Immunohistochemical study of the brain glutamine synthetase expression in the rat septic model
DOI:
https://doi.org/10.14739/2310-1237.2022.1.251248Keywords:
sepsis-associated encephalopathy, astroglial reactivity, GSAbstract
Severe sepsis is accompanied by multiple organ dysfunction where acute liver failure (ALF) plays one of the most critical roles. The principal sign of acute hepatic encephalopathy accompanying ALF is ammonia induced edema of astrocytes. In case of ALF in sepsis, one can suppose increase in systemic and brain ammonia. Astroglia are target cells for ammonia metabolism as they are principal source of glutamine-synthetase (GS). Previous studies have reported that ALF stimulates increase in astroglial GS which correlates with deterioration of the animal state.
The aim of the study was to determine the level of glutamine synthetase expression in different brain regions of rats in the conditions of experimental sepsis.
Materials and methods. The study was conducted in Wistar rats: 5 sham-operated (control) animals and 20 rats with cecum ligation and puncture (CLP) septic model. Immunohistochemical study of GS expression was performed in the cortex, white matter, hippocampus, thalamus, caudate nucleus/putamen in the period of 20–48 h after CLP.
Results. Starting at 12th h after CLP, operated animals displayed progressive impairment finished by profound lethargy and respiratory failure. Between 20–38 h, 9 animals expressed final mentioned symptoms and were euthanized (CLP-B, non-survived), 11 rats displayed less expressed suffering up to 48 h (CLP-A, survived). At 23 h in CLP-B and 48 h in CLP-A rats, liver tissue displayed morphological signs of the focal irreversible damage which was aggravated with time after CLP which could be observed dynamically in non-survived group. Both CLP-A and CLP-B rats showed gradual elevation of GS in all studied brain regions. From 24 to 38 h after CLP, non-survived animals showed significant region-specific dynamic increase in GS expression: in the cortex – by 69.35 %, hippocampus – by 53.6 %, thalamus – by 50.0 %; with the most substantive elevation in the cortex – 1.69-fold increase compared to control.
Conclusions. In CLP model, 24 h after operation there is significant dynamic increase in GS level in the cortical, hippocampal and thalamic regions of the rat brain with the most prominent in the cortex. Heterogeneous increase in GS indicates regions more or less vulnerable for incoming systemic agents as well as region-specific reactiveness of the brain tissue, including local astroglia, to these factors in septic conditions. Morphological signs of sepsis-associated liver damage preceding significant increase in the brain GS by 1 h, might suppose addition of the liver failure to the course of sepsis which is accompanied by increased level of hepatogenic toxins (presumably including ammonia) in the blood and in the brain parenchyma by 23 h after CLP. The latter might propose an active implication of hepatogenic detrimental agents in sepsis pathophysiology and involvement of reactively increased brain GS levels in the complex mechanisms of sepsis-associated encephalopathy.
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