Blood-based biomarkers of cerebral small vessel disease

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 95, P. 102247 - 102247

Published: Feb. 27, 2024

Age-associated cerebral small vessel disease (CSVD) represents a clinically heterogenous condition, arising from diverse microvascular mechanisms. These lead to chronic cerebrovascular dysfunction and carry substantial risk of subsequent stroke vascular cognitive impairment in aging populations. Owing advances neuroimaging, vivo visualization vasculature abnormities detection CSVD, including lacunes, microinfarcts, microbleeds white matter lesions, is now possible, but remains resource-, skills- time-intensive approach. As result, there has been recent proliferation blood-based biomarker studies for CSVD aimed at developing accessible screening tools early stratification. However, good understanding the pathophysiological processes underpinning needed identify assess useful biomarkers. Here, we provide an overview associated with pathogenesis, endothelial injury dysfunction, neuroinflammation, oxidative stress, perivascular neuronal damage as well cardiovascular dysfunction. Then, review clinical key biomolecules involved aforementioned processes. Lastly, outline future trends directions discovery validation.

Language: Английский

---

Inflammatory Effects and Regulatory Mechanisms of Chitinase-3-like-1 in Multiple Human Body Systems: A Comprehensive Review

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(24), P. 13437 - 13437

Published: Dec. 15, 2024

Chitinase-3-like-1 (Chi3l1), also known as YKL-40 or BRP-39, is a highly conserved mammalian chitinase with chitin-binding ability but no enzymatic activity. Chi3l1 secreted by various cell types and induced several inflammatory cytokines. It can mediate series of biological processes, such proliferation, apoptosis, migration, differentiation, polarization. Accumulating evidence has verified that involved in diverse conditions; however, systematic comprehensive understanding the roles mechanisms almost all human body system-related diseases still lacking. The consists ten organ systems, which are combinations multiple organs perform one more physiological functions. Abnormalities these systems trigger environments, posing serious threats to quality life lifespan humans. Therefore, exploring novel reliable biomarkers for important, being parameter because its pathophysiological development diseases. Reportedly, plays an important role diagnosing determining disease activity/severity/prognosis related system inflammation disorders. Additionally, many studies have revealed influencing factors regulatory (e.g., ERK MAPK pathways) conditions, identifying potential therapeutic targets In this review, we comprehensively summarize underlying disorders respiratory, digestive, circulatory, nervous, urinary, endocrine, skeletal, muscular, reproductive provides Moreover, article summarizes strategies on basis mediated Chi3l1.

Language: Английский

---

Characterization of Chitinase 3-like protein 1 spatiotemporal distribution in human post-traumatic brain contusions and other neuropathological scenarios

Journal of Neuropathology & Experimental Neurology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 20, 2025

Abstract Chitinase 3-like protein 1 (CHI3L1) is emerging as a promising biomarker for assessing intracranial lesion burden and predicting prognosis in traumatic brain injury (TBI) patients. Following experimental TBI, Chi3l1 transcripts were detected reactive astrocytes located within the pericontusional cortex. However, cellular sources of CHI3L1 response to hemorrhagic contusions human remain unidentified. Hence, we examined comprehensive collection histologically defined acute subacute cerebral with various surgical intervals using immunohistochemistry, validated through double immunofluorescence markers such GFAP, NeuN, MBP, Iba-1, along Fluoro-Jade C histofluorescence staining. was found at meningeal interfaces, showing significant thickening subpial glial plate. Paradoxically, CHI3L1-positive identified neuroanatomical locations distant from foci, where numerous eosinophilic ischemic neurons also exhibited immunoreactivity. immunostaining extended into white matter tracts highlighted phagocytic or activated microglia forms after delayed decompressions. Given these findings, advise against astrogliosis marker due its expression multiple cell types, including astrocytes, neurons, oligodendrocytes, ependymocytes, leptomeningeal cells, microglia, blood vessels. This non-selective underscores potential elevation patterns biofluids reflect overall extent.

Language: Английский

---

Chitinase-3 Like-Protein-1 Signature in Neurological Disorders: Emphasis on Stroke

Journal of Molecular Neuroscience, Journal Year: 2025, Volume and Issue: 75(1)

Published: Feb. 20, 2025

Language: Английский

---

The neutrophil-to-lymphocyte ratio is associated with functional outcome among single small subcortical infarction: Mediating effects of white matter hyperintensities

Journal of Stroke and Cerebrovascular Diseases, Journal Year: 2025, Volume and Issue: unknown, P. 108341 - 108341

Published: May 1, 2025

Increasing evidence indicated that neutrophil-to-lymphocyte ratio (NLR) was correlated with unfavorable functional outcome in ischemic stroke. However, limited studies have explored the relationship between NLR and single small subcortical infarction (SSSI). This study aims to investigate link patients SSSI assess whether white matter hyperintensities (WMH) mediates prognosis. research analyzed data from a Chinese cohort study. The primary (modified Rankin Scale score of 2-6) at 90 days after stroke onset, secondary discharge. using restricted cubic spline (RCS) multivariable logistic regression. A mediation analysis conducted examine mediated by WMH. Among 513 included study, seen 145 (28.3%) 90-day follow-up 156 (30.4%) After controlling for confounding variables, elevated levels were found be linked both Mediation analyses overall WMH significantly discharge, proportions 29.6% 24.2%, respectively. Periventricular accounted 36.4% 32.1% effects, Elevated independently increased risk individuals SSSI. In SSSI, partially outcome.

Language: Английский

---

Cerebrospinal fluid YKL‐40 relates to white matter hyperintensity progression in females but not males over a 6‐year period

Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring, Journal Year: 2025, Volume and Issue: 17(2)

Published: April 1, 2025

Abstract INTRODUCTION Neuroinflammation may have sex‐specific effects on white matter injury and impact the development of dementia. METHODS Human chitinase‐3‐like protein‐1 (YKL‐40) concentrations at baseline were related to hyperintensity (WMH) volume, free water (FW), FW‐corrected fractional anisotropy using linear models (for cross‐sectional outcomes) mixed‐effects longitudinal outcomes), adjusting for demographic medical risk factors. Models repeated with a sex‐interaction term then stratified by sex. RESULTS In analyses, greater YKL‐40 associated increased WMHs in females but not males parietal (females p = 0.04; .34) temporal lobes 0.005; 0.71) longitudinally. associations FW null. DISCUSSION Results suggest that neuroinflammation is driver (but FW) females. Differential sequelae be one reason burden WMHs. Highlights Cerebrospinal fluid hyperintensities cross‐sectionally Longitudinally, cerebrospinal lobes, regions exhibit early pathological changes Alzheimer's disease . microstructural measures.

Language: Английский

---

Glial Fibrillary Acidic Protein as a Potential Indicator for Symptomatic Intracranial Hemorrhage in Acute Ischemic Patients Undergoing Endovascular Thrombectomy

Clinical Interventions in Aging, Journal Year: 2024, Volume and Issue: Volume 19, P. 123 - 132

Published: Jan. 1, 2024

Background: The correlation between glial fibrillary acidic protein (GFAP) and symptomatic intracranial hemorrhage (sICH) in acute ischemic stroke (AIS) patients undergoing endovascular thrombectomy (EVT) treatment remains uncertain. We aimed to assess the association levels of GFAP bloodstream occurrence sICH. Methods: Between June 2019 May 2023, 142 consecutive AIS EVT at Stroke Center 35 controls from Physical Examination were retrospectively included. quantified using enzyme-linked immunosorbent assay prior (T1) 24 h after procedure (T2). identification sICH was based on Heidelberg Bleeding Classification. Results: Serum T1 significantly higher than those (0.249 [0.150– 0.576] versus 0.065 [0.041– 0.110] ng/mL, p = 0.001), there a notably elevation T2 compared (3.813 [1.474, 5.876] 0.249 0.001). Of patients, 18 (14.5%) had EVT. showed significant associations with both unadjusted model (OR 1.513, 95% CI 1.269– 1.805, 0.001) multivariable adjusted 1.518, 1.153– 2.000, 0.003). Furthermore, addition conventional resulted enhancement risk reclassification for (integrated discrimination improvement [IDI] 0.183, 0.070– 0.295, Conclusion: increased Elevated correlated an elevated could potentially serve as dependable indicator individuals who treated Keywords: protein, stroke, hemorrhage, indicator,

Language: Английский

---

Association between Citrullinated Histone H3 and White Matter Lesions Burden in Patients with Ischemic Stroke

Brain Sciences, Journal Year: 2023, Volume and Issue: 13(7), P. 991 - 991

Published: June 24, 2023

Introduction: Neutrophil extracellular traps play a role in the pathophysiology of stroke and are associated with severity mortality. We aimed to investigate whether citrullinated histone H3 (CitH3), biomarker for neutrophil formation, is white matter lesion (WML) burden ischemic patients. Methods: Between September 2021 April 2022, 322 patients were enrolled this prospective observational cohort study. Serum CitH3 levels measured after admission using an enzyme-linked immunosorbent assay. WMLs was graded according Fazekas scale conceptually defined as mild (total score 0–2) severe 3–6). used multivariable regression models determine relationship between concentrations burden. Results: One-hundred forty-eight (46.0%) diagnosed admission. Increased (first quartile vs. fourth H3Cit, odds ratio, 3.311, 95% confidence interval, 1.336–8.027; p = 0.011) independently greater WML fully adjusted model. Similar results found when H3Cit analyzed continuous variable. Furthermore, multiple-adjusted spline model showed linear association (P 0.001 linearity). Conclusions: In present study, increased positively extensive patients, indicating formation pathogenesis WMLs.

Language: Английский

---

Higher High-Mobility Group Box-1 Levels are Associated with White Matter Lesions in Ischemic Stroke Patients

Journal of Inflammation Research, Journal Year: 2023, Volume and Issue: Volume 16, P. 4441 - 4449

Published: Oct. 1, 2023

High-mobility group box-1 (HMGB1) is a useful biomarker for disease severity stratification and prognosis prediction. We aim to explore whether the circulating HMGB1 concentrations are associated with white matter lesions (WMLs) burden in stroke patients.Between 2022 June December 2022, patients acute ischemic were prospectively enrolled. levels measured by an enzyme-linked immunosorbent assay after admission all patients. The WMLs was assessed Fazekas scale. dichotomized into those moderate-severe (Fazekas score 3-6) versus none-mild 0-2). Furthermore, based on of periventricular (PWMLs) deep (DWMLs), categorized as 0-1) or 2-3).A total 287 participants (mean age: 64.9 years; 157 male) analyzed. median serum 7.3 ng/mL (interquartile, 4.3 ng/mL-12.3 ng/mL). After adjustment potential confounders, elevated presence (first quartile vs fourth quartile, odds ratio [OR], 4.101; 95% confidence interval [CI], 1.948-8.633; P = 0.001) PWMLs OR, 9.181; CI, 4.078-20.671; 0.001). Similar results found when analyzed continuous variable.This study demonstrated that increased WMLs, mainly region.

Language: Английский

---

Ophthalmic Artery Morphology and Hemodynamics Associated with White Matter Hyperintensity

International Journal of Medical Sciences, Journal Year: 2024, Volume and Issue: 21(9), P. 1604 - 1611

Published: Jan. 1, 2024

To investigate morphological and hemodynamic characteristics of the ophthalmic artery (OA) in patients with white matter hyperintensity (WMH), association presence severity WMH OA characteristics.

Language: Английский

---