scholarly journals Analysis of the Neurotropic and Anti-inflammatory Effects of Neuroelectrode Functionalization with a Heparan Sulphate Mimetic

2021 ◽  
Author(s):  
Catalina Vallejo Giraldo ◽  
Ouidir Ouidja Mohand ◽  
Minh Bao Huynh ◽  
Alexandre Trotier ◽  
Katarzyna Krukiewicz ◽  
...  
Keyword(s):  
Cell Response ◽  
Potential Role ◽  
Heparan Sulphate ◽  
Glial Scar ◽  
Scar Formation ◽  
Neural Interface ◽  
Host Cell Response ◽  
Neural Tissues ◽  
First Time

Further in the search for biomimicry of the properties analogous to neural tissues, and with an ultimate goal of mitigating electrode deterioration via reactive host cell response and glial scar formation, the bio-functionalisation of PEDOT:PTS neural coating is here presented using a heparan mimetic termed (HM) F6. A sulphated mimetic polyanion, with a potential role in neuromodulation in neurodegenerative diseases, and used here for the first time as neural coating. This work acts as a first step towards the use of HM biological dopants, to enhance neuroelectrode functionality, to promote neural outgrowth and to maintain minimal glial scar formation in vitro at the neural-interface. Further, this study opens new possibilities for the evaluation of glycan mimetics in neuroelectrode functionalisation.

Abstract WMP38: Inhibition of Rip1 Kinase Improves Brain Functional Recovery After Ischemic Stroke via Reducing Astrocytic Scar Formation

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Huiling Zhang ◽  
Zhong-Sheng Li ◽  
Yong Ni ◽  
Xian-Yong Zhou ◽  
Shi-Gang Qiao
Keyword(s):  
Ischemic Stroke ◽  
Western Blotting ◽  
Functional Recovery ◽  
Recovery Phase ◽  
Glial Scar ◽  
Scar Formation ◽  
Western Blotting Analysis ◽  
Protein Levels

During the recovery phase of ischemic stroke, one of the major barriers for the spontaneous neuronal axon regeneration is the formation of astrogliosis and glial scar, and targeting astrogliosis becomes a therapeutic strategy for ischemic stroke. However, the mechanism regulating the process of scar components after ischemia still remains poorly understood. The aim of this study was to observe the role of RIP1 kinase (RIP1K), the key regulator of necroptosis (programmed necrosis) in the brain functional recovery after ischemic stroke and in the ischemic stroke-induced astrogliosis and glial scar formation in both in vitro and in vivo glial scar models. The glial scar formation model in vitro or in vivo was established by using primary cultured astrocyte subjected to 6 hours of oxygen-glucose deprivation (OGD) following 12 hours or 24 hours reperfusion, or by 90 min of transient middle cerebral artery occlusion (tMCAO) and reperfusion in rats. Western blotting analysis and immunohistochemical assay showed that knockdown of RIP1K by lentivirally-delivered shRNAs against RIP1K (shRNA RIP1K) could decrease several protein levels of glial scar markers such as glial fibillary acidic protein (GFAP), neurocan and phosphacan both in in vitro and in vivo glial scar models. Furthermore, western blotting analysis showed that knockdown of RIP1K reduced the protein levels of VEGF-D receptor 3 in in vitro glial scar models. In addition, knockdown of RIP1K also notably reduced the shrinking volume and ameliorated the behavioral symptoms in the recovery phase of rats after tMCAO. And immunocytochemistry assay demonstrated that RIP1K knockdown promoted the neuronal axonal generation in a neuron and astrocyte co-culture system. Our data indicates that RIP1K might play an important role in the formation of glial scar after ischemic stroke via promoting the function of VEGF-D receptor 3 in astrocytes.

scholarly journals Different Functions of Recombinantly Expressed Domains of Tenascin-C in Glial Scar Formation

2021 ◽  
Vol 11 ◽  
Author(s):  
Dunja Bijelić ◽  
Marija Adžić ◽  
Mina Perić ◽  
Igor Jakovčevski ◽  
Eckart Förster ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Proliferation ◽  
Glial Scar ◽  
Scar Formation ◽  
Injury Site ◽  
Tenascin C ◽  
Gap Closure ◽  
Cord Injury ◽  
Alternatively Spliced

Extracellular matrix glycoprotein tenascin-C (TnC) is highly expressed in vertebrates during embryonic development and thereafter transiently in tissue niches undergoing extensive remodeling during regeneration after injury. TnC’s different functions can be attributed to its multimodular structure represented by distinct domains and alternatively spliced isoforms. Upon central nervous system injury, TnC is upregulated and secreted into the extracellular matrix mainly by astrocytes. The goal of the present study was to elucidate the role of different TnC domains in events that take place after spinal cord injury (SCI). Astrocyte cultures prepared from TnC-deficient (TnC-/-) and wild-type (TnC+/+) mice were scratched and treated with different recombinantly generated TnC fragments. Gap closure, cell proliferation and expression of GFAP and cytokines were determined in these cultures. Gap closure in vitro was found to be delayed by TnC fragments, an effect mainly mediated by decreasing proliferation of astrocytes. The most potent effects were observed with fragments FnD, FnA and their combination. TnC-/- astrocyte cultures exhibited higher GFAP protein and mRNA expression levels, regardless of the type of fragment used for treatment. Application of TnC fragments induced also pro-inflammatory cytokine production by astrocytes in vitro. In vivo, however, the addition of FnD or Fn(D+A) led to a difference between the two genotypes, with higher levels of GFAP expression in TnC+/+ mice. FnD treatment of injured TnC-/- mice increased the density of activated microglia/macrophages in the injury region, while overall cell proliferation in the injury site was not affected. We suggest that altogether these results may explain how the reaction of astrocytes is delayed while their localization is restricted to the border of the injury site to allow microglia/macrophages to form a lesion core during the first stages of glial scar formation, as mediated by TnC and, in particular, the alternatively spliced FnD domain.

scholarly journals CD36 is Involved in Astrocyte Activation and Astroglial Scar Formation

2012 ◽  
Vol 32 (8) ◽  
pp. 1567-1577 ◽  
Author(s):  
Yi Bao ◽  
Luye Qin ◽  
Eunhee Kim ◽  
Sangram Bhosle ◽  
Hengchang Guo ◽  
...  
Keyword(s):  
Glial Scar ◽  
Scar Formation ◽  
Astrocyte Activation ◽  
Gfap Expression ◽  
Potential Strategy ◽  
Vitro Model ◽  
Delayed Closure ◽  
Interfering Rna ◽  
The Brain

Inflammation is an essential component for glial scar formation. However, the upstream mediator(s) that triggers the process has not been identified. Previously, we showed that the expression of CD36, an inflammatory mediator, occurs in a subset of astcotyes in the peri-infarct area where the glial scar forms. This study investigates a role for CD36 in astrocyte activation and glial scar formation in stroke. We observed that the expression of CD36 and glial fibrillary acidic protein (GFAP) coincided in control and injured astrocytes and in the brain. Furthermore, GFAP expression was attenuated in CD36 small interfering RNA transfected astrocytes or in the brain of CD36 knockout (KO) mice, suggesting its involvement in GFAP expression. Using an in-vitro model of wound healing, we found that CD36 deficiency attenuated the proliferation of astrocytes and delayed closure of the wound gap. Furthermore, stroke-induced GFAP expression and scar formation were significantly attenuated in the CD36 KO mice compared with wild type. These findings identify CD36 as a novel mediator for injury-induced astrogliosis and scar formation. Targeting CD36 may serve as a potential strategy to reduce glial scar formation in stroke.

scholarly journals Control protocol for robust in vitro glial scar formation around microwires: Essential roles of bFGF and serum in gliosis

2009 ◽  
Vol 181 (2) ◽  
pp. 170-177 ◽  
Author(s):  
Vadim S. Polikov ◽  
Eric C. Su ◽  
Matthew A. Ball ◽  
Jau-Shyong Hong ◽  
William M. Reichert
Keyword(s):  
Glial Scar ◽  
Scar Formation ◽  
Control Protocol

Curcumin inhibits glial scar formation by suppressing astrocyte-induced inflammation and fibrosis in vitro and in vivo

2017 ◽  
Vol 1655 ◽  
pp. 90-103 ◽  
Author(s):  
Jichao Yuan ◽  
Wei Liu ◽  
Haitao Zhu ◽  
Yaxing Chen ◽  
Xuan Zhang ◽  
...  
Keyword(s):  
Glial Scar ◽  
Scar Formation

scholarly journals Regulation of RhoA by STAT3 coordinates glial scar formation

2017 ◽  
Vol 216 (8) ◽  
pp. 2533-2550 ◽  
Author(s):  
Francois Renault-Mihara ◽  
Masahiko Mukaino ◽  
Munehisa Shinozaki ◽  
Hiromi Kumamaru ◽  
Satoshi Kawase ◽  
...  
Keyword(s):  
Intracellular Signaling ◽  
Glial Scar ◽  
Scar Formation ◽  
Small Gtpase ◽  
Reactive Astrocytes ◽  
Signaling Mechanisms ◽  
And Migration ◽  
Phosphatase And Tensin Homologue ◽  
Transcription 3

Understanding how the transcription factor signal transducer and activator of transcription–3 (STAT3) controls glial scar formation may have important clinical implications. We show that astrocytic STAT3 is associated with greater amounts of secreted MMP2, a crucial protease in scar formation. Moreover, we report that STAT3 inhibits the small GTPase RhoA and thereby controls actomyosin tonus, adhesion turnover, and migration of reactive astrocytes, as well as corralling of leukocytes in vitro. The inhibition of RhoA by STAT3 involves ezrin, the phosphorylation of which is reduced in STAT3-CKO astrocytes. Reduction of phosphatase and tensin homologue (PTEN) levels in STAT3-CKO rescues reactive astrocytes dynamics in vitro. By specific targeting of lesion-proximal, reactive astrocytes in Nestin-Cre mice, we show that reduction of PTEN rescues glial scar formation in Nestin-Stat3+/− mice. These findings reveal novel intracellular signaling mechanisms underlying the contribution of reactive astrocyte dynamics to glial scar formation.

TGF-β Secretion by M2 Macrophages Induces Glial Scar Formation by Activating Astrocytes In Vitro

2019 ◽  
Vol 69 (2) ◽  
pp. 324-332 ◽  
Author(s):  
Gongyu Song ◽  
Rui Yang ◽  
Qian Zhang ◽  
Long Chen ◽  
Dujuan Huang ◽  
...  
Keyword(s):  
Glial Scar ◽  
Scar Formation ◽  
M2 Macrophages

scholarly journals Potential IFNγ Modulation of Inflammasome Pathway in Chlamydia trachomatis Infected Synovial Cells

Life ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1359
Author(s):  
Simone Filardo ◽  
Marisa Di Pietro ◽  
Federica Frasca ◽  
Fabiana Diaco ◽  
Mirko Scordio ◽  
...  
Keyword(s):  
Chlamydia Trachomatis ◽  
Synovial Cells ◽  
Chlamydia Trachomatis Infection ◽  
Host Cell Response ◽  
Caspase 1 ◽  
Ifn Γ ◽  
Subsequent Activation ◽  
Vitro Model ◽  
First Time

Following a Chlamydia trachomatis infection, the host immune response is characterized by its recognition via Toll-like and Nod-like Receptors, and the subsequent activation of interferon (IFN)-γ-mediated signaling pathways. Recently, the inflammasome-mediated host cell response has emerged to play a role in the physiopathology of C. trachomatis infection. Here we investigated, for the first time, the interaction of IFN-γ and inflammasome in an in vitro model of C. trachomatis-infected primary human synovial cells. Chlamydial replication as well as the expression of caspase-1, IL-1β, as well as IL-18 and IL-6, were assayed. Our results demonstrated the inhibitory activity of IFN-γ by interfering with the inflammasome network through the downregulation of caspase-1 mRNA expression. In addition, the ability of C. trachomatis to hinder the inflammasome pathway favoring its intracellular survival within synovial cells, was observed. Overall, our data suggest a potential mechanism of immune evasion by C. trachomatis in synovial cells, that may be contested by IFN-γ.

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