MicroRNAs as Potential Biomarkers of Post-Traumatic Epileptogenesis: A Systematic Review.

Structural or post-traumatic epilepsy often develops after brain tissue damage caused by traumatic brain injury, stroke, infectious diseases of the brain, etc. Most often, between the initiating event and epilepsy, there is a period without seizures-a latent period. At this time, the process of restructuring of neural networks begins, leading to the formation of epileptiform activity, called epileptogenesis. The prediction of the development of the epileptogenic process is currently an urgent and difficult task. MicroRNAs are inexpensive and minimally invasive biomarkers of biological and pathological processes. The aim of this study is to evaluate the predictive ability of microRNAs to detect the risk of epileptogenesis. In this study, we conducted a systematic search on the MDPI, PubMed, ScienceDirect, and Web of Science platforms. We analyzed publications that studied the aberrant expression of circulating microRNAs in epilepsy, traumatic brain injury, and ischemic stroke in order to search for microRNAs-potential biomarkers for predicting epileptogenesis. Thus, 31 manuscripts examining biomarkers of epilepsy, 19 manuscripts examining biomarkers of traumatic brain injury, and 48 manuscripts examining biomarkers of ischemic stroke based on circulating miRNAs were analyzed. Three miRNAs were studied: miR-21, miR-181a, and miR-155. The findings showed that miR-21 and miR-155 are associated with cell proliferation and apoptosis, and miR-181a is associated with protein modifications. These miRNAs are not strictly specific, but they are involved in processes that may be indirectly associated with epileptogenesis. Also, these microRNAs may be of interest when they are studied in a cohort with each other and with other microRNAs. To further study the microRNA-based biomarkers of epileptogenesis, many factors must be taken into account: the time of sampling, the type of biological fluid, and other nuances. Currently, there is a need for more in-depth and prolonged studies of epileptogenesis.

Sleep-Disordered Breathing and Prognosis after Ischemic Stroke: It Is Not Apnea-Hypopnea Index That Matters.

BACKGROUND: Sleep-disordered breathing (SDB) is highly prevalent after stroke and is considered to be a risk factor for poor post-stroke outcomes. The aim of this observational study was to evaluate the effect of nocturnal respiratory-related indices based on nocturnal respiratory polygraphy on clinical outcomes (including mortality and non-fatal events) in patients with ischemic stroke. METHODS: A total of 328 consecutive patients (181 (55%) males, mean age 65.8 ± 11.2 years old) with confirmed ischemic stroke admitted to a stroke unit within 24 h after stroke onset were included in the analysis. All patients underwent standard diagnostic and treatment procedures, and sleep polygraphy was performed within the clinical routine in the first 72 h after admission. The long-term outcomes were assessed by cumulative endpoint (death of any cause, new non-fatal myocardial infarction, new non-fatal stroke/transient ischemic attack, emergency revascularization, emergency hospitalization due to the worsening of cardiovascular disease). A Cox-regression analysis was applied to evaluate the effects of nocturnal respiratory indices on survival. RESULTS: The mean follow-up period comprised 12 months (maximal-48 months). Patients with unfavourable outcomes demonstrated a higher obstructive apnea-hypopnea index, a higher hypoxemia burden assessed as a percent of the time with SpO2 < 90%, a higher average desaturation drop, and a higher respiratory rate at night. Survival time was significantly lower (30.6 (26.5; 34.7) versus 37.9 (34.2; 41.6) months (Log Rank 6.857, p = 0.009)) in patients with higher hypoxemia burden (SpO2 < 90% during ≥2.1% versus <2.1% of total analyzed time). However, survival time did not differ depending on the SDB presence assessed by AHI thresholds (either ≥5 or ≥15/h). The multivariable Cox proportional hazards regression (backward stepwise analysis) model demonstrated that the parameters of hypoxemia burden were significantly associated with survival time, independent of age, stroke severity, stroke-related medical interventions, comorbidities, and laboratory tests. CONCLUSION: Our study demonstrates that the indices of hypoxemia burden have additional independent predictive value for long-term outcomes (mortality and non-fatal cardiovascular events) after ischemic stroke.

Acute Myeloid Leukemia Causes Serious and Partially Irreversible Changes in Secretomes of Bone Marrow Multipotent Mesenchymal Stromal Cells.

In patients with acute myeloid leukemia (AML), malignant cells modify the properties of multipotent mesenchymal stromal cells (MSCs), reducing their ability to maintain normal hematopoiesis. The aim of this work was to elucidate the role of MSCs in supporting leukemia cells and the restoration of normal hematopoiesis by analyzing ex vivo MSC secretomes at the onset of AML and in remission. The study included MSCs obtained from the bone marrow of 13 AML patients and 21 healthy donors. The analysis of proteins contained in the MSCs-conditioned medium demonstrated that secretomes of patient MSCs differed little between the onset of AML and remission; pronounced differences were observed between MSC secretomes of AML patients and healthy donors. The onset of AML was accompanied by a decrease in the secretion of proteins related to ossification, transport, and immune response. In remission, but not at the onset, secretion of proteins responsible for cell adhesion, immune response, and complement was reduced compared to donors. We conclude that AML causes crucial and, to a large extent, irreversible changes in the secretome of bone marrow MSCs ex vivo. In remission, functions of MSCs remain impaired despite the absence of tumor cells and the formation of benign hematopoietic cells.