Emodin Promotes Autophagy and Prevents Apoptosis in Sepsis-Associated Encephalopathy through Activating BDNF/TrkB Signaling

Background: Studies have demonstrated an important impact of systemic inflammation in the central nervous system, which could be related to psychiatric disorders’ pathophysiology. Ketamine can have anti-inflammatory proprieties, but dose-dependently effects need to be studied. Objective: To evaluate the effect of different doses of ketamine on levels of neurotrophins and inflammatory cytokines in the brains of rats. Methods: Wistar rats were submitted to the cecal ligation and puncture (CLP) model of sepsis. Thirty days after the CLP procedure, the rats received an intraperitoneal injection (i.p.) of ketamine (5, 15, or 25 mg/kg) or saline, once a day for seven days. The rats were killed 30 minutes after the last i.p. injection. The frontal cortex, hippocampus, and striatum were dissected for analysis of IL-1𝛽, IL-6, IL-10, TNF-α, BDNF, NGF, NT-3, and GDNF levels. Results: CLP increased the levels of IL-1𝛽, IL-6, IL-10, and TNF-α levels in the frontal cortex and/or hippocampus of rats. Besides, BDNF levels were decreased by CLP in all structures analyzed. NGF and GDNF were decreased only in the hippocampus. Ketamine at 5 mg/kg reversed all alterations caused by CLP and per se increased the levels of BDNF and NGF in the frontal cortex and/or hippocampus. Ketamine at 15 mg/kg increased BDNF and NGF levels. In turn, Ketamine at 25mg/kg potentiates the inflammatory injury on the brain induced by CLP. Conclusion:We suggest that ketamine could work differently in a systemic inflammation environment, and caution needs to be taken depending on the inflammatory history of the patient.

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“…The decrease in hippocampal BDNF levels caused by CLP is congruent with previous studies [6,36,37] .…”

Section: Discussionsupporting

confidence: 92%

Bimodal effect of ketamine on neurotrophic factors and inflammatory parameters in cecal ligation and puncture-induced sepsis model

Valvassori

Réus

Mastella

et al. 2022

Preprint

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“…Both of these compounds can mediate brain-derived neurotrophic factor (BDNF) expression. 31 , 32 In addition to their positive effects on cognitive function and long-term memory, serum BDNF level has been implicated not only in neuroinflammation but also in inflammatory processes in visceral organs, especially in RA. 33 Meanwhile, BDNF, together with its high-affinity tyrosine kinase type B (TrKB) receptor, has been linked to the onset of severe female reproductive disorders, including endometriosis.…”

Section: Discussionmentioning

confidence: 99%

The Prescription of Chinese Herbal Medicine and Risk of Endometriosis in Women with Rheumatoid Arthritis: A Population-Based Cohort Study

Chen¹,

Livneh²,

Chen³

et al. 2022

IJWH

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Purpose The systemic inflammation is believed to provide an outline of the association between rheumatoid arthritis (RA) and endometriosis. This retrospective cohort study aimed to explore the association of Chinese herbal medicine (CHM) use with the prevention of endometriosis onset in women diagnosed with RA. Methods We utilized the claims data from the National Health Insurance of Taiwan from 2000 to 2009 and excluded individuals diagnosed with endometriosis before being diagnosed with RA, using age at clinical diagnosis. After selection and propensity-score matching, a total of 5992 females aged ≧20 years old and with newly diagnosed RA but without endometriosis at baseline were included, which contained 2996 CHM users and 2996 non-CHM users. All of them were followed until the end of 2013 to measure the incidence of endometriosis. Results During the study period, we noticed that CHM users had a substantially lower incidence of endometriosis compared to non-CHM users (2.54 vs 5.19 per 1000 person-years). Use of CHM correlated significantly with a lower endometriosis likelihood even after adjusting for potential covariates, with the adjusted hazard ratio of 0.47 (95% confidence interval, 0.35–0.65). A longer duration of CHM use was associated with a reduction in endometriosis risk, especially in those using CHM for more than 730 days. Uses of several herbal products may be associated with a lower risk of endometriosis, like Ge-Gen, Da-Huang, Huang-Qin, Ye-Jiao-Teng, Chuan-Niu-Xi, Shu-Jing-Huo-Xue-Tang, Du-Huo-Ji-Sheng-Tang, Ge-Gen-Tang, Shao-Yao-Gan-Cao-Tang, Ping-Wei-San, Gan-Lu-Yin, and Dang-Gui-Nian-Tong-Tang. Conclusion Taken together, adding CHM to conventional therapy may reduce the incidence of endometriosis in women with RA. The therapeutic mechanisms and safety of these natural products may be a direction for future clinical studies.

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“…sepsis-associated encephalopathy after CLP, induction of autophagy in hippocampal neurons or mitophagy in cerebral microvascular endothelial cells reduced inflammation and pathological injury and ameliorated cognitive dysfunction [60,61].…”

Section: Key Pointsmentioning

confidence: 96%

Nutrition and autophagy deficiency in critical illness

Vanhorebeek

Casaer

Gunst

2023

Current Opinion in Critical Care

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Purpose of review Critical illness imposes a severe insult on the body, with various stressors triggering pronounced cell damage. This compromises cellular function, leading to a high risk of multiple organ failure. Autophagy can remove damaged molecules and organelles but appears insufficiently activated during critical illness. This review discusses insight into the role of autophagy in critical illness and the involvement of artificial feeding in insufficient autophagy activation in critical illness. Recent findings Animal studies manipulating autophagy have shown its protective effects against kidney, lung, liver, and intestinal injury after several critical insults. Autophagy activation also protected peripheral, respiratory, and cardiac muscle function, despite aggravated muscle atrophy. Its role in acute brain injury is more equivocal. Animal and patient studies showed that artificial feeding suppressed autophagy activation in critical illness, particularly with high protein/amino acid doses. Feeding-suppressed autophagy may explain short and long-term harm by early enhanced calorie/protein feeding in large randomized controlled trials. Summary Insufficient autophagy during critical illness is at least partly explained by feeding-induced suppression. This may explain why early enhanced nutrition failed to benefit critically ill patients or even induced harm. Safe, specific activation of autophagy avoiding prolonged starvation opens perspectives for improving outcomes of critical illness.

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Emodin Promotes Autophagy and Prevents Apoptosis in Sepsis-Associated Encephalopathy through Activating BDNF/TrkB Signaling

Cited by 33 publications

References 45 publications

Bimodal effect of ketamine on neurotrophic factors and inflammatory parameters in cecal ligation and puncture-induced sepsis model

Bimodal effect of ketamine on neurotrophic factors and inflammatory parameters in cecal ligation and puncture-induced sepsis model

The Prescription of Chinese Herbal Medicine and Risk of Endometriosis in Women with Rheumatoid Arthritis: A Population-Based Cohort Study

Nutrition and autophagy deficiency in critical illness

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