👤 John G F Cleland

Brain-derived neurotrophic factor (BDNF) is a protein crucial to the survival, growth, and differentiation of neurons in the brain and spinal cord. BDNF is monitored across many populations as an indicator of one's cardiometabolic disease (CMD) and mental health (MH) risk. Adults living with a traumatic spinal cord injury (tSCI) are at a higher risk of developing CMD and MH issues, with symptoms often going unrecognized. Establishing serum BDNF as a screening tool within the tSCI population has the potential to improve CMD and MH symptom recognition. This systematic review aims to: (1) explore the tSCI literature to determine whether an association exists between serum BDNF, MH, and CMD risk(s); and; (2) identify best-practice BDNF sampling techniques within the tSCI population. A comprehensive search strategy was developed in collaboration with a University Health Network Librarian. Six databases (MEDLINE, Embase, CENTRAL, APA PsycInfo, CINAHL Ultimate, and Web of Science Core Collection) were searched to identify English-language studies published from inception to July 2025. Studies which reported serum BDNF in the tSCI population in addition to either MH or CMD and have three or more human participants with acute or chronic tSCI were included. Duplicate abstracts were removed and the remaining titles and abstracts reviewed and selected for full-text screening. Study quality was assessed for potential risk of bias using Downs and Black Checklist (Clinical Trials), Newcastle-Ottawa Score (Case-Control Study), or Joanna Briggs Institute Checklist (Cross-sectional Study), prior to data extraction. The serum BDNF analytic methods were reviewed in detail. A total of 2,148 potential studies were identified via the searches, of which 631 duplicates were removed, 1,488 abstracts were excluded for inappropriate population, outcome measure, or study design, and 29 articles were selected for full-text screening, with four studies included in the final review. All studies sampled and analyzed serum BDNF. A total of 271 participants (AIS: A-D, NLI: C1-L5), predominantly male (n = 224), with acute (n = 165) and chronic (n = 51) injuries aged 14-75 as well as healthy controls (n = 55) were included. One study investigated the influence of an intervention and three studies were cross-sectional. No identified study included a description or indication of the prevalence for MH conditions or CMD risk factors. Based on the reviewed literature, links between serum BDNF and MH disorders or CMD risk have not yet been established for individuals with acute or chronic tSCI. The selected studies demonstrated no consistent sampling or analysis methods, with limited adherence to prior established standards in the general population, bringing into question the reliability, validity, and quality of the available outcome data. Show less

Heart failure (HF) is associated with cytokine activation and inflammation. Experimental evidence suggests that plasma interleukin-17 (IL-17) is associated with myocardial fibrosis and cardiac dysfunction in HF. IL-17D, a subtype of IL-17 originates from particular tissues such as the heart. However, there is very limited data on the IL-17 cytokine family in patients with HF. Therefore, we investigated the association between circulating IL-17D levels, clinical characteristics and outcome in a large cohort of patients with heart failure. Plasma IL-17D was measured in 2032 patients with HF from 11 European countries using a proximity extension assay. The primary outcome was a composite of HF hospitalization or all-cause mortality. Patients with higher plasma IL-17D concentrations were more likely to have atrial fibrillation (AF), renal dysfunction and heart failure with preserved ejection fraction (HFpEF) and had higher plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations (all p < 0.001). IL-17D was not associated with interleukin-6 (IL-6) or C-reactive protein (CRP) concentrations. After adjustment for confounders in a multivariable Cox regression analysis, patients in the highest quartile of plasma IL-17D had a significantly increased risk of the composite outcome of HF hospitalization or all-cause mortality compared to patients in the lowest quartile [Hazard ratio (HR) 1.28, 95% confidence interval (CI) 1.05-1.57]. In patients with HF, elevated plasma IL-17D concentrations are associated with higher plasma NT-proBNP concentrations and a higher prevalence of AF and renal dysfunction. High IL-17D concentrations are independently associated with worse outcome. Show less

Despite Alzheimer's disease (AD) disproportionately affecting women, the mechanisms remain elusive. In AD, microglia undergo 'metabolic reprogramming', which contributes to microglial dysfunction and AD pathology. However, how sex and age contribute to metabolic reprogramming in microglia is understudied. Here, we use metabolic imaging, transcriptomics, and metabolic assays to probe age- and sex-associated changes in brain and microglial metabolism. Glycolytic and oxidative metabolism in the whole brain was determined using Fluorescence Lifetime Imaging Microscopy (FLIM). Young female brains appeared less glycolytic than male brains, but with aging, the female brain became 'male-like.' Transcriptomic analysis revealed increased expression of disease-associated microglia (DAM) genes (e.g., ApoE, Trem2, LPL), and genes involved in glycolysis and oxidative metabolism in microglia from aged females compared to males. To determine whether estrogen can alter the expression of these genes, BV-2 microglia-like cell lines, which abundantly express DAM genes, were supplemented with 17β-estradiol (E2). E2 supplementation resulted in reduced expression of DAM genes, reduced lipid and cholesterol transport, and substrate-dependent changes in glycolysis and oxidative metabolism. Consistent with the notion that E2 may suppress DAM-associated factors, LPL activity was elevated in the brains of aged female mice. Similarly, DAM gene and protein expression was higher in monocyte-derived microglia-like (MDMi) cells derived from middle-aged females compared to age-matched males and was responsive to E2 supplementation. FLIM analysis of MDMi from young and middle-aged females revealed reduced oxidative metabolism and FAD+ with age. Overall, our findings show that altered metabolism defines age-associated changes in female microglia and suggest that estrogen may inhibit the expression and activity of DAM-associated factors, which may contribute to increased AD risk, especially in post-menopausal women. Show less

Despite Alzheimer's disease (AD) disproportionately affecting women, the mechanisms remain elusive. In AD, microglia undergo 'metabolic reprogramming', which contributes to microglial dysfunction and AD pathology. However, how sex and age contribute to metabolic reprogramming in microglia is understudied. Here, we use metabolic imaging, transcriptomics, and metabolic assays to probe age-and sex-associated changes in brain and microglial metabolism. Glycolytic and oxidative metabolism in the whole brain was determined using Fluorescence Lifetime Imaging Microscopy (FLIM). Young female brains appeared less glycolytic than male brains, but with aging, the female brain became 'male-like.' Transcriptomic analysis revealed increased expression of disease-associated microglia (DAM) genes (e.g., Show less

The HERMES (HEart failure Molecular Epidemiology for Therapeutic targetS) consortium aims to identify the genomic and molecular basis of heart failure. The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of ≥1.10 for common variants (allele frequency ≥ 0.05) and ≥1.20 for low-frequency variants (allele frequency 0.01-0.05) at P < 5 × 10 HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction. Show less