Regional-specific activation of phagocytosis in the rat brain in the conditions of sepsis-associated encephalopathy
DOI:
https://doi.org/10.14739/2310-1210.2021.1.224921Keywords:
sepsis-associated encephalopathy, phagocytosis, microglia, CD68, transmission microscopy electionAbstract
In the condition of sepsis-associated encephalopathy (SAE), the brain neuroinflammatory response is considered as one of the most critical mechanisms of tissue damage and impaired cerebral homeostasis. The main cell population of the brain responsible for the immune surveillance is microglia, and its phagocytic activity is a fundamental function providing both homeostatic and damaging properties.
The aim of this study was to determine the immunohistochemical and ultrastructural specificity of the phagocytosis activation in different rat brain regions in the conditions of experimental sepsis.
Materials and methods. The study was conducted in Wistar rats: 5 sham-operated animals and 20 rats with cecum ligation and puncture (CLP). The immunohistochemical study of CD68 expression in the cortex, white matter, hippocampus, thalamus, caudate/putamen was carried out in the period of 20–48 h postoperatively. The cerebral cortex was examined using transmission electron microscopy.
Results. Beginning from the 20th h after CLP, there was a significant dynamic increase in the values of the relative area of CD68 expression, the number of immunopositive cells, as well as the percentage of immunopositive cells with amoeboid morphology in all animals of the CLP group, with a predominance of the indicators in the lethal group of rats. The highest levels of phagocytic activity were noted in the white matter and caudate/putamen in both the survived and non-survived animals. Ultrastructurally, the microgliocytes of the lethal group were characterized by signs of actively phagocytic cells and extensive glial-neuronal interaction; phagocytosing microglia in the survived animals showed an active involvement in the processes of necrotic debris elimination into the vasculature.
Conclusions. In the conditions of SAE, there is the early and dynamic increase in phagocytosis activation with the predominant localization in the brain white matter and caudate/putamen, which could conceivably indicate a special role of these brain areas in the mechanisms of neuroinflammatory response in the conditions of systemic inflammation. In the brain of non-survived animals, the phagocytosis indices are higher than in the group of survivors, which most likely indicates a natural response of microglia to more pronounced destructive processes, but it does not preclude a concurrent neurotoxic activity of CD68-positive cells on the surrounding tissue elements.
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