TREM2 and CD163 Ameliorate Microglia-Mediated Inflammatory Environment in the Aging Brain

Han, Xue; Liu, Yujia; Liu, Bin‐Wen; Ma, Zhengliang; Xia, Tianjiao; Gu, Xiaoping

doi:10.1007/s12031-022-01965-4

Cited by 9 publications

(3 citation statements)

References 49 publications

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“…This is confirmed by previous findings in other neuroinflammatory models (i.e., multiple sclerosis, Parkinson's disease, and sepsis) (Serrano-Martínez et al, 2024;Souza-Moreira et al, 2013;Wen et al, 2022), where cortistatin-modulated microglia markedly correlated with a better disease prognosis. Conversely, we observed a decreased expression of the scavenger receptor CD163, involved in the clearance of haemoglobin (Han et al, 2022). Interestingly, this factor is upregulated in patients with intracerebral haemorrhage and edema development (Roy-O'Reilly et al, 2017), suggesting a potential reduction of these events following cortistatin treatment.…”

Section: Discussionmentioning

confidence: 62%

Cortistatin exerts an immunomodulatory and neuroprotective role in a preclinical model of ischemic stroke

Castillo-González,

Buscemi,

Vargas-Rodríguez

et al. 2024

Preprint

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SummaryIschemic stroke is the result of a permanent or transient occlusion of a brain artery, leading to irreversible tissue injury and long-term sequelae. Despite ongoing improvements, therapeutic failure remains notorious, and stroke remains the second leading cause of death worldwide. Neuroinflammation, blood-brain barrier (BBB) breakdown, and immune deregulation are the major hallmarks of the pathogenesis and outcomes of brain ischemia. Understanding the interconnected and complex mechanisms and the endogenous mediators that globally modulate these responses is essential for developing successful therapeutic strategies. In this context, our study focuses on cortistatin, a neuropeptide widely distributed in the central nervous and immune systems. The anti-inflammatory, immunomodulatory, and neuroprotective properties of cortistatin make it an attractive novel therapeutic agent against ischemic stroke. To this aim, we evaluated the potential effect of cortistatin in the widely-known preclinical model of stroke MCAO (middle cerebral artery occlusion) in young (3 months old) and middle-aged (6 months old) wild-type mice. We observed that late treatment with cortistatin (24 h after stroke) improved neurological score, induced smaller lesions, reduced/modulated glial response, astrocytic scar formation and BBB recovery, and decreased peripheral immune activity. This beneficial effect of cortistatin suggests that multimodal-based therapies may represent a novel treatment for ischemic stroke, holding great promise compared to interventions targeting only a single aspect of stroke pathophysiology. Moreover, we found that the absence of cortistatin in young and middle-aged cortistatin-deficient animals increased susceptibility to stroke and worsened prognosis (i.e.,severe neurological score, altered microglial response, impaired astrocyte scar, disrupted BBB, dysregulated angiogenesis, and exacerbated immune infiltration and peripheral response). Interestingly, cortistatin treatment reversed stroke outcomes in animals lacking this neuropeptide, which highlights the key role of cortistatin in regulating the intricate interplay between the nervous and the immune systems, modulating dysregulated cellular and molecular responses from both systems that could impact brain homeostasis. Together, our findings underscore the relevance of identifying the endogenous and therapeutic role of neuro-immune mediators underlying ischemic stroke, and emphasize the critical need to consider multifactorial therapeutic approaches administered at later times and across different ages and phenotypes to extend the current therapeutic window for most patients who do not meet the clinical criteria.

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Section: Discussionmentioning

confidence: 62%

Cortistatin exerts an immunomodulatory and neuroprotective role in a preclinical model of ischemic stroke

Castillo-González,

Buscemi,

Vargas-Rodríguez

et al. 2024

Preprint

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“…As an emerging interdisciplinary subject, bioinformatics has been widely used in the field of life sciences. Recently, 10 Disease Markers the use of bioinformatics tools to study the genetic relationship between aging and inflammatory diseases, studies have found some correlation in molecular pathogenesis and disease development [46][47][48]. In this study, the four datasets identified 84 common DEGs, including 24 common upregulated genes and 5 common downregulated genes.…”

Section: Discussionmentioning

confidence: 92%

Identifying Common Genes and Pathways Associated with Periodontitis and Aging by Bioinformatics Analysis

Xie

Wang

et al. 2022

Disease Markers

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Background. This work used bioinformatic analysis to identify the relationship between periodontitis (PD) and aging, which could lead to new treatments for periodontal disease in the elderly. Method. Four microarray datasets were obtained from the Gene Expression Omnibus (GEO) database and analyzed in R language to identify differentially expressed genes (DEGs). The common DEGs of PD and aging were evaluated as key genes in this investigation by a Venn diagram. These common DEGs were analyzed through additional experiments and analysis, such as pathway analysis and enrichment analysis, and a network of protein-protein interactions (PPIs) was constructed. Cytoscape was used to visualize hub genes and critical modules based on the PPI network. Interaction of TF-genes and miRNAs with hub genes is identified. Result. 84 common DEGs were found between PD and aging. Cytohubba was performed on the PPI network obtained from STRING tool, and the top 10 genes (MMP2, PDGFRB, CTGF, CD34, CXCL12, VIM, IL2RG, ACTA2, COL4A2, and TAGLN) were selected as hub genes. VIM may be a potential biomarker in the analysis of linked hub gene regulatory networks, and hsa-mir-21 and hsa-mir-125b are predicted to be associated in PD and aging. Conclusion. This study investigated the key genes and pathways interactions between PD and aging, which may help reveal the correlation between PD and aging. The current research results are obtained by prediction, and follow-up biological experiments are required for further verification.

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“…Previous studies have highlighted CD45, CD68, and CD163 expressing cells as being frequently expressed in the pGBM TME (26,40). These markers are commonly expressed by TAMs and microglia (43,44). TAMs have been observed as a predominant cell population within the TME of pGBM (26,40).…”

Section: Characterization and Polarization Of Tumor-associated Macrop...mentioning

confidence: 96%

Myeloid cells as potential targets for immunotherapy in pediatric gliomas

Frederico,

Sharma,

Darling

et al. 2024

Front. Pediatr.

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Pediatric high-grade glioma (pHGG) including pediatric glioblastoma (pGBM) are highly aggressive pediatric central nervous system (CNS) malignancies. pGBM comprises approximately 3% of all pediatric CNS malignancies and has a 5-year survival rate of approximately 20%. Surgical resection and chemoradiation are often the standard of care for pGBM and pHGG, however, even with these interventions, survival for children diagnosed with pGBM and pHGG remains poor. Due to shortcomings associated with the standard of care, many efforts have been made to create novel immunotherapeutic approaches targeted to these malignancies. These efforts include the use of vaccines, cell-based therapies, and immune-checkpoint inhibitors. However, it is believed that in many pediatric glioma patients an immunosuppressive tumor microenvironment (TME) possess barriers that limit the efficacy of immune-based therapies. One of these barriers includes the presence of immunosuppressive myeloid cells. In this review we will discuss the various types of myeloid cells present in the glioma TME, including macrophages and microglia, myeloid-derived suppressor cells, and dendritic cells, as well as the specific mechanisms these cells can employ to enable immunosuppression. Finally, we will highlight therapeutic strategies targeted to these cells that are aimed at impeding myeloid-cell derived immunosuppression.

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TREM2 and CD163 Ameliorate Microglia-Mediated Inflammatory Environment in the Aging Brain

Cited by 9 publications

References 49 publications

Cortistatin exerts an immunomodulatory and neuroprotective role in a preclinical model of ischemic stroke

Cortistatin exerts an immunomodulatory and neuroprotective role in a preclinical model of ischemic stroke

Identifying Common Genes and Pathways Associated with Periodontitis and Aging by Bioinformatics Analysis

Myeloid cells as potential targets for immunotherapy in pediatric gliomas

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