrocytes in multiple sclerosis lesions: potential regulatory role of transforming growth factor‐beta 1 (TGF‐β1)

Cited by 53 publications

References 57 publications

Isolation of Astrocytes Displaying Myofibroblast Properties and Present in Multiple Sclerosis Lesions

Isolation of Astrocytes Displaying Myofibroblast Properties and Present in Multiple Sclerosis Lesions

Cells transplanted onto the surface of the glial scar reveal hidden potential for functional neural regeneration

4R-cembranoid protects against diisopropylfluorophosphate-mediated neurodegeneration

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