Fate mapping of peripherally derived macrophages reveals a long-lasting engrafted population that maintains a distinct transcriptomic profile for up to 8 months after Traumatic Brain Injury DOI Open Access
Maria Serena Paladini, Benjamin A. Yang, Xi Feng

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 20, 2024

Abstract Traumatic Brain Injury (TBI) is one of the most established environmental risk factors for development dementia and long term neurological deficits representing a critical health problem our society. It well-established that TBI-induced neuroinflammation contributes to long-lasting cognitive engages brain-resident macrophages (microglia) as well monocytes-derived (MDMs) recruited from periphery. While numerous studies have characterized microglia response TBI, role early infiltrated MDMs in dysfunctions, fate TBI remains unknown. Microglia distinct embryological origins it unclear if can fully transition after infiltrating brain. This gap knowledge due fact brain engraftment, stop expressing their signature markers, thus making discrimination resident cells elusive. Here, first time, we longitudinally trace by taking advantage two complementary yet mapping mouse lines, CCR2-creER T2 Ms4a3-cre, where inflammatory monocytes are permanently labeled even situ reprogramming. We demonstrated persist up 8 months adult female male mice. Notably, retain phagocytic activity while remaining transcriptomically microglia, show associated with aging disease. Our data significantly advance understanding provide developing more targeted therapeutic interventions myeloid cells.

Language: Английский

Microglial depletion and repopulation differentially modulate sleep and inflammation in a mouse model of traumatic brain injury DOI Creative Commons
Katherine R. Giordano,

Tabitha R.F. Green,

Mark R. Opp

et al.

Neurobiology of Sleep and Circadian Rhythms, Journal Year: 2025, Volume and Issue: unknown, P. 100115 - 100115

Published: Feb. 1, 2025

Language: Английский

Citations

0
Cortical reactive microglia activate astrocytes, increasing neurodegeneration in human alcohol use disorder DOI Creative Commons
Fulton T. Crews, Liya Qin, Leon G. Coleman

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 29, 2025

Abstract Reactive microglia are associated with multiple brain diseases that may have specific disease phenotypes. Studies of human cortical in alcohol use disorder (AUD) characterized reactive microglial subtypes by transcriptome or histology. Preclinical studies found proinflammatory signaling and contribute to increases drinking preference, behaviors unique AUD. This study post-mortem AUD combines immunoreactivity (+IR) protein changes gene expression (mRNA) orbital frontal cortex (OFC) an effort better characterize the Since linked astrocytes (GFAP+IR), oxidative DNA damage (8-hydroxy-2′-deoxyguanosine (8-OHdG+IR), neurodegeneration (NeuN, MAP2+IR), we assessed these markers within OFC. were identified Iba1, CD11b (Mac1-OX42), CX3CR1, CSF1R, CD68, CCR2, P2RY12, SYK, TFE3+IR OFC compared control moderate drinkers. Tmem119+IR was decreased brain. Several genes had parallel +IR mRNA. However, several commonly used identify did not show mRNA, including CSF1R+IR. Overall, monocyte phagocytic markers, but TREM2, DAP, complement genes. highly correlated astrocyte GFAP+IR, stress 8-OHdG+IR, loss neurons MAP2+IR). Mediation analysis indicated both stress, only significantly (NeuN+IR). These findings supported mouse finding chronic ethanol exposure is inhibited DREADD blockade activation. Our support a distinct phenotype activates astrocytes, contributing possibly heavy drinking.

Language: Английский

Citations

0
Diffuse traumatic brain injury induced stimulator of interferons (STING) signaling in microglia drives cortical neuroinflammation, neuronal dysfunction, and impaired cognition DOI Creative Commons
Jonathan M. Packer,

Samantha G. Giammo,

Lynde M. Wangler

et al.

Journal of Neuroinflammation, Journal Year: 2025, Volume and Issue: 22(1)

Published: April 30, 2025

Language: Английский

Citations

0
Astrocyte-mediated inflammatory responses in traumatic brain injury: mechanisms and potential interventions DOI Creative Commons
Haifeng Zhang, Xian Zhang, Yan Chai

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: May 8, 2025

Astrocytes play a pivotal role in the inflammatory response triggered by traumatic brain injury (TBI). They are not only involved initial following but also significantly contribute to Astrocyte activation and inflammasome release key processes pathophysiology of TBI, affecting progression secondary long-term outcomes. This comprehensive review explores complex triggering mechanisms astrocyte intricate pathways controlling inflammasomes from activated astrocytes, subsequent neuroinflammatory cascade its multifaceted roles after injury. The exploration these deepens our understanding highlights potential astrocytes as critical therapeutic targets for TBI interventions. We then evaluate cutting-edge research aimed at targeted approaches modulate pro-inflammatory discuss emerging pharmacological interventions their efficacy preclinical models. Given that there has yet be relevant elucidating specific intracellular targeting substances, this aims provide nuanced astrocyte-mediated neuroinflammation elucidate promising avenues could fundamentally change management improve patient development neurological sequelae. By releasing variety cytokines chemokines, regulate neuroinflammation, thereby influencing survival function surrounding cells. In recent years, researchers have concentrated efforts on signaling crosstalk between other cells under various conditions, while exploring paper which produce mediators during acute phase post-TBI, including signaling, blood-brain barrier integrity, neuronal protection. Additionally, we current clinical intervention strategies mitigate damage enhance recovery TBI. Finally, explore feasibility pharmacologically assessing activity post-TBI biomarker predicting acute-phase changes.

Language: Английский

Citations

0
20-Hydroxyeicosatetraenoic Acid Regulates the Src/EGFR/NF-κB Signaling Pathway Via GPR75 to Activate Microglia and Promote TBI in the Immature Brain DOI

Zhihui Ma,

Ya‐Lei Ning,

Xiaoli Chen

et al.

Neurochemical Research, Journal Year: 2024, Volume and Issue: 50(1)

Published: Nov. 14, 2024

Language: Английский

Citations

2
Neurotropic murine coronavirus mediated demyelination: Factors dampening pathogenesis DOI
Mi‐Hyun Hwang, Cornelia C. Bergmann

Journal of Neuroimmunology, Journal Year: 2024, Volume and Issue: 393, P. 578382 - 578382

Published: June 1, 2024

Language: Английский

Citations

1
Identification of key genes and enriched biological processes in diabetes-associated traumatic brain injury through weighted gene correlation network and bioinformatics analysis DOI Creative Commons
Umar Faruk Saidu, Ibrahim Bulama

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 14, 2024

Abstract Traumatic brain injury (TBI) is a significant cause of morbidity and mortality worldwide, with long-term neurological psychological impacts. Recent studies have indicated that diabetes (T1DM) exacerbates the outcomes TBI, leading to more severe cognitive deficits increased risk complications. This study investigated underlying molecular mechanisms potential therapeutic targets for T1DM-associated TBI. Four mRNA datasets (GSE4745, GSE125451, GSE173975, GSE80174) downloaded from GEO repository were used in this study. Using limma, total 284 differentially expressed genes (DEGs) identified T1DM, which 11 upregulated 9 downregulated. GSEA showed these DEGs significantly enriched cell communication, lipid metabolic process, PPAR signaling. A 584 186 mainly immune response-regulating signaling pathway. WGCNA 122 TIDM-related modules 368 TBI-related module. GO KEGG enrichment analysis T1DM module correlated process ribosome biogenesis, while TBI inflammation response, including leukocyte mediated immunity, lymphocyte cytokine receptor activity. PPI network 20 hub genes, 14 ribosomal genes: Rpl23, Rps3a, Rps6, Rpl5, Rpl17, Rps24, Rpl23a, Rps4x, Rpl9, Rps15a14, Rpl30, Rpl31, Rps25, Rps27a-2. The primarily related biogenesis RNA post-transcriptional regulation. Ptprc, Tp53, Stat1, Stat3, Tyrobp, Itgad, Csf1r, Itgb2, Rac2, Icam1, Myd88, Cd44, Vav1, Aif1, C1qa, Laptm5, B2m, Fcer1g, Lyn. inflammatory mediators response. Based on overlap Cmklr1, Mgst1, Plin2, as key Functional they cellular response hydroperoxide, cytokine-mediated activity, regulation sequestering triglyceride, negative IL-12 production, positive macrophage chemotaxis. Reactome, Plin2 neutrophil degranulation, storage, respectively. We concluded Lipid droplet dysregulation Neuroinflammation are positively may be important biomarkers treatment diabetic

Language: Английский

Citations

0
Fate mapping of peripherally derived macrophages reveals a long-lasting engrafted population that maintains a distinct transcriptomic profile for up to 8 months after Traumatic Brain Injury DOI Open Access
Maria Serena Paladini, Benjamin A. Yang, Xi Feng

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 20, 2024

Abstract Traumatic Brain Injury (TBI) is one of the most established environmental risk factors for development dementia and long term neurological deficits representing a critical health problem our society. It well-established that TBI-induced neuroinflammation contributes to long-lasting cognitive engages brain-resident macrophages (microglia) as well monocytes-derived (MDMs) recruited from periphery. While numerous studies have characterized microglia response TBI, role early infiltrated MDMs in dysfunctions, fate TBI remains unknown. Microglia distinct embryological origins it unclear if can fully transition after infiltrating brain. This gap knowledge due fact brain engraftment, stop expressing their signature markers, thus making discrimination resident cells elusive. Here, first time, we longitudinally trace by taking advantage two complementary yet mapping mouse lines, CCR2-creER T2 Ms4a3-cre, where inflammatory monocytes are permanently labeled even situ reprogramming. We demonstrated persist up 8 months adult female male mice. Notably, retain phagocytic activity while remaining transcriptomically microglia, show associated with aging disease. Our data significantly advance understanding provide developing more targeted therapeutic interventions myeloid cells.

Language: Английский

Citations

0