Pathomorphological parameters of sepsis-associated encephalopathy in deceased septic patients without purulent lesions to the brain

Abstract

Sepsis-associated encephalopathy (SAE) clinically manifests by delirium and decreased consciousness less than 15 points on Glasgow Coma Scale. SAE pathophysiology includes neuroinflammation, ischemic-hypoxic and dysmetabolic mechanisms. Despite the high frequency and the important role in thanatogenesis, pathomorphological criteria of SAE remain to be defined. The aim of the study was to specify the key pathomorphological parameters of sepsis-associated encephalopathy in deceased septic patients without purulent lesions to the brain by defining the changes of neurogliovascular unit and the level of tissue ammonia. Material and methods. Using pathohistological, histochemical, and immunohistochemical methods we studied cerebral cortex and white matter, hippocampus, thalamus, and cerebellum of 35 deceased septic patients with SAE in comparison with the control group, which included 30 patients who died from acute cardiovascular failure without CNS pathology. Results. In SAE, small foci of encephalolysis due to thrombosis of microvessels, ischemic-hypoxic and apoptotic changes in neurons are associated with the following parameters that are reliably (p < 0.05) different from the control group: higher (up to 199.48 %) level of tissue ammonia and increased number (up to 316.07 %) of caspase-3+ apoptotic neurons in the cortex, hippocampus, thalamus, and cerebellum; in all studied brain regions, an increased expression level of astrocytic glial fibrillary acidic protein (up to 192.69 %), glutamine synthetase (up to 134.41 %) and aquaporin-4 (up to 400.8 %); significant (up to 947.01 %) expansion of perivascular and pericellular “edematous” spaces, increased (up to 479.58 %) immunopositive area of extravascular CD68+ microgliocytes and increased (up to 374.43 %) proportion of CD68+ ameboid microgliocytes, increased (up to 3.66 times) number of Alzheimer type 2 astrocytes in cerebral cortex, thalamus, and cerebellum; increased (up to 2 times) number of amyloid bodies in the thalamus and cerebellum. Conclusions. The obtained data indicate that the delirious state, loss of consciousness and other manifestations of SAE are associated with ischemic-hypoxic and ammonia-induced ischemic and apoptotic changes of the brain neurones; small foci of encephalolysis; adaptive remodeling and dystrophic changes of astrocytes; microglial reactiveness with increased proportion of phagocytic microgliocytes; brain edema and dysfunctional glymphatics.