Mapping Inflammatory Markers in Cerebrospinal Fluid Following Aneurysmal Subarachnoid Hemorrhage: An Age- and Sex-Matched Analysis

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1302 - 1302

Published: Feb. 3, 2025

Despite extensive research on aneurysm treatment and neurocritical care, aneurysmal subarachnoid hemorrhage (SAH) is still a life-threatening disease, often leaving survivors with lasting neurological cognitive impairments. Early brain injury (EBI) delayed cerebral ischemia (DCI) are the main contributors to damage, neuroinflammation being critical shared pathophysiological process. While numerous inflammatory markers their temporal profiles in cerebrospinal fluid (CSF) have already been identified, comparisons age- sex-matched controls limited. This study analyzed CSF from 17 SAH patients requiring an external ventricular drain (EVD) due symptomatic hydrocephalus, sampled days 4 10 post-ictus. An control group included cerebrovascularly healthy lumbar drains during aortic surgery. Chemokines cytokines were quantified using immunoassays. Significantly elevated across both time points MCP-1, CXCL-13, Eotaxin-1, CXCL-10, IL-8, MIF. MIP-1α MIP-1β showed significant differences at particular points, indicating distinct profile for each parameter. These findings highlight neuroinflammation’s key role intracranial systemic pathophysiology following SAH, emphasizing its complexity individual variability. Knowing demographic factors impact specific manifestations of processes, comparison meaningful.

Language: Английский

Inflammation-induced lysosomal dysfunction in human iPSC-derived microglia is exacerbated by APOE 4/4 genotype

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: March 28, 2025

Background. The ε4 isoform of apolipoprotein E (ApoE) is the most significant genetic risk factor for Alzheimer’s disease. Glial cells are main source ApoE in brain, and microglia, has been shown to impair mitochondrial metabolism uptake lipids Aβ42. However, whether alters autophagy or lysosomal activity microglia basal inflammatory conditions unknown. Methods. Altogether, microglia-like (iMGs) from eight APOE3/3 six APOE4/4 human induced pluripotent stem cell (iPSC) lines were used this study. responses iMGs Aβ42, LPS IFNγ studied by metabolomics, proteomics, functional assays. Results. Here, we demonstrate that with genotype exhibit reduced level pinocytosis an overall downregulation proteins compared iMGs. Inflammatory stimulation a combination Aβ42 PI3K/AKT/mTORC signaling pathway, increased pinocytosis, blocked autophagic flux, leading accumulation sequestosome 1 both Exposure furthermore caused membrane permeabilization, which was significantly stronger positively correlated secretion proinflammatory chemokine IL-8. Metabolomics analysis indicated dysregulation amino acid metabolism, primarily L-glutamine, Conclusions. Overall, our results suggest inflammation-induced metabolic reprogramming places lysosomes under substantial stress. Lysosomal stress more detrimental defects biogenesis.

Language: Английский

Markers of Inflammation and Hypofibrinolysis Are Associated with Cognitive Dysfunction and Motor Performances in Atrial Fibrillation Patients on Oral Anticoagulant Therapy: Insights from the Strat-AF Study

Biomedicines, Journal Year: 2025, Volume and Issue: 13(4), P. 941 - 941

Published: April 11, 2025

Background: Atrial fibrillation (AF) is the most common supraventricular arrythmia and one of commonly encountered heart conditions in clinical practice. Emerging evidence suggests a significant role inflammation pathogenesis AF. Population studies have also suggested an association between AF cognitive impairment dementia. The aim this study therefore to assess, population patients on oral anticoagulant therapy, circulating biomarkers involved motor performances enrolled patients. Methods: Strat-AF observational, prospective, single-center, hospital-based enrolling elderly with Results refer 180 subjects who underwent complete clinical, biohumoral, cognitive, functional evaluation. Results: At multivariate logistic regression, Clot Lysis Time (CLT) levels von Willebrand Factor (vWF) remained significantly associated pathological at Stroop test (expressed as execution time) [OR 95% CI 1.54 (1.02–2.35), p = 0.042 1.75 (1.08–2.82), 0.023, respectively]. With regard Short Physical Performance Battery (SPPB), IL-8 endpoint 2.19 (1.13–4.25), 0.020]. Conclusions: Our results suggest potential innovative tool able identify risk worse prognosis terms performances. relevance these due fact that we no efficient methods predict deterioration performance and, consequently, possible onset dementia undergoing therapy.

Language: Английский