Post-sepsis cognitive impairment and associated risk factors: A systematic review

Calsavara, Allan Jefferson Cruz; Nobre, Vandack; Barichello, Tatiana; Teixeira, Antônio Lúcio

doi:10.1016/j.aucc.2017.06.001

Cited by 66 publications

(66 citation statements)

References 53 publications

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“…Brain structures including the neuroendocrine system, hippocampus, limbic system, frontal cortex and brainstem of sepsis patients have been found to be damaged [25]. These brain lesions can be associated with psychological disorders (anxiety, depression), long-term cognitive impairment (memory and executive function) and death [26,27]. Studies have reported that patients with sepsis were three times more likely to develop cognitive impairment than patients without sepsis [4].…”

Section: Discussionmentioning

confidence: 99%

Qiang Xin 1 Formula Suppresses Excessive Pro-inflammatory Cytokine Responses and Microglia Activation to Prevent Cognitive Impairment and Emotional Dysfunctions in Experimental Sepsis

Wang

Guo

et al. 2019

Preprint

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Background: Sepsis commonly leads to acute and long-term cognitive and affective impairments which are associated with increased mortality in patients. Neuroinflammation characterized by excessive cytokine release and immune cell activation underlies the behavioral changes associated with sepsis. We previously reported that the administration of a traditional Chinese herbal Qiang Xin 1 (QX1) formula improves survival in septic mice. This study was performed to better understand the effects and the mechanisms of QX1 formula treatment on behavioral changes in septic model. Methods: A preclinical septic model was induced by cecal ligation and puncture in mice. QX1 formula was orally administrated daily. Behavior test including Morris water maze, novel object recognition testing, elevated plus maze and open field testing was performed. Elisa, immunofluorescence, microarray analysis, and Real-time PCR were analyzed. Results: QX1 formula administration significantly improved survival, alleviated overall cognitive impairment and emotional dysfunction in septic mice. QX1 formula administration dramatically inhibited short and long-term excessive pro-inflammatory cytokine production both peripherally and centrally, and was accompanied by diminished microglial activation in septic mice. Biological processes including synaptic transmission, microglia cell activation, cytokine production, microglia cell polarization, as well as inflammatory responses related to signaling pathways including the MAPK signaling pathway and the NF-κB signaling pathway were altered prominently by QX1 formula treatment in the hippocampus of septic mice. In addition, QX1 formula administration decreased the expression of the M1 phenotype microglia gene markers such as Cd32, Socs3, and Cd68, while up-regulated M2 phenotype marker genes including Myc, Arg-1, and Cd206. Conclusions: QX1 formula administration attenuates cognitive deficits, emotional dysfunction, and reduces neuroinflammatory responses to improve survival in septic mice. Diminished microglial activation and altered microglial polarization are involved in the neuroprotective mechanism of QX1 formula.

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Section: Discussionmentioning

confidence: 99%

Qiang Xin 1 Formula Suppresses Excessive Pro-inflammatory Cytokine Responses and Microglia Activation to Prevent Cognitive Impairment and Emotional Dysfunctions in Experimental Sepsis

Wang

Guo

et al. 2019

Preprint

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“…Neuroinflammation plays an important role in pathogenesis of post-sepsis cognitive impairment [1,[8][9][10][11][12][13]. To test the possible mechanism that BHB prevented post-sepsis cognitive impairment, we detected the effects of BHB on neuroinflammation in CLP.…”

Section: Bhb Administration Limited Neuroinflammation and Peripheral mentioning

confidence: 99%

“…Post-sepsis cognitive impairment is one of the major sequelae in sepsis survivors and affects 12.5-21% [1]. To date, aside from the combined use of early and appropriate antimicrobial therapy, restoration of adequate tissue/organ perfusion and timely source control at the early stage of sepsis, no specific method has been available to prevent post-sepsis cognitive impairment [2,3].…”

Section: Introductionmentioning

confidence: 99%

“…Administration of exogenous BHB could reduce reactive oxygen species production via inhibiting HDACs [6] and efficiently protecting neurons in hypoglycemic animals [7]. Interestingly, neuroinflammation and oxidative stress both played important roles in the pathogenesis of post-sepsis cognitive impairment [1,[8][9][10][11][12][13]. Additionally, the level of blood BHB decreases during sepsis [14,15].…”

Section: Introductionmentioning

confidence: 99%

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Subcutaneous administration of β-hydroxybutyrate improves learning and memory of sepsis surviving mice

et al. 2020

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Post-sepsis cognitive impairment is one of the major sequelae in sepsis survivors. Its prevention remains clinically challenging. Here we tested the effects and underlying mechanisms of exogenous β-hydroxybutyrate (BHB) on post-sepsis cognitive impairment. We found that subcutaneous administration of BHB increased survival and body weight recovery of sepsis mice and improved learning and memory of sepsis surviving mice in a cecal ligation and perforation-induced sepsis model. Additionally, the improvement of learning and memory of sepsis surviving mice was still detected even if BHB was administrated at the late stage of sepsis. In contrast, glucose solution did not show similar effects. Mechanistically, subcutaneous administration of BHB increased the BHB level of hippocampus, and limited neuroinflammation and neuroplasticity damage in sepsis mice. Intracerebroventricular administration of BHB also alleviated neuroinflammation and cognitive impairment of sepsis surviving mice. In the coculture of neurons, astrocytes, and BV2 cells (a microglial cell line), knocking down the expression of microglial HCA2 (BHB receptor) via a specific shRNA reduced the protection of BHB to lipopolysaccharide-induced inflammatory response and neuron damage more significantly than knocking down neuronal MCT2 (BHB transporter). These data showed that (1) BHB was a potential pharmacological adjunct treatment for prevention of post-sepsis cognitive impairment and (2) inhibiting neuroinflammation via HCA2 was an important mechanism.

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“…Long‐term cognitive impairment after critical illness is defined as the neuropsychological changes that tend to persist and cause deficits of a magnitude that impair daily function . The incidence of cognitive impairment after sepsis has been reported to range from 4% to 62% . Both physical and cognitive impairment after intensive care are likely modifiable outcomes as well as being outcomes reported as important to patients who survived acute respiratory failure …”

Section: Introductionmentioning

confidence: 99%

Long‐term patient‐important outcomes after septic shock: A protocol for 1‐year follow‐up of the CLASSIC trial

Kjær

Meyhoff

Madsen

et al. 2019

Acta Anaesthesiol Scand

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Background In patients with septic shock, mortality is high, and survivors experience long‐term physical, mental and social impairments. The ongoing Conservative vs Liberal Approach to fluid therapy of Septic Shock in Intensive Care (CLASSIC) trial assesses the benefits and harms of a restrictive vs standard‐care intravenous (IV) fluid therapy. The hypothesis is that IV fluid restriction improves patient‐important long‐term outcomes. Aim To assess the predefined patient‐important long‐term outcomes in patients randomised into the CLASSIC trial. Methods In this pre‐planned follow‐up study of the CLASSIC trial, we will assess all‐cause mortality, health‐related quality of life (HRQoL) and cognitive function 1 year after randomisation in the two intervention groups. The 1‐year mortality will be collected from electronic patient records or central national registries in most participating countries. We will contact survivors and assess EuroQol 5‐Dimension, ‐5‐Level (EQ‐5D‐5L) and EuroQol‐Visual Analogue Scale and Montreal Cognitive Assessment 5‐minute protocol score. We will analyse mortality by logistic regression and use general linear models to assess HRQoL and cognitive function. Discussion With this pre‐planned follow‐up study of the CLASSIC trial, we will provide patient‐important data on long‐term survival, HRQoL and cognitive function of restrictive vs standard‐care IV fluid therapy in patients with septic shock.

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Post-sepsis cognitive impairment and associated risk factors: A systematic review

Cited by 66 publications

References 53 publications

Qiang Xin 1 Formula Suppresses Excessive Pro-inflammatory Cytokine Responses and Microglia Activation to Prevent Cognitive Impairment and Emotional Dysfunctions in Experimental Sepsis

Qiang Xin 1 Formula Suppresses Excessive Pro-inflammatory Cytokine Responses and Microglia Activation to Prevent Cognitive Impairment and Emotional Dysfunctions in Experimental Sepsis

Subcutaneous administration of β-hydroxybutyrate improves learning and memory of sepsis surviving mice

Long‐term patient‐important outcomes after septic shock: A protocol for 1‐year follow‐up of the CLASSIC trial

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