High Mobility Group Box 1 (HMGB1): Potential Target in Sepsis-Associated Encephalopathy

Abstract

Sepsis-associated encephalopathy (SAE) remains a challenge for intensivists that is exacerbated by lack of an effective diagnostic tool and an unambiguous definition to properly identify SAE patients. Risk factors for SAE development include age, genetic factors as well as pre-existing neuropsychiatric conditions. Sepsis due to certain infection sites/origins might be more prone to encephalopathy development than other cases. Currently, ICU management of SAE is mainly based on non-pharmacological support. Pre-clinical studies have described the role of the alarmin high mobility group box 1 (HMGB1) in the complex pathogenesis of SAE. Although there are limited data available about the role of HMGB1 in neuroinflammation following sepsis, it has been implicated in other neurologic disorders, where its translocation from the nucleus to the extracellular space has been found to trigger neuroinflammatory reactions and disrupt the blood–brain barrier. Negating the inflammatory cascade, by targeting HMGB1, may be a strategy to complement non-pharmacologic interventions directed against encephalopathy. This review describes inflammatory cascades implicating HMGB1 and strategies for its use to mitigate sepsis-induced encephalopathy.

MSC-derived exosomal miR-140-3p improves cognitive dysfunction in sepsis-associated encephalopathy by HMGB1 and S-lactoylglutathione metabolism

“…Eliminating the inflammatory cascade by HMGB1 may be a strategy to complement nonpharmacological interventions targeting SAE 37 . Inflachromene inhibits the expression of HMGB1 and IBA-1 in the hippocampus of CLP mice and restores cognitive function 6 .…”

Salidroside ameliorates acute liver transplantation rejection in rats by inhibiting neutrophil extracellular trap formation

“…Similarly, in vivo experiments demonstrated that salidroside treatment decreases NET production via the HMGB1/TLR4/MAPK signaling pathway, thereby improving hepatic dysfunction, decreasing inflammatory cytokines, and attenuating hepatic histopathological changes. HMGB1, which is a protein that is found in large quantities in chromosomes, acts as a damage-associated molecular pattern that initiates innate inflammatory responses against infection and injury [32]. HMGB1 contributes to the pathogenesis of multiple liver diseases, such as hepatic IRI and acute liver rejection, through TLRs [33].…”

“…HMGB1, which is a protein that is found in large quantities in chromosomes, acts as a damage-associated molecular pattern that initiates innate inflammatory responses against infection and injury [32] . HMGB1 contributes to the pathogenesis of multiple liver diseases, such as hepatic IRI and acute liver rejection, through TLRs [33] .…”

Improved prediction of sepsis-associated encephalopathy in intensive care unit sepsis patients with an innovative nomogram tool

“…In clinical practice, the presence of sepsisassociated delirium is often utilized as a substitute for diagnosing SAE (6), and delirium is evaluated by using a subjective scoring method known as CAM-ICU. Despite the existence of some biomarkers like neurofilament light chains (NFL), S100 calciumbinding protein B (S100β), and neuron-specific enolase (NSE) for predicting the occurrence of SAE (7)(8)(9), these biomarkers are not readily accessible in clinical settings and lack the necessary sensitivity and specificity for accurately predicting SAE. Consequently, new predictive indicators, including clinical parameters, are required to aid in prediction.…”