Sepsis-associated encephalopathy (SAE) is a common complication of sepsis, referring to a diffuse brain dysfunction caused by sepsis in the absence of direct central nervous system (CNS) infection. SAE occurs in up to 70% of patients with sepsis. Globally, the annual incidence of sepsis ranges from 30.0 to 48.9 million cases, resulting in approximately 11 million deaths per year, which accounts for 20% of all global mortalities. SAE is identified as an independent risk factor contributing to the increased mortality rate among these patients. Early diagnosis of SAE and related cerebral protection interventions hold significant clinical importance. Currently, the main indicators of brain function for sepsis patients include Glasgow coma score (GCS), confusion assessment method for the intensive care unit (CAM-ICU), electroencephalogram (EEG), brain CT or magnetic resonance imaging (MRI) and other related imaging changes, which have the problems of low sensitivity, poor specificity, and non-objective evaluation of the results of the diagnosis of SAE. This article focuses on the latest progress in the pathogenesis of SAE and systematically reviews potential biomarkers related to the onset of SAE from multiple aspects, including inflammatory markers, endothelial and neuronal injury markers, and metabolic markers. This will provide new insights for the clinical diagnosis and treatment of SAE.
Humans ; Sepsis-Associated Encephalopathy/therapy* ; Biomarkers ; Sepsis/complications* ; Magnetic Resonance Imaging ; Electroencephalography ; Brain Diseases/etiology*

OBJECTIVETo observe the efficacy of Xingnaojing Injection (XI) in treatment of sepsis-associated encephalopathy (SAE).

METHODSTotally 65 SAE patients were retrospectively analyzed at EICU from September 2010 to September 2013. They were assigned to the control group (32 cases) and the treatment group (33 cases) according to whether they received XI. Patients in the control group received anti-infection and symptomatic support, while those in the treatment group were intravenously injected with XI at 20 mL per day for additional 7-10 days. The fever clearance time, Glasgow coma scale (GCS), C-reactive protein (CRP), neuron-specific enolase (NSE), and improvement of electroen-cephalogram (EEG) were observed in the two groups.

RESULTSCompared with the control group, the fever clearance time was shortened, CRP levels decreased, GCS score and efficacy of EEG was alleviated in the treatment group after treatment with statistical difference (P < 0.05). No adverse reaction occurred during medication.

CONCLUSIONX1 was safe and effective in treatment of SAE.

C-Reactive Protein ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; therapeutic use ; Humans ; Injections ; Phosphopyruvate Hydratase ; metabolism ; Sepsis-Associated Encephalopathy ; drug therapy ; Treatment Outcome

BACKGROUNDBrain dysfunction is a frequent complication of sepsis, usually defined as sepsis-associated encephalopathy (SAE). Although the Notch signaling pathway has been proven to be involved in both ischemia and neuronal proliferation, its role in SAE is still unknown. Here, the effect of the Notch signaling pathway involved γ-secretase inhibitor DAPT on SAE in septic rats was investigated in a cecal ligation and puncture (CLP) model.

METHODSFifty-nine Sprague-Dawley rats were randomly divided into four groups, with the septic group receiving the CLP operation. Twenty-four hours after CLP or sham treatment, rats were sacrificed and their hippocampus was harvested for Western blot analysis. TNF-α expression was determined using an enzyme-linked immunosorbent assay (ELISA) kit. Neuronal apoptosis was assessed by TUNEL staining, and neuronal cell death was detected by H&E staining. Finally, a novel object recognition experiment was used to evaluate memory impairment.

RESULTSOur data showed that sepsis can increase the expression of hippocampal Notch receptor intracellular domain (NICD) and poly (adenosine diphosphate [ADP]-ribose) polymerase-1 (PARP-1), as well as the inflammatory response, neuronal apoptosis, neuronal death, and memory dysfunction in rats. The γ-secretase inhibitor N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine t-butyl ester (DAPT) can significantly decrease the level of NICD and PARP-1, reduce hippocampal neuronal apoptosis and death, attenuate TNF-α release and rescue cognitive impairment caused by CLP.

CONCLUSIONThe neuroprotective effect of DAPT on neuronal death and memory impairment in septic rats, which could be a new therapeutic approach for treating SAE in the future.

Amyloid Precursor Protein Secretases ; antagonists & inhibitors ; Animals ; Apoptosis ; drug effects ; Dipeptides ; therapeutic use ; Hippocampus ; drug effects ; metabolism ; Male ; Neurons ; cytology ; drug effects ; Neuroprotective Agents ; Poly (ADP-Ribose) Polymerase-1 ; Poly(ADP-ribose) Polymerases ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Notch ; metabolism ; Sepsis ; complications ; Sepsis-Associated Encephalopathy ; drug therapy ; enzymology ; Signal Transduction ; drug effects