Microglia preserve visual function in the aging retina by supporting retinal pigment epithelial health DOI Creative Commons

Margarete M. Karg,

May Moorefield,

Emma Hoffmann

et al.

Immunity & Ageing, Journal Year: 2023, Volume and Issue: 20(1)

Published: Oct. 14, 2023

Abstract Background Increased age is a risk factor for the development and progression of retinal diseases including age-related macular degeneration (AMD). Understanding changes that occur in eye due to aging important enhancing our understanding AMD pathogenesis novel therapies. Microglia, resident brain immune cells are associated with both maintaining homeostasis protection neurons loss microglia could be significant player related neurodegeneration. One characteristic migration from inner outer retina where they reside subretinal space (SRS) contact pigment epithelial (RPE) cells. The role aged unknown. Here, we depleted C57/BL6 mice fed 6 weeks chow containing PLX5622, small molecule inhibitor colony-stimulating factor-1 receptor (Csf1r) required microglial survival. Results P2RY12 + displayed highly amoeboid activated morphology were filled autofluorescence droplets reminiscent lipofuscin. TEM indicates actively phagocytize shed photoreceptor segments, one main functions pigmented PLX5622 treatment up 90% was visual function. Mice on depletion diet showed reduced contrast sensitivity significantly lower electroretinogram c-wave, measurement RPE functionality, compared age-matched controls. c-wave coincided increased swelling absence microglia. Conclusions We conclude preserve function support cell function, by phagocytosing segments lipids, therefore compensating known decline phagocytosis.

Language: Английский

Dysregulated brain-gut axis in the setting of traumatic brain injury: review of mechanisms and anti-inflammatory pharmacotherapies DOI Creative Commons

Mahmoud G. El Baassiri,

Zachariah Raouf,

Sarah Badin

et al.

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: May 10, 2024

Abstract Traumatic brain injury (TBI) is a chronic and debilitating disease, associated with high risk of psychiatric neurodegenerative diseases. Despite significant advancements in improving outcomes, the lack effective treatments underscore urgent need for innovative therapeutic strategies. The brain-gut axis has emerged as crucial bidirectional pathway connecting gastrointestinal (GI) system through an intricate network neuronal, hormonal, immunological pathways. Four main pathways are primarily implicated this crosstalk, including systemic immune system, autonomic enteric nervous systems, neuroendocrine microbiome. TBI induces profound changes gut, initiating unrestrained vicious cycle that exacerbates axis. Alterations gut include mucosal damage malabsorption nutrients/electrolytes, disintegration intestinal barrier, increased infiltration cells, dysmotility, dysbiosis, enteroendocrine cell (EEC) dysfunction disruption (ENS) (ANS). Collectively, these further contribute to neuroinflammation neurodegeneration via gut-brain In review article, we elucidate roles various anti-inflammatory pharmacotherapies capable attenuating dysregulated inflammatory response along TBI. These agents hormones such serotonin, ghrelin, progesterone, ANS regulators beta-blockers, lipid-lowering drugs like statins, flora modulators probiotics antibiotics. They attenuate by targeting distinct both post-TBI. exhibit promising potential mitigating inflammation enhancing neurocognitive outcomes patients.

Language: Английский

Citations

12
The ageing central nervous system in multiple sclerosis: the imaging perspective DOI Creative Commons
Massimo Filippi, Paolo Preziosa, Frederik Barkhof

et al.

Brain, Journal Year: 2024, Volume and Issue: 147(11), P. 3665 - 3680

Published: July 22, 2024

Abstract The interaction between ageing and multiple sclerosis is complex carries significant implications for patient care. Managing effectively requires an understanding of how impact brain structure function. Ageing inherently induces changes, including reduced plasticity, diminished grey matter volume, ischaemic lesion accumulation. When combined with pathology, these age-related alterations may worsen clinical disability. also influence the response patients to therapies and/or their side effects, highlighting importance adjusted treatment considerations. MRI highly sensitive age- sclerosis-related processes. Accordingly, can provide insights into relationship sclerosis, enabling a better pathophysiological interplay informing selection. This review summarizes current knowledge on immunopathological aspects in CNS context sclerosis. Starting from immunosenescence, ageing-related pathological mechanisms specific features like enlarged Virchow-Robin spaces, this then explores aspects, late-onset age diagnostic criteria, comorbidity effects imaging features. role neurodegeneration, iron dynamics myelin changes influenced by contribute defining patients, are discussed.

Language: Английский

Citations

9
Microglial activation and polarization in type 2 diabetes-related cognitive impairment: A focused review of pathogenesis DOI Creative Commons

Yue Tian,

Guangchan Jing,

Mei Ma

et al.

Neuroscience & Biobehavioral Reviews, Journal Year: 2024, Volume and Issue: 165, P. 105848 - 105848

Published: Aug. 13, 2024

Microglia, as immune cells in the central nervous system, are closely related to cognitive impairment associated with type 2 diabetes (T2D). Preliminary explorations have investigated relationship between T2D-related and activation polarization of microglia. This review summarizes potential mechanisms microglial context T2D. It discusses inflammatory responses, neuronal apoptosis, amyloid-β deposition, abnormal phosphorylation Tau protein mediated by polarization, exploring connections from multiple perspectives. Additionally, this provides references for future treatment targeting microglia clinical translation.

Language: Английский

Citations

9
Microglia moonlighting after traumatic brain injury: aging and interferons influence chronic microglia reactivity DOI Open Access
Lynde M. Wangler, Jonathan P. Godbout

Trends in Neurosciences, Journal Year: 2023, Volume and Issue: 46(11), P. 926 - 940

Published: Sept. 16, 2023

Language: Английский

Citations

17
Deplete and repeat: microglial CSF1R inhibition and traumatic brain injury DOI Creative Commons

Rebecca Boland,

Olga N. Kokiko‐Cochran

Frontiers in Cellular Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Feb. 21, 2024

Traumatic brain injury (TBI) is a public health burden affecting millions of people. Sustained neuroinflammation after TBI often associated with poor outcome. As result, increased attention has been placed on the role immune cells in post-injury recovery. Microglia are highly dynamic and play key neuroinflammatory response. Therefore, microglia represent malleable target that could substantially influence long-term outcome TBI. This review highlights cell specific pathophysiology. have manipulated via genetic deletion, drug inhibition, pharmacological depletion various pre-clinical models. Notably, colony stimulating factor 1 (CSF1) its receptor (CSF1R) gained much traction recent years as microglia. CSF1R transmembrane tyrosine kinase essential for proliferation, differentiation, survival. Small molecule inhibitors targeting result swift effective rodents. Moreover, discontinuation sufficient repopulation. Attention summarizing studies incorporate inhibition Indeed, affects multiple aspects pathophysiology, including neuroinflammation, oxidative stress, functional recovery measurable astrocytes, peripheral cells, neurons. Taken together, data highlight an important sustaining increasing risk which lends to neuronal damage behavioral deficits chronically Ultimately, insights from critical understanding temporospatial develop mediating pathophysiology

Language: Английский

Citations

6
Fundamental Neurochemistry Review: Microglial immunometabolism in traumatic brain injury DOI Creative Commons
Nathan Ryzewski Strogulski, Luis Valmor Portela, Brian M. Polster

et al.

Journal of Neurochemistry, Journal Year: 2023, Volume and Issue: 167(2), P. 129 - 153

Published: Sept. 27, 2023

Abstract Traumatic brain injury (TBI) is a devastating neurological disorder caused by physical impact to the that promotes diffuse damage and chronic neurodegeneration. Key mechanisms believed support secondary include mitochondrial dysfunction neuroinflammation. Microglia brain‐infiltrating macrophages are responsible for neuroinflammatory cytokine reactive oxygen species (ROS) production after TBI. Their associated with loss of homeostatic microglial functions such as immunosurveillance, phagocytosis, immune resolution. Beyond providing energy support, metabolic pathways reprogram pro‐ anti‐inflammatory machinery in cells, critical immunometabolic axis capable regulating immunologic response noxious stimuli. In brain, capacity adapt different environmental stimuli derives, part, from microglia's ability recognize respond changes extracellular intracellular metabolite levels. This met an equally plastic metabolism, altering function. Microglial pro‐inflammatory activation decreased respiration, whereas polarization supported increased oxidative metabolism. These adaptations contribute neuroimmune responses, placing mitochondria central regulator post‐traumatic Although it established profound neurometabolic occur following TBI, key questions related shifts microglia remain unresolved. (a) nature (b) hierarchical positions glycolysis, pentose phosphate pathway, glutaminolysis, lipid oxidation during recovery, (c) how immunometabolism alters phenotypes, culminating non‐resolving this basic neurochemistry review article, we describe contributions detail primary evidence impairments macrophages, discuss major neuroinflammation, set out future directions toward advancing phenotyping image

Language: Английский

Citations

16
LncRNA H19 knockdown promotes neuropathologic and functional recovery via the Nrf2/HO‐1 axis after traumatic brain injury DOI Creative Commons

Qiankang Chen,

Biwu Wu,

Ziyu Shi

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(7)

Published: July 1, 2024

Traumatic brain injury (TBI) stands as a significant concern in public health, frequently leading to enduring neurological deficits. Long non-coding RNA H19 (lncRNA H19) exerts potential regulator role the pathology of injury. This study investigates effects lncRNA knockdown (H19-KD) on pathophysiology TBI and its neuroprotective mechanisms.

Language: Английский

Citations

5
Senolytic treatment diminishes microglia and decreases severity of experimental autoimmune encephalomyelitis DOI Creative Commons
Sienna Drake, Aliyah Zaman,

Christine Gianfelice

et al.

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: Nov. 1, 2024

The role of senescence in disease contexts is complex, however there considerable evidence that depletion senescent cells improves outcomes a variety particularly related to aging, cognition, and neurodegeneration. Much research has shown previously inflammation can promote cellular senescence. Microglia are central nervous system innate immune cell undergo with aging during contribution microglia multiple sclerosis, an inflammatory neurodegenerative disease, not clear, but strongly implicated chronic active lesion pathology, tissue injury, progression. Drugs could specifically eliminate dysregulated sclerosis therefore great interest the field.

Language: Английский

Citations

5
Treating Traumatic Brain Injury with Minocycline DOI Creative Commons
Peter J. Bergold,

Rachel Furhang,

Siobhán Lawless

et al.

Neurotherapeutics, Journal Year: 2023, Volume and Issue: 20(6), P. 1546 - 1564

Published: Sept. 18, 2023

Language: Английский

Citations

11
Traumatic brain injury disrupts state-dependent functional cortical connectivity in a mouse model DOI
Samantha Bottom-Tanzer,

Sofia Corella,

J. Meyer

et al.

Cerebral Cortex, Journal Year: 2024, Volume and Issue: 34(2)

Published: Jan. 31, 2024

Traumatic brain injury (TBI) is the leading cause of death in young people and can cognitive motor dysfunction disruptions functional connectivity between regions. In human TBI patients rodent models TBI, decreased after injury. Recovery associated with improved cognition memory, suggesting an important link outcome. We examined widespread alterations following using simultaneous widefield mesoscale GCaMP7c calcium imaging electrocorticography (ECoG) mice injured controlled cortical impact (CCI) model TBI. Combining CCI provides us unprecedented access to characterize network changes throughout entire cortex over time. Our data demonstrate that profoundly disrupts immediately injury, followed by partial recovery 3 weeks. Examining discrete periods locomotion stillness reveals alters reduces theta power only during behavioral stillness. Together, these findings causes dynamic, state-dependent ECoG activity across cortex.

Language: Английский

Citations

4