DOI: https://doi.org/10.22141/1608-1706.4.20.2019.178750

Stage of endogenous intoxication syndrome in experimental brain injury

S.V. Ziablytsev, V.M. Elskyy

Abstract


Background. This study deals with the results of the analysis of longstanding work carried out under the direction of the Corresponding Member of the National Academy of Medical Sciences of Ukraine, prof. V.М. Elskyy, Head of the Pathophysiology Department of M. Gorky Donetsk National Medical University, on experimental reproduction and analysis of endogenous intoxication syndrome (EIS) in the brain injury. This work aimed to develop a conception of staging and key mechanisms for the development of EIS associated with brain injury. Materials and methods. The study was conducted on 555 white, non-breeding male rats Wistar; experimental brain injury was reproduced by the method of V.M. Yelskyy, S.V. Ziablitsev (2005). In blood, the dynamics of 30 indicators of hormones, metabolites, immunological and other biologically active substances was determined; 7 indicators of activity of enzymes and additionally counted 5 indices (in general in this study 42 indicators were studied). Disorders of the central nervous system function were evaluated according to the method of assessing the neurological deficiency (scores) by the indicators of the level of consciousness, the state of the reflex field, hearing, muscle tone of the body and extremities, reaction to light and pain, respiration, movement and some behavioral reactions. The morphological parameters of brain damage were also determined. Results. The analysis of the studied parameters dynamics and their relationships allowed distinguishing four stages of EIS development: reactive-metabolic, inflammatory-toxic, the stage of systemic endogenous intoxication (the final development of EIS) and the stage of development of multiple organ failure (MOF). The reactive-metabolic stage was characterized by hyperergic reaction of neuroendocrine systems with catabolic action; hyperglycemia, hyperinsulinemia and insulin resistance; hypermetabolism. The severe hyperenzymemia, indicating damage to the cell membranes and lysosomal membranes, manifestations of endogenous intoxication (accumulation in the blood of molecules of medium mass and products of lipoperoxidation), generalized inflammatory reactions (increased inflammatory blood mediators, including IL-1β, TNF-α, IL-6) are typical for the inflammatory-toxic stage. The stage of systemic endogenous intoxication is characterized by a sharp accumulation of lactate in blood, indicating the systemic hypoxia inclusion; a sharp secondary increase in the molecules of medium mass with the accumulation of low molecular weight and aromatic peptides; a sharp secondary increase in proinflammatory cytokines; activation of MMP-9 and TIMP-1; a sharp increase in neuronal proteins S100B and NSE, indicating the progression of brain damage. Stage of MOF development is characterized by the accumulation in the blood of urea and creatinine, damage to red blood cells, myocardium; a sharp increase in NSE; the appearance in the blood of large quantities of antiphospholipid antibodies, which reflected the inclusion of autoimmune processes. Conclusions. The obtained data allowed developing a concept for the development of EIS in brain injury and to identify the key components of its pathogenesis, which can be used to develop appropriate measures of pathogenetic treatment.

Keywords


brain injury; endogenous intoxication syndrome; multiple organ failure

References


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