Desmin expression profile in reactive astrocytes in the 3-nitropropionic acid–lesioned striatum of rat: Characterization and comparison with glial fibrillary acidic protein and nestin

Choi, Jun-Sub; Riew, Tae-Ryong; Kim, Hong Lim; Jin, Xuyan; Lee, Mun‐Yong

doi:10.1016/j.acthis.2017.10.003

Cited by 15 publications

(7 citation statements)

References 36 publications

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“…Consistent with our previous data ( Choi et al, 2017 ; Riew et al, 2017 ; Jin et al, 2018b ), approximately 70% of rats treated with 3-NP in our study developed characteristic neurological deficits including hindlimb impairment, recumbency, and impaired postural adjustments. In addition, all the animals examined in this study showed comparable expression patterns of GRP78 at each time point after 3-NP injection.…”

Section: Resultssupporting

confidence: 93%

Spatiotemporal Expression of GRP78 in the Blood Vessels of Rats Treated With 3-Nitropropionic Acid Correlates With Blood–Brain Barrier Disruption

Jin

Riew

Kim

et al. 2018

Front. Cell. Neurosci.

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Glucose-regulated protein (GRP78) or BiP, a 78-kDa chaperone protein located in the endoplasmic reticulum (ER), has recently been reported to be involved in the neuroglial response to ischemia-induced ER stress. The present study was designed to study the expression patterns of this protein and the cell types involved in the induction of GRP78 expression in rats treated with the mitochondrial toxin 3-nitropropionic acid (3-NP). GRP78 immunoreactivity was almost exclusively localized to striatal neurons in saline-treated controls, but GRP78 expression was induced in activated glial cells, including reactive astrocytes and activated microglia/macrophages, in the striata of rats treated with 3-NP. In the lesion core, increased GRP78 immunoreactivity was observed in the vasculature; this was evident in the lesion periphery of the core at 3 days after lesion induction, and was evenly distributed throughout the lesion core by 7 days after lesion induction. Vascular GRP78 expression was correlated, both temporally and spatially, with infiltration of activated microglia into the lesion core. In addition, this was coincident with the time and pattern of blood–brain barrier (BBB) leakage, detected by the extravasation of fluorescein isothiocyanate-albumin, an established BBB permeability marker. Vascular GRP78-positive cells in the lesion core were identified as endothelial cells, smooth muscle cells, and adventitial fibroblast-like cells, in which GRP78 protein was specifically localized to the cisternae of the rough ER and perinuclear cisternae, but not to other organelles such as mitochondria or nuclei. Thus, our data provide novel insights into the phenotypic and functional heterogeneity of GRP78-positive cells within the lesion core, suggesting the involvement of GRP78 in the activation/recruitment of activated microglia/macrophages and its potential role in BBB impairment in response to a 3-NP-mediated neurotoxic insult.

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Section: Resultssupporting

confidence: 93%

Spatiotemporal Expression of GRP78 in the Blood Vessels of Rats Treated With 3-Nitropropionic Acid Correlates With Blood–Brain Barrier Disruption

Jin

Riew

Kim

et al. 2018

Front. Cell. Neurosci.

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“…We next characterized PDGFR-β-positive cells in the lesion core by triple-labeling for PDGFR-β, RECA-1 and GFAP. At 3 days post-lesion, intense PDGFR-β expression was associated with most of the vasculature, including microvessels, in the lesion core, which was clearly demarcated by the absence of GFAP immunoreactivity, as described previously (Choi et al, 2017 ; Figures 3A,B,D,E ). In contrast, PDGFR-β immunoreactivity in the peri-lesional area, which was characterized by the presence of astrocytes with reactive phenotype, was observed only in a small fraction of the vasculature (Figures 3A–C ).…”

Section: Resultssupporting

confidence: 82%

PDGFR-β-Positive Perivascular Adventitial Cells Expressing Nestin Contribute to Fibrotic Scar Formation in the Striatum of 3-NP Intoxicated Rats

Riew

Choi

Kim

et al. 2018

Front. Mol. Neurosci.

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Perivascular cells expressing platelet-derived growth factor receptor beta (PDGFR-β) have recently been implicated in fibrotic scar formation after acute brain injury, but their precise identity and detailed morphological characteristics remain elusive. This study sought to characterize and define the cellular phenotype of vascular-associated cells expressing PDGFR-β in the striatum of rats treated with the mitochondrial toxin 3-nitropropionic acid (3-NP). In the control striatum, PDGFR-β-positive cells were invariably localized on the abluminal side of smooth muscle cells of larger caliber vessels, and demonstrated morphological features typical of perivascular fibroblasts. PDGFR-β expression increased and expanded to almost all vessels, including microvessels in the lesion core, at 7 days after 3-NP injection. The cells expressing PDGFR-β had ultrastructural features of fibroblasts undergoing active collagen synthesis: large euchromatic nuclei with a prominent nucleolus, well-developed rough endoplasmic reticulum (rER) with dilated cisterns and extracellular collagen fibrils. By 14 days, PDGFR-β-positive cells had somata located at a distance from the vasculature, and their highly ramified, slender processes overlapped with those from other cells, thus forming a plexus of processes in the extravascular space of the lesion core. In addition, their ultrastructural morphology and spatial correlation with activated microglia/macrophages were elaborated by three-dimensional reconstruction. Using a correlative light- and electron-microscopy technique, we found that the intermediate filament proteins nestin and vimentin were induced in PDGFRβ-positive fibroblasts in the lesion core. Collectively, our data suggest that perivascular PDGFR-β-positive fibroblasts are distinct from other vascular cell types, including pericytes and contribute to fibrotic scar formation in the lesion core after acute brain injury. Nestin and vimentin play critical roles in the structural dynamics of these reactive fibroblasts.

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“…Astrocytes become activated, proliferate and transform into fibrous elongated cells, which form an intertwined interface between injured and healthy tissue [9]. These are characterized by robust upregulation of glial fibrillary acidic protein (GFAP) [10–13]; its expression is also associated with transcription factors STAT-3 [9, 14], NF-κB [4], and JNK [15]. While it has been shown that the presence of activated astrocytes after SCI is vital for regeneration [16], a dense glial scar that forms after injury remains a barrier that hampers axonal growth across the lesion.…”

Section: Introductionmentioning

confidence: 99%

Transplantation of neural precursors generated from spinal progenitor cells reduces inflammation in spinal cord injury via NF-κB pathway inhibition

Karova

Wainwright

Urdzíková

et al. 2019

J Neuroinflammation

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BackgroundTraumatic spinal cord injury (SCI) triggers a chain of events that is accompanied by an inflammatory reaction leading to necrotic cell death at the core of the injury site, which is restricted by astrogliosis and apoptotic cell death in the surrounding areas. Activation of nuclear factor-κB (NF-κB) signaling pathway has been shown to be associated with inflammatory response induced by SCI. Here, we elucidate the pattern of activation of NF-κB in the pathology of SCI in rats and investigate the effect of transplantation of spinal neural precursors (SPC-01) on its activity and related astrogliosis.MethodsUsing a rat compression model of SCI, we transplanted SPC-01 cells or injected saline into the lesion 7 days after SCI induction. Paraffin-embedded sections were used to assess p65 NF-κB nuclear translocation at days 1, 3, 7, 10, 14, and 28 and to determine levels of glial scaring, white and gray matter preservation, and cavity size at day 28 after SCI. Additionally, levels of p65 phosphorylated at Serine536 were determined 10, 14, and 28 days after SCI as well as levels of locally secreted TNF-α.ResultsWe determined a bimodal activation pattern of canonical p65 NF-κB signaling pathway in the pathology of SCI with peaks at 3 and 28 days after injury induction. Transplantation of SCI-01 cells resulted in significant downregulation of TNF-α production at 10 and 14 days after SCI and in strong inhibition of p65 NF-κB activity at 28 days after SCI, mainly in the gray matter. Moreover, reduced formation of glial scar was found in SPC-01-transplanted rats along with enhanced gray matter preservation and reduced cavity size.ConclusionsThe results of this study demonstrate strong immunomodulatory properties of SPC-01 cells based on inhibition of a major signaling pathway. Canonical NF-κB pathway activation underlines much of the immune response after SCI including cytokine, chemokine, and apoptosis-related factor production as well as immune cell activation and infiltration. Reduced inflammation may have led to observed tissue sparing. Additionally, such immune response modulation could have impacted astrocyte activation resulting in a reduced glial scar.Electronic supplementary materialThe online version of this article (10.1186/s12974-019-1394-7) contains supplementary material, which is available to authorized users.

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Desmin expression profile in reactive astrocytes in the 3-nitropropionic acid–lesioned striatum of rat: Characterization and comparison with glial fibrillary acidic protein and nestin

Cited by 15 publications

References 36 publications

Spatiotemporal Expression of GRP78 in the Blood Vessels of Rats Treated With 3-Nitropropionic Acid Correlates With Blood–Brain Barrier Disruption

Spatiotemporal Expression of GRP78 in the Blood Vessels of Rats Treated With 3-Nitropropionic Acid Correlates With Blood–Brain Barrier Disruption

PDGFR-β-Positive Perivascular Adventitial Cells Expressing Nestin Contribute to Fibrotic Scar Formation in the Striatum of 3-NP Intoxicated Rats

Transplantation of neural precursors generated from spinal progenitor cells reduces inflammation in spinal cord injury via NF-κB pathway inhibition

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