Free-heme induces neuroinflammation and cognitive impairment by microglial activation via the TLR4/MyD88/NF-kB signaling pathway DOI Creative Commons
Xin Wei, Fan Zhang, Dan Cheng

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 9, 2023

Abstract Background: Red blood cells (RBCs) transfusion is related to perioperative neurocognitive disorders. The toxic effect of free-heme has been identified in many pathologies. However, the underlying mechanisms RBCs or cognitive impairment have not clearly explored. Therefore, this research was conducted determine mechanism heme-induced neuroinflammation and impairment. Methods: Rats were received intraperitoneal injection hemin alone combined with intracerebroventricular Hemopexin (HPX), MWM test measure function. elimination condition heme-HPX complexes evaluated by flow cytometry for CD91+ cells. microglial inflammatory response rat brain BV2 observed immunofluorescence staining Iba-1 ELISA analysis TNF-α, IL-1β IL-6. Furthermore, neuronal apoptosis HT22 + coculture system detected staining. Finally, western blot detect TLR4/MyD88/NF-kB proteins treated pathway inhibitors. Additionally, M1 surface marker CD86 further confirm neuroinflammation. Results: Intraperitoneal induced impairment, increase cells, up-regulation TNF-α IL-1β, down-regulation IL-6, activation microglia, signaling brain. Significantly, HPX reduced above effects. Hemin boost IL-6 as well Notably, when cocultured significantly increased. also increased inhibiting responses. Conclusions : Free-heme induces may involve inflammation via pathway. potential therapeutic

Language: Английский

Free heme induces neuroinflammation and cognitive impairment by microglial activation via the TLR4/MyD88/NF-κB signaling pathway DOI Creative Commons
Xin Wei, Fan Zhang, Dan Cheng

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Jan. 5, 2024

Abstract Background Red blood cells (RBCs) transfusion is related to perioperative neurocognitive disorders. The toxic effect of free heme has been identified in many pathologies. However, the underlying mechanisms RBCs or cognitive impairment have not clearly explored. Therefore, this research was conducted determine mechanism heme-induced neuroinflammation and impairment. Methods Rats were received intraperitoneal injection hemin alone combined with intracerebroventricular Hemopexin (HPX), MWM test measure function. amount heme-HPX complexes evaluated by flow cytometry for CD91 + cells. microglial inflammatory response rat brain observed immunofluorescence staining Iba-1, factors TNF-α, IL-1β IL-6 BV2 detected ELISA analysis. Furthermore, neuronal apoptosis HT22 coculture system staining. Finally, western blot detect TLR4/MyD88/NF-κB proteins treated pathway inhibitors. Additionally, M1 surface marker CD86 further confirm neuroinflammation. Results Intraperitoneal induced impairment, increase cells, up-regulation TNF-α IL-1β, down-regulation IL-6, activation microglia, signaling brain. Significantly, HPX reduced above effects. Hemin boost as well Notably, when cocultured significantly increased. also increased inhibiting responses. Conclusions Free induces may involve inflammation via pathway. potential therapeutic

Language: Английский

Citations

11
Proposing Bromo-epi-androsterone (BEA) for perioperative neurocognitive disorders with Interleukin-6 as a druggable target DOI Creative Commons
Coad Thomas Dow,

Zade Kidess

Journal of Clinical Anesthesia, Journal Year: 2025, Volume and Issue: 101, P. 111736 - 111736

Published: Jan. 1, 2025

Cognitive impairment following surgery is a significant complication, affecting multiple neurocognitive domains. The term "perioperative disorders" (PND) recommended to encompass this entity. Individuals who develop PND are typically older and have increases in serum brain pro-inflammatory cytokines notwithstanding the type of undergone. Surgical trauma induces production small biomolecules, damage-associated molecular patterns (DAMP), particularly DAMP known as high group box 1 protein (HMGB1). Mechanistically, peripheral surgical promotes that stimulate central nervous system (CNS) inflammation by disrupting blood-brain barrier (BBB) causing functional neuronal disruption leads PND. strongly linked elevations CNS interleukin-1 beta (IL-1β), interleukin-6 (IL-6) tumor necrosis factor alpha (TNFα); these cause further release HMGB1 creating positive feedback loop amplifies inflammatory response. cytokine IL-6 necessary sufficient for Dehydroepiandrosterone (DHEA) principal component steroid metabolome involved immune homeostasis. DHEA has been shown suppress expression several regulation NF-kB pathway. Bromo-epi-androsterone (BEA) potent synthetic analog DHEA; unlike DHEA, it non-androgenic, non-anabolic an effective modulator dysregulation. In randomized, placebo-controlled clinical trial, BEA effected sustained decreases IL-1β, TNFα IL-6. This article presents potential candidate trials targeting suggests use elective total hip arthroplasty well-documented entity relevant management

Language: Английский

Citations

1
Association between surgical admissions, cognition, and neurodegeneration in older people: a population-based study from the UK Biobank DOI Creative Commons
Jennifer Taylor, Kristy Robledo, Vicente Medel

et al.

The Lancet Healthy Longevity, Journal Year: 2024, Volume and Issue: 5(9), P. 100623 - 100623

Published: Sept. 1, 2024

Previous studies have shown that major surgical and medical hospital admissions are associated with cognitive decline in older people (aged 40-69 years at recruitment), which is concerning for patients caregivers. We aimed to validate these findings a large cohort investigate associations neurodegeneration using MRI.

Language: Английский

Citations

6
Mechanisms of perioperative neuronal injury and the search for therapies DOI
Timothy J Marshall, Leiv Otto Watne, Robert D. Sanders

et al.

British Journal of Anaesthesia, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
Effect of combination of multiple anti-inflammatory drugs strategy on postoperative delirium among older patients undergoing hip fracture surgery: a pilot randomized controlled trial DOI Creative Commons

Ayixia Nawan,

Zilong Wu,

Bailin Jiang

et al.

BMC Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 21, 2025

Abstract Background Postoperative delirium is the most common complication in older patients and associated with surgery-induced inflammation. Although inflammation plays a key role delirium, potential benefits of comprehensive anti-inflammatory approach to managing perioperative systemic remain underexplored. This study evaluated whether bundle strategy, combining dexmedetomidine, glucocorticoids, ulinastatin, nonsteroidal drugs, reduces risk postoperative undergoing hip fracture surgery. Methods dual-center, double-blind, placebo-controlled, parallel-group, pilot was conducted from August 2023 January 2024 at two tertiary university hospitals. A total 132 aged ≥ 65 years an American Society Anesthesiologists physical status 2 or 3 scheduled for elective surgery were screened randomized receive either drug placebo. The primary outcome identified within first three days. blood inflammatory markers acute pain measured mediation analysis. Results Of randomized, 123 (93%) completed trial (mean age, 82 years; 75% women). prevalence significantly lower group (15%, 9/62) compared placebo (44%, 27/61) (risk difference, − 30 percentage points [95% CI, 45 15]; relative [RR], 0.33 0.17 0.64]; P = 0.001). No major adverse events reported group. CRP level (predicted mean difference: 29.4 CI: 46.5, 12.2] mg·L −1 ; adjusted < Mediation analysis showed significant indirect association between through reduced (odds ratio [OR], 0.61 0.26 0.87]). Conclusions demonstrates that surgery, without side effects. Systemic mediates protective effect intervention. These findings provide preliminary evidence supporting paving way large-scale multicenter trials optimize prevention strategies. Trial registration registered Chinese Clinical Registry (ChiCTR2300074303) by Ayixia Nawan on 3, 2023, prior patient enrollment.

Language: Английский

Citations

0
Association of peripheral B cells and delirium: combined single-cell sequencing and Mendelian randomization analysis DOI Creative Commons
Siyou Tan, Sining Pan, Lai Wei

et al.

Frontiers in Neurology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 6, 2024

Background Delirium seriously affects the prognosis of patients and greatly reduces ability to work live. Peripheral inflammatory events may contribute development delirium, mechanism which is still unclear. There a lack effective diagnostic treatments for delirium in clinical practice. The study aims investigate alterations peripheral immune cell subsets under stress explore causal associations with delirium. Methods Single-cell transcriptional sequencing data human blood mononuclear cells (PBMC) before after lipopolysaccharide (LPS) intervention were processed by Seurat package R software. PBMC cellular markers defined downscaling clustering Harmony algorithm identify characteristic context stress. Subsequently, two-sample Mendelian randomization (MR) was used these inflammation-related their molecular phenotypes Based on publicly available genetic data, incorporated 70 PBMC-associated traits, including 8 types circulating cells, 33 B phenotypes, 13 T subsets, 16 cell-associated cytokines. results also validated robustness, heterogeneity, horizontal pleiotropy. Results Under LPS-induced stress, monocytes, dendritic showed significant activation quantitative changes. Of these, only lymphocyte counts causally associated risk. This risk link seen TNF pathway. Further studies revealed that this association be related unswitched memory CD27 expressed cells. Annotation screened SNPs polymorphisms CD40 annotated rs25680 rs9883798, respectively. functions key genes regulation responses, differentiation, proliferation, intercellular interactions. Conclusion present potential possibility cell, subset, TNF-related molecules involved due inflammation, can provide clues further investigation prevention treatment strategies.

Language: Английский

Citations

3
Improved early postoperative cognition in elderly gastrointestinal patients: a randomized controlled trial on the role of ultrasound-guided stellate ganglion block DOI Creative Commons

Ruyue Xue,

Yuexian Li,

Mei Zhan

et al.

Frontiers in Aging Neuroscience, Journal Year: 2025, Volume and Issue: 17

Published: Feb. 11, 2025

Background This study evaluates the impact of ultrasound-guided stellate ganglion block (SGB) on early postoperative cognitive dysfunction (POCD) in elderly patients who underwent laparoscopic gastrointestinal (GI) surgery, as well its potential effect oxidative stress and inflammatory responses. Methods In this randomized controlled trial, 104 scheduled for elective GI surgery were to receive SGB before general anesthesia (SGB group) or alone (control group). A total 98 completed study. Cognitive function was assessed using Mini-Mental State Examination (MMSE) Montreal Assessment (MoCA) preoperatively, days one three. The perioperative recordings included mean arterial pressure, heart rate, bispectral index. Blood samples analyzed interleukin-6 (IL-6), superoxide dismutase (SOD), malondialdehyde (MDA). Results group had a significantly lower incidence POCD day ( p &lt; 0.05). IL-6 MDA levels lower, while SOD higher group, when compared control notably three Both groups showed significant changes IL-6, levels, preoperative values. hemodynamic indicators slight reduction intraoperative blood pressure decreased numerical rating scale scores first without differences other indicators. Conclusion Preoperative reduces undergo possibly through inhibition

Language: Английский

Citations

0
The Role of Cytokines in Perioperative Neurocognitive Disorders: A Review in the Context of Anesthetic Care DOI Creative Commons
Hyun Jung Koh, Jin Joo

Biomedicines, Journal Year: 2025, Volume and Issue: 13(2), P. 506 - 506

Published: Feb. 18, 2025

Perioperative neurocognitive disorders (PNDs), including postoperative delirium, delayed recovery, and long-term disorders, present significant challenges for older patients undergoing surgery. Inflammation is a protective mechanism triggered in response to external pathogens or cellular damage. Historically, the central nervous system (CNS) was considered immunoprivileged due presence of blood-brain barrier (BBB), which serves as physical preventing systemic inflammatory changes from influencing CNS. However, aseptic surgical trauma now recognized induce localized inflammation at site, further exacerbated by release peripheral pro-inflammatory cytokines, can compromise BBB integrity. This breakdown facilitates activation microglia, initiating cascade neuroinflammatory responses that may contribute onset PNDs. review explores mechanisms underlying neuroinflammation, with particular focus on pivotal role cytokines pathogenesis

Language: Английский

Citations

0
Preoperative gut microbiota of POCD patients induces pre- and postoperative cognitive impairment and systemic inflammation in rats DOI Creative Commons
Xin Wei, Fei Xing, Yao‐Wei Xu

et al.

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

Published: Sept. 12, 2024

Language: Английский

Citations

3
The Effect of Low-Dose Dexmedetomidine on Perioperative Neurocognitive Dysfunction in Elderly Patients Undergoing Endoscopic Retrograde Cholangiopancreatography (ERCP): A Randomized, Controlled, Double-Blind Trial DOI Creative Commons
Zhangnan Sun,

Ji Min Shi,

Chaolei Liu

et al.

Drug Design Development and Therapy, Journal Year: 2024, Volume and Issue: Volume 18, P. 3715 - 3725

Published: Aug. 1, 2024

This study investigates the effect of low-dose dexmedetomidine infusion on perioperative neurocognitive function in elderly patients undergoing endoscopic retrograde cholangiopancreatography (ERCP).

Language: Английский

Citations

2