The effect of inflammatory cell-derived MCP-1 loss on neuronal survival during chronic neuroinflammation

Sawyer, Andrew J.; Tian, Weiming; Saucier-Sawyer, Jennifer K.; Rizk, Paul; Saltzman, W. Mark; Bellamkonda, Ravi V.; Kyriakides, Themis R.

doi:10.1016/j.biomaterials.2014.05.008

Cited by 54 publications

(40 citation statements)

References 68 publications

(77 reference statements)

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“…The impact that these chemokines have on the local environment has been shown through the use of genetic knockouts. The removal of monocyte chemoattractant protein 1 led to improved neuronal density [36] while caspase-1 knockout mice demonstrated significantly better recording quality as compared to wild type mice [37]. …”

Section: Introductionmentioning

confidence: 99%

Chronicin vivostability assessment of carbon fiber microelectrode arrays

et al. 2016

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Objective Individual carbon fiber microelectrodes can record unit activity in both acute and semi-chronic (∼1 month) implants. Additionally, new methods have been developed to insert a 16 channel array of carbon fiber microelectrodes. Before assessing the in vivo long-term viability of these arrays, accelerated soak tests were carried out to determine the most stable site coating material. Next, a multi-animal, multi-month, chronic implantation study was carried out with carbon fiber microelectrode arrays and silicon electrodes. Approach Carbon fibers were first functionalized with one of two different formulations of PEDOT and subjected to accelerated aging in a heated water bath. After determining the best PEDOT formula to use, carbon fiber arrays were chronically implanted in rat motor cortex. Some rodents were also implanted with a single silicon electrode, while others received both. At the end of the study a subset of animals were perfused and the brain tissue sliced. Tissue sections were stained for astrocytes, microglia, and neurons. The local reactive responses were assessed using qualitative and quantitative methods. Main results Electrophysiology recordings showed the carbon fibers detecting unit activity for at least 3 months with average amplitudes of ∼200 μV. Histology analysis showed the carbon fiber arrays with a minimal to non-existent glial scarring response with no adverse effects on neuronal density. Silicon electrodes showed large glial scarring that impacted neuronal counts. Significance This study has validated the use of carbon fiber microelectrode arrays as a chronic neural recording technology. These electrodes have demonstrated the ability to detect single units with high amplitude over 3 months, and show the potential to record for even longer periods. In addition, the minimal reactive response should hold stable indefinitely, as any response by the immune system may reach a steady state after 12 weeks.

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Section: Introductionmentioning

confidence: 99%

Chronicin vivostability assessment of carbon fiber microelectrode arrays

et al. 2016

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“…In the brain, CCL2 is mainly produced by macrophages and microglia, the key mediators of neuroinflammation [24]. During inflammatory progression, CCL2 not only attracts immune cells to specific sites but also promotes the release of other inflammatory factors, including IL-6 and IL-1β, exacerbating the extent of neuroinflammation [10,11].…”

Section: Discussionmentioning

confidence: 99%

Naringin provides neuroprotection in CCL2-induced cognition impairment by attenuating neuronal apoptosis in the hippocampus

et al. 2020

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Background: Chemokine CC motif ligand 2 (CCL2) is one of the most widely recognised proinflammatory chemokines in cognitive disorders. Currently, CCL2-targeting drugs are extremely limited. Thus, this study aimed to explore the neuroprotection afforded by naringin in CCL2-induced cognitive impairment in rats. Methods: Before the CCL2 intra-hippocampal injection, rats were treated with naringin for 3 consecutive days via intraperitoneal injection. Two days post-surgery, the Morris water maze (MWM) and novel object recognition (NORT) tests were performed to detect spatial learning and memory and object cognition, respectively. Nissl staining and dUTP nick-end labelling (TUNEL) staining were performed to assess histopathological changes in the hippocampus. Commercial kits were used to measure the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and the content of malondialdehyde (MDA). Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to examine the relative mRNA expression of interleukin 1β, (IL-1β), interleukin 6 (IL-6), glutamate/aspartate transporter (GLAST), glutamate transporter-1 (GLT-1), phosphate-activated glutaminase (PAG), cysteine aspartic acidspecific protease 8 (caspase-8), cysteine aspartic acid-specific protease 3 (caspase-3), cell lymphoma/leukaemia-2 (Bcl-2), and Bcl-2 associated X protein (Bax). Results: In the MWM, the average escape latency and average swimming distance were significantly reduced and the crossing times were increased in the naringin-treated groups, compared with the CCL2 group. The NORT results revealed that, compared with the CCL2 rats, the discrimination index in the naringin-treated rats increased significantly. Nissl and TUNEL staining revealed that naringin protected the structure and survival of the neurons in the CA1 zone of the hippocampus. In the naringin-treated groups, the SOD and GSH-Px activities were increased, whereas the MDA levels were decreased. Furthermore, in the naringin-treated groups, the relative mRNA expression of IL-1β and IL-6 was significantly decreased; GLAST and GLT-1 mRNA expression levels were increased, whereas PAG was decreased. In the naringin-treated groups, the relative mRNA expression levels of caspase-8, caspase-3, and Bax were decreased, whereas that of Bcl-2 was increased.

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“…By creating a chimeric mouse knockout model using previously described methods [16,17], we successfully disrupted the production of PDGF-B in myeloid lineage cells prior to implantation of a cell-free scaffold. Grafts taken from PGDF-KO mice demonstrate a larger total TEVG area, likely explained by a higher amount of remaining scaffold as well as a decreased neointimal area, and decreased ECM deposition after 2 weeks compared with WT controls.…”

Section: Discussionmentioning

confidence: 99%

The Role of Myeloid Cell-Derived PDGF-B in Neotissue Formation in a Tissue-Engineered Vascular Graft

et al. 2017

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Aim: Inflammatory myeloid lineage cells mediate neotissue formation in tissueengineered vascular grafts, but the molecular mechanism is not completely understood. We examined the role of vasculogenic PDGF-B in tissue-engineered vascular graft neotissue development. Materials & methods: Myeloid cell-specific PDGF-B knockout mice (PDGF-KO) were generated using bone marrow transplantation, and scaffolds were implanted as inferior vena cava interposition grafts in either PDGF-KO or wildtype mice. Results: After 2 weeks, grafts from PDGF-KO mice had more remaining scaffold polymer and less intimal neotissue development. Increased macrophage apoptosis, decreased smooth muscle cell proliferation and decreased collagen content was also observed. Conclusion: Myeloid cell-derived PDGF contributes to vascular neotissue formation by regulating macrophage apoptosis, smooth muscle cell proliferation and extracellular matrix deposition. Progress in tissue engineering continues to promise a solution to the lack of tissue available for reconstructive and replacement surgery. Our lab has worked over the past several years developing a tissue-engineered vascular graft (TEVG) for use in congenital heart and vascular surgery. Traditionally used prosthetic materials in the form of Dacron ® or Gore-Tex ® pose significant risk for thromboembolic and infectious complications and also lack growth capacity, making them less ideal for use in the pediatric population. Our ability to create a TEVG with growth capacity [1,2] has therefore been an important advancement in the field, but graft stenosis continues to be a major limitation to widespread clinical application. We have therefore concentrated our efforts on understanding the underlying processes of TEVG neotissue formation and stenosis development.We developed a murine model of TEVG stenosis [3] and found that seeding the grafts with bone marrow-derived mononuclear cells prior to implantation increases graft patency [4] in a dose responsive manner [5], but the seeded cells disappear shortly after implantation [6,7]. We thus hypothesized that a paracrine mechanism, rather than proliferation of seeded cells, was responsible for the remodeling of the TEVG and then demonstrated that host endothelial and smooth muscle cells from the adjacent vessel migrate to form the TEVG neotissue.Host monocytes and macrophages were identified as key mediators of graft remodeling. They infiltrate the graft in large numbers shortly after implantation, and excessive infiltration leads to graft stenosis [8].

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The effect of inflammatory cell-derived MCP-1 loss on neuronal survival during chronic neuroinflammation

Cited by 54 publications

References 68 publications

Chronicin vivostability assessment of carbon fiber microelectrode arrays

Chronicin vivostability assessment of carbon fiber microelectrode arrays

Naringin provides neuroprotection in CCL2-induced cognition impairment by attenuating neuronal apoptosis in the hippocampus

The Role of Myeloid Cell-Derived PDGF-B in Neotissue Formation in a Tissue-Engineered Vascular Graft

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