Relationship between biomarkers of autophagy and inflammation in acute period of ischemic stroke

Abstract

Postischemic neuroinflammation is a critical pathophysiological process within the entire pattern of cerebral ischemia, spanning early injury and tissue repair. According to recent experimental data, autophagy is involved in the regulation of neuroinflammation, influencing the outcome of the acute period of ischemic stroke (IS).Objective. To evaluate the relationship between autophagy biomarkers and inflammation indicators in the dynamics of the acute period of atherothrombotic IS.Materials and methods. 112 patients in the acute period of newly developed atherothrombotic IS and 56 donors (control group) were examined. Patients underwent dynamic clinical and neurological examination on the 1st, 7th and 14th days from the onset of the disease (magnetic resonance imaging, testing using the NIHSS scale, modified Rankin scale). At the same time intervals, blood was drawn for testing. The number of active autophagosomes in peripheral blood was assessed by flow cytometry using a specific Cyto-ID dye. The serum concentrations of proinflammatory cytokines IL‑1β, IL‑8, IL‑18 (interleukins‑1β, -8, -18), TNFα (tumor necrosis factor-α), autophagy biomarkers Beclin‑1, LC 3 and p62 were determined by enzyme-linked immunosorbent assay analysis. C-reactive protein was assessed by a highly sensitive immunoturbidimetric method.Results. A statistically significant increase in the studied parameters was revealed compared to the control group. The maximum increase in inflammation biomarkers was observed on the 1st day, and the maximum increase in key indicators of autophagy (LC 3, Beclin‑1, Cyto-ID) – on the 7th day after the development of ischemia. A direct relationship was established between the level of autophagy and the concentration of inflammatory biomarkers (CRP, IL‑1β, IL‑18, TNF-α) on the 1st and 7th days of acute IS.Conclusions. The identified correlations indicate the participation of activated autophagy in the regulation of post-ischemic neuroinflammation and its involvement in ischemic brain damage in the early stages of the acute period of IS (days 1–7). The results obtained confirm the literature data on the influence of autophagy on the outcome of the acute period of the disease.