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.

In vitro model for predicting the access and distribution of drugs in the brain using hCMEC/D3 cells

2021 ◽  
Author(s):  
Bárbara Sánchez-Dengra ◽  
Isabel González-Álvarez ◽  
Flavia Sousa ◽  
Marival Bermejo ◽  
Marta González-Álvarez ◽  
...  
Keyword(s):  
In Vitro Model ◽  
Vitro Model ◽  
The Brain

scholarly journals Delivery of Thyronamines (TAMs) to the Brain: A Preliminary Study

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1616
Author(s):  
Nicoletta di Leo ◽  
Stefania Moscato ◽  
Marco Borso' ◽  
Simona Sestito ◽  
Beatrice Polini ◽  
...  
Keyword(s):  
High Performance ◽  
In Vitro Model ◽  
New Drugs ◽  
Therapeutic Approaches ◽  
Neuroprotective Effects ◽  
Pharmacological Response ◽  
Preliminary Study ◽  
Vitro Model ◽  
The Brain

Recent reports highlighted the significant neuroprotective effects of thyronamines (TAMs), a class of endogenous thyroid hormone derivatives. In particular, 3-iodothyronamine (T1AM) has been shown to play a pleiotropic role in neurodegeneration by modulating energy metabolism and neurological functions in mice. However, the pharmacological response to T1AM might be influenced by tissue metabolism, which is known to convert T1AM into its catabolite 3-iodothyroacetic acid (TA1). Currently, several research groups are investigating the pharmacological effects of T1AM systemic administration in the search of novel therapeutic approaches for the treatment of interlinked pathologies, such as metabolic and neurodegenerative diseases (NDDs). A critical aspect in the development of new drugs for NDDs is to know their distribution in the brain, which is fundamentally related to their ability to cross the blood–brain barrier (BBB). To this end, in the present study we used the immortalized mouse brain endothelial cell line bEnd.3 to develop an in vitro model of BBB and evaluate T1AM and TA1 permeability. Both drugs, administered at 1 µM dose, were assayed by high-performance liquid chromatography coupled to mass spectrometry. Our results indicate that T1AM is able to efficiently cross the BBB, whereas TA1 is almost completely devoid of this property.

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.

TGN-020 alleviates edema and inhibits astrocyte activation and glial scar formation after spinal cord compression injury in rats

Life Sciences ◽  
2019 ◽  
Vol 222 ◽  
pp. 148-157 ◽  
Author(s):  
Jian Li ◽  
Zhiqiang Jia ◽  
Wen Xu ◽  
Weidong Guo ◽  
Mingchao Zhang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Compression ◽  
Cord Compression ◽  
Glial Scar ◽  
Scar Formation ◽  
Compression Injury ◽  
Astrocyte Activation

scholarly journals Methimazole Inhibits the Expression of GFAP and the Migration of Astrocyte in Scratched Wound Model In Vitro

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Lina Zhao ◽  
Xianyu Zhang ◽  
Chunhai Zhang
Keyword(s):  
Wound Healing ◽  
Time Window ◽  
Healing Process ◽  
Primary Cultures ◽  
Underlying Mechanism ◽  
Scar Formation ◽  
Activation Process ◽  
Cns Injury ◽  
Gfap Expression

Astrocytes respond to central nervous system (CNS) insults with varieties of changes, such as cellular hypertrophy, migration, proliferation, scar formation, and upregulation of glial fibrillary acidic protein (GFAP) expression. While scar formation plays a very important role in wound healing and prevents further bleeding by forming a physical barrier, it is also one of key features of CNS injury, resulting in glial scar formation (astrogliosis), which is closely related to treatment resistant epilepsy, chronic pain, and other devastating diseases. Therefore, slowing the astrocytic activation process may give a time window of axonal growth after the CNS injury. However, the underlying mechanism of astrocytic activation remains unclear, and there is no effective therapeutic strategy to attenuate the activation process. Here, we found that methimazole could effectively inhibit the GFAP expression in physiological and pathological conditions. Moreover, we scratched primary cultures of cerebral cortical astrocytes with and without methimazole pretreatment and investigated whether methimazole could slow the healing process in these cultures. We found that methimazole could inhibit the GFAP protein expression in scratched astrocytes and prolong the latency of wound healing in cultures. We also measured the phosphorylation of extracellular signal-regulated kinase (ERK) in these cultures and found that methimazole could significantly inhibit the scratch-induced GFAP upregulation. For the first time, our study demonstrated that methimazole might be a possible compound that could inhibit the astrocytic activation following CNS injury by reducing the ERK phosphorylation in astrocytes.

scholarly journals Photostimulation of Extravasation of Beta-Amyloid through the Model of Blood-Brain Barrier

Electronics ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1056
Author(s):  
Ekaterina Zinchenko ◽  
Maria Klimova ◽  
Aysel Mamedova ◽  
Ilana Agranovich ◽  
Inna Blokhina ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Beta Amyloid ◽  
Brain Barrier ◽  
Therapeutic Effects ◽  
Cervical Lymph Nodes ◽  
Blood Brain ◽  
The Central Nervous System ◽  
Vitro Model ◽  
The Brain

Alzheimer’s disease (AD) is an incurable pathology associated with progressive decline in memory and cognition. Phototherapy might be a new promising and alternative strategy for the effective treatment of AD, and has been actively discussed over two decades. However, the mechanisms of therapeutic photostimulation (PS) effects on subjects with AD remain poorly understood. The goal of this study was to determine the mechanisms of therapeutic PS effects in beta-amyloid (Aβ)-injected mice. The neurological severity score and the new object recognition tests demonstrate that PS 9 J/cm2 attenuates the memory and neurological deficit in mice with AD. The immunohistochemical assay revealed a decrease in the level of Aβ in the brain and an increase of Aβ in the deep cervical lymph nodes obtained from mice with AD after PS. Using the in vitro model of the blood-brain barrier (BBB), we show a PS-mediated decrease in transendothelial resistance and in the expression of tight junction proteins as well an increase in the BBB permeability to Aβ. These findings suggest that a PS-mediated BBB opening and the activation of the lymphatic clearance of Aβ from the brain might be a crucial mechanism underlying therapeutic effects of PS in mice with AD. These pioneering data open new strategies in the development of non-pharmacological methods for therapy of AD and contribute to a better understanding of the PS effects on the central nervous system.

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.

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