engleski

Histological aspects of oxidative stress in septic encephalopathy

Septic encephalopathy is considered as systemic response to infection, since no single type of microorganism was associated with development of neurological abnormalities. Neurological impairment can range from delirium or acute confusion to coma, seizures and focal changes. In available studies of brain histology observed histological changes range from absence of identifiable morphological lesions to severe brain edema, formation of micro abscesses, hemorrhage-like vascular lesions, watershed infarcts and numerous protoplasmic astrocytes and microglia in protracted severe sepsis. Thus, in septic encephalopathy mechanisms of brain dysfunction are numerous and probably interrelated. including multiple brain microabscesses and effects of bacterial toxins on the brain macrophage system, which induces inflammatory reaction, brain edema and reduced cerebral blood flow. This network of reactions includes cytokines, neutrophils and release of cytotoxic reactive oxygen species (ROS) together with proteinases. The other source of ROS in septic shock can be ischemia– reperfusion injury as a result of intermittent hypotension in septic patients, or hemorrhage and thrombotic complication as result of disturbance in coagulation. ROS are important effector molecules in the inflammatory and antimicrobial activity. ROS also induce lipid peroxidation in cellular membrane and circulating lipoproteins, generating toxic aldehydes, the end products of lipid peroxidation . Highly reactive aldehyde, 4-hydroxynonenal (HNE) is one of the most important products of polyunsaturated fatty acids (PUFA) peroxidation. HNE might be one of major mediators of oxidative stress in different pathological conditions in brain and usually acts like ” second toxic messenger” of lipid peroxidation in blood, brain-blood barrier and in brain tissue. Monoclonal antibodies have been developed against HNE-histidine conjugate that allow morphological analysis of the tissue distribution of aldehyde. In our autopsy study of 12 cases who died during severe septic encephalopaty, we observed that in most cases histological changes range from absence of identifiable morphological lesions, severe brain edema and “ red neurons” , to watershed infarcts and rare acute brain microabscesses and microglial accumulation around blood vessels. Immunohistochemical reaction to HNE was strong in perivascular brain edema fluid and arachnoidea, in hemolytic content of blood vessels and blood vessels’ wall, particularly in subarachnoidal space. Swelling of astrocytes was associated with the presence of HNE. The strongest HNE reaction was present in neurons of watershed region and midbrain. Strong HNE-positivity in the blood vessels content, blood vessels walls and astrocytes at the blood-brain barrier indicates a humoral origin of the HNE adducts and an altered function of the blood-brain barrier under the septic condition.

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