Abstract
Sepsis is not only a significant cause of mortality worldwide but has particularly devastating effects on the central nervous system of survivors. It is therefore crucial to understand the molecular structure, physiology, and events involved in the pathogenesis of sepsis-associated encephalopathy, so that potential therapeutic advances can be achieved. A key determinant to the development of this type of encephalopathy is morphological and functional modification of the blood–brain barrier (BBB), whose function is to protect the CNS from pathogens and toxic threats. Key mediators of pathologic sequelae of sepsis in the brain include cytokines, including TNF-α, and sphingolipids, which are biologically active components of cellular membranes that possess diverse functions. Emerging data demonstrated an essential role for sphingolipids in the pulmonary vascular endothelium. This raises the question of whether endothelial stability in other organs systems such as the CNS may also be mediated by sphingolipids and their receptors. In this review, we will model the structure and vulnerability of the BBB and hypothesize mechanisms for therapeutic stabilization and repair following a confrontation with sepsis-induced inflammation.
Highlights
AND OVERVIEWSepsis is a leading cause of morbidity and mortality worldwide
With the exclusion of drug-induced and other metabolic etiologies, this syndrome is termed “sepsis-associated encephalopathy (SAE)” and is the most common form of encephalopathy occurring in critical care settings [4,5,6,7]
While MRI may be negative in confirmed SAE, EEG abnormalities may be present even preceding the onset of symptoms in 50% of cases
Summary
Sepsis is a leading cause of morbidity and mortality worldwide. In 2016, consensus guidelines honed the definition of sepsis to refer to “life threatening organ dysfunction caused by a dysregulated host response to infection” [1]. Involvement of the CNS results in sepsis-induced brain dysfunction, which is manifested clinically by a neuropsychiatric continuum starting in an acute confusional state and coma [2, 3]. SAE is widely understood as the presence of diffuse cerebral dysfunction in the presence of sepsis but in the absence of CNS infection and other forms of encephalopathy [9, 10]. It is usually manifested by disturbances of the sleep–wake cycle, impaired consciousness, mild cognitive dysfunction, overt delirium, and coma [4]
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