Mikaela A Drewel, Sarah Schwartz, Gail B Rattinger+2 more · 2026 · The journals of gerontology. Series A, Biological sciences and medical sciences · Oxford University Press · added 2026-04-24
Traumatic brain injury (TBI) is a well-recognized risk factor for late-life cognitive decline. However, few studies have examined individual differences in sex and genetics, which may modify risk. We Show more
Traumatic brain injury (TBI) is a well-recognized risk factor for late-life cognitive decline. However, few studies have examined individual differences in sex and genetics, which may modify risk. We examined sex differences in gene-TBI interactions for dementia risk genes apolipoprotein E (APOE) and selected brain-derived neurotrophic factor (BDNF) single-nucleotide polymorphisms (SNPs) in predicting late-life cognitive decline. We studied 4293 individuals without dementia at baseline (mean age: 74.93, SD: 6.87 years, 57% female). Approximately 25% reported a history of TBI. Linear mixed effects models examined associations between sex, TBI characteristics, APOE genotype, BDNF SNPs and their interactions, with cognitive decline. Compared to males, females experienced fewer TBIs across the lifespan, the majority occurring in late-life. Number of TBI interacted with sex and APOE genotype such that female APOE ε4 allele carriers with multiple TBIs exhibited worse outcomes on global cognition (P < .001; eg, ε4+/TBI2+ estimated marginal means [EMMs] from baseline to year 10 = -17.22 points compared with ε4-/TBI2+ = -7.21), whereas males did not exhibit differential decline by APOE ε4 alleles and TBI number. BDNF Val66Met genotype showed trend-level moderation of TBI history and cognitive decline, with slower decline experienced by heterozygous individuals with multiple TBIs compared with homozygous major allele carriers. There were few significant associations between timing and severity of TBI with cognitive outcomes. These results underscore the importance of considering individual differences of sex and APOE and BDNF-related gene variants on the long-term cognitive effects of TBI. Show less
Traumatic injuries to the central nervous system (CNS), including traumatic brain injury (TBI) and spinal cord injury (TSCI), are among the leading causes of disability and mortality worldwide. The va Show more
Traumatic injuries to the central nervous system (CNS), including traumatic brain injury (TBI) and spinal cord injury (TSCI), are among the leading causes of disability and mortality worldwide. The valuable effect of extracellular vesicles (EVs) from mesenchymal stem cells (MSCs-EVs) in the treatment of traumatic injuries has been documented. EVs, including exosomes, are heterogeneous cell-derived particles, contributing to cell communication through exchanging biomolecules between cells. MSCs-EVs can regulate physiological processes, including synaptic plasticity, neuronal firing, development and repair of myelin sheath, neuroprotection, advancement of neuroinflammation, and extent and elimination of protein aggregates. However, natural MSCs-EVs have some limitations. Recent advancements have shown that MSCs-EVs can be engineered for effective and targeted therapy in traumatic injuries. Most experiments have focused on miRNA-engineered MSCs-EVs to boost their therapeutic effects. In TBI models, MSCs-EVs have been modified to deliver miR-124, miR-17-92, miR-124-3p, or BDNF, whereas in TSCI models, EVs have been engineered with miR-216a-5p, miR-146a-5p, miR-133b, miR-146, miR-138-5p, miR-29b, miR-181c, lncGm37494, siRNAs, or Shh. Results from in vitro and animal studies show the substantial potential of engineered MSCs-EVs for protection, neuroregeneration, and functional recovery. But challenges remain in translating these outcomes into clinical trials, including standardization, safety, and delivery efficacy. In this review, we summarize recent knowledge on MSCs-EVs, focusing on their mechanisms of action in CNS traumatic injuries, and discuss the latest developments, inherent advantages, and potential hurdles in evolving these groundbreaking therapeutic approaches. Show less
To evaluate the relationship between the levels of interleukin (IL)-6 (a marker of inflammation), cortisol (a marker of the hypothalamic-pituitary-adrenal axis functioning), and brain-derived neurotro Show more
To evaluate the relationship between the levels of interleukin (IL)-6 (a marker of inflammation), cortisol (a marker of the hypothalamic-pituitary-adrenal axis functioning), and brain-derived neurotrophic factor (BDNF, a key neurotrophic factor) in acute and long-term (after 1 month) periods of traumatic brain injury (TBI) with trauma characteristics, as well as neurological and mental disorders. Analysis of data from a cohort longitudinal prospective study. Changes over time in IL-6, cortisol, and BDNF levels during the 1 month after injury were described: IL-6 and cortisol decreased, while BDNF increased, reflecting mechanisms of primary injury and secondary recovery processes. In the acute period, levels of IL-6, cortisol, and BDNF correlated with the severity of the patient's condition: low BDNF and high IL-6 and cortisol levels were associated with a more severe injury, as assessed by the Glasgow Coma Scale. An association between these markers and the presence of amnesia and abnormal EEG changes in the acute period of TBI was found. IL-6, cortisol, and BDNF are important pathophysiological markers of TBI associated with both immediate features of TBI and its complications. Show less