Brain Behavior and Immunity, Journal Year: 2022, Volume and Issue: 108, P. 221 - 232
Published: Dec. 6, 2022
Language: Английский
Frontiers in Molecular Biosciences, Journal Year: 2021, Volume and Issue: 8
Published: Dec. 14, 2021
Cancer-related cognitive impairment (CRCI) is a frequent side effect experienced by an increasing number of cancer survivors with significant impact on their quality life. Different definitions and means evaluation have been used in available literature; hence the exact incidence CRCI remains unknown. can be described as symptoms reported patients self-reported questionnaires or changes evaluated formal neuropsychological tests. Nevertheless, association between objectively assessed relatively weak absent. Studies focused especially breast patients, but has multiple types cancer, including colorectal, lung, ovarian, prostate, testicular hematological malignancies. While associated various treatment modalities, radiotherapy, chemotherapy, hormone therapy novel systemic therapies, it also detected prior to treatment. Therefore, effects itself without psychological distress may involved pathogenesis result altered coping mechanisms after diagnosis. The development probably multifactorial are currently not completely understood. Possible risk factors include administered treatment, genetic predisposition, age such anxiety, depression fatigue. Multiple suggested responsible for CRCI, direct neurotoxic injury radiation while other indirect contributing hypothesized. Chronic neuroinflammation mediated active innate immune system, DNA-damage endothelial dysfunction hypothesized central mechanism pathogenesis. There evidence potential plasma (e.g., damage molecular patterns, inflammatory components, circulating microRNAs, exosomes, short-chain fatty acids, others), cerebrospinal fluid radiological biomarkers patients. Discovery crucial early identification at increased strategies lower burden long-term This review summarizes current literature focus different treatments, possible factors, promising biomarkers.
Language: Английский
Citations
103
Trends in Neurosciences, Journal Year: 2021, Volume and Issue: 44(6), P. 441 - 451
Published: March 2, 2021
Language: Английский
Citations
75
Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13
Published: Nov. 16, 2022
Ischemic stroke (IS) is one of the major types cerebrovascular diseases causing neurological morbidity and mortality worldwide. In pathophysiological process IS, microglia play a beneficial role in tissue repair. However, it could also cause cellular damage, consequently leading to cell death. Inflammation characterized by activation microglia, increasing evidence showed that autophagy interacts with inflammation through regulating correlative mediators signaling pathways. this paper, we summarized harmful effects IS. addition, discussed interplay between ischemic inflammation, as along its application treatment We believe help provide theoretical references for further study into IS treatments future.
Language: Английский
Citations
57
Neurotherapeutics, Journal Year: 2021, Volume and Issue: 18(3), P. 2107 - 2125
Published: July 1, 2021
Language: Английский
Citations
56
Neuro-Oncology, Journal Year: 2022, Volume and Issue: 25(5), P. 927 - 939
Published: Nov. 5, 2022
Ultrahigh dose-rate radiotherapy (FLASH-RT) affords improvements in the therapeutic index by minimizing normal tissue toxicities without compromising antitumor efficacy compared to conventional (CONV-RT). To investigate translational potential of FLASH-RT a human pediatric medulloblastoma brain tumor, we used radiosensitive juvenile mouse model assess adverse long-term neurological outcomes.Cohorts 3-week-old male and female C57Bl/6 mice exposed hypofractionated (2 × 10 Gy, or CONV-RT) whole irradiation unirradiated controls underwent behavioral testing ascertain cognitive status four months posttreatment. Animals were sacrificed 6 post-irradiation tissues analyzed for cerebrovascular decrements.The impact was over 6-month follow-up. ameliorated neurocognitive decrements induced CONV-RT preserved synaptic plasticity integrity at electrophysiological (long-term potentiation), molecular (synaptophysin), structural (Bassoon/Homer-1 bouton) levels multiple regions. The benefits also linked reduced neuroinflammation (activated microglia) preservation structure, maintaining aquaporin-4 microglia colocalized vessels.Hypofractionated significant protection when CONV-RT. capability preserve critical outcomes properties 6-months is noteworthy highlights its resolving long-standing complications faced tumor survivors. While care must be exercised before clinical translation realized, present findings document marked that extend from synapse cognition microvasculature.
Language: Английский
Citations
39
Experimental Neurology, Journal Year: 2019, Volume and Issue: 318, P. 32 - 41
Published: April 25, 2019
Language: Английский
Citations
72
Cancer Research, Journal Year: 2020, Volume and Issue: 81(7), P. 1732 - 1744
Published: Dec. 15, 2020
Abstract The adverse neurocognitive sequelae following clinical radiotherapy (RT) for central nervous system (CNS) malignancies are often long-lasting without any recourse. Despite recent progress, the cellular mechanisms mediating RT-induced cognitive deficits (RICD) poorly understood. complement is an immediate sensor of a disturbed inflammatory environment and potent mediator gliosis with range nonimmune functions in CNS, including synaptic pruning, which detrimental if dysregulated. We hypothesize that complement-mediated changes glial cell function significantly contribute to RICD. underlying alterations CNS cascade proteins (C1q, C3), TLR4, colabeling glia (IBA1, GFAP) were examined using gene expression, immunofluorescence, silico modeling approaches adult mouse brain 9 Gy cranial RT. Three-dimensional volumetric quantification showed elevated molecular signatures at short- long-term post-RT times. found significant elevations C1q, C3, TLR4 accompanied by increased astrocytes microglia. To address mechanism activation, neuroinflammation, dysfunction, we used genetic approach—conditional, microglia-selective C1q (Flox) knockdown mice—to determine whether glia-specific, upstream contributes C1q-Flox mice exposed RT no compared irradiated WT mice. Further, protected from microglial activation loss, elevation anaphylatoxin C5a receptor, astrocytic-C3, microglial-TLR4 expression brain. Our findings demonstrate first time microglia-specific RICD involving component, C1q. Significance: Clinically-relevant induces aberrant leading injury. Microglia-selective deletion ameliorates radiation-induced impairments, highlighting potential as novel therapeutic target. See related commentary Korimerla Wahl, p. 1635
Language: Английский
Citations
53
Journal of Neuroinflammation, Journal Year: 2020, Volume and Issue: 17(1)
Published: May 19, 2020
Abstract Background Cosmic radiation exposures have been found to elicit cognitive impairments involving a wide-range of underlying neuropathology including elevated oxidative stress, neural stem cell loss, and compromised neuronal architecture. Cognitive also associated with sustained microglia activation following low dose exposure helium ions. Space-relevant charged particles neuroinflammation that persists long-term post-irradiation. Here, we investigated the potential neurocognitive benefits depletion whole body Methods Adult mice were administered dietary inhibitor (PLX5622) colony stimulating factor-1 receptor (CSF1R) deplete 2 weeks after irradiation ( 4 He, 30 cGy, 400 MeV/n). Cohorts maintained on normal PLX5622 diet tested for function using seven independent behavioral tasks, microglial activation, hippocampal morphology, spine density, electrophysiology properties 4–6 later. Results treatment caused rapid near complete elimination in brain within 3 days treatment. Irradiated animals exhibited range deficits medial pre-frontal cortex hippocampus increased activation. Animals no radiation-induced deficits, expression resting activated almost completely abolished, without any effects oligodendrocyte progenitors, throughout brain. While was attenuate increases post-synaptic density protein 95 (PSD-95) puncta preserve mushroom type densities, other morphologic features neurons electrophysiologic measures intrinsic excitability relatively unaffected. Conclusions Our data suggest play critical role cosmic and, approaches targeting are poised provide considerable benefit exposed particles.
Language: Английский
Citations
50
Neurochemical Research, Journal Year: 2021, Volume and Issue: 46(12), P. 3247 - 3263
Published: Aug. 17, 2021
Language: Английский
Citations
44
International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(15), P. 8286 - 8286
Published: July 27, 2022
Radiation-induced brain injury (RIBI) after radiotherapy has become an increasingly important factor affecting the prognosis of patients with head and neck tumor. With delivery high doses radiation to tissue, microglia rapidly transit a pro-inflammatory phenotype, upregulate phagocytic machinery, reduce release neurotrophic factors. Persistently activated mediate progression chronic neuroinflammation, which may inhibit neurogenesis leading occurrence neurocognitive disorders at advanced stage RIBI. Fully understanding microglial pathophysiology cellular molecular mechanisms irradiation facilitate development novel therapy by targeting prevent RIBI subsequent neurological neuropsychiatric disorders.
Language: Английский
Citations
37