Dynamics of the HPA axis and inflammatory cytokines: Insights from mathematical modeling

Malek, Hamed; Ebadzadeh, Mohammad Mehdi; Safabakhsh, Reza; Razavi, Alireza; Zaringhalam, Jalal

doi:10.1016/j.compbiomed.2015.09.018

Cited by 44 publications

(52 citation statements)

References 30 publications

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“…The model fitted the circadian rhythms in cortisol, noradrenaline and TNF-α well; however, the observed ultradian rhythms were omitted (Meyer-Hermann et al 2009). Recently another important work was published by Malek et al (2015), describing the dynamics of the HPA axis and the inflammatory cytokines IL-6 and TNF-α (Malek et al 2015). Malek et al (2015) present a model of five differential equations with two delays, containing 32 parameters and an external periodic function describing the circadian rhythm of the HPA axis.…”

Section: Modeling Backgroundmentioning

confidence: 99%

“…Recently another important work was published by Malek et al (2015), describing the dynamics of the HPA axis and the inflammatory cytokines IL-6 and TNF-α (Malek et al 2015). Malek et al (2015) present a model of five differential equations with two delays, containing 32 parameters and an external periodic function describing the circadian rhythm of the HPA axis. They adopt the HPA axis model from Jelić et al (2005) discussed above.…”

Section: Modeling Backgroundmentioning

confidence: 99%

“…However, this is necessary to obtain sufficient amplitudes of the ultradian rhythms in the simulations. The aim of the work by Malek et al (2015) is to develop a mathematical model describing the interactions between the two subsystems in order to study the bi-directional communication. The model qualitatively captures the data in Clodi et al (2008), but the actual fit could be improved.…”

Section: Modeling Backgroundmentioning

confidence: 99%

“…Inspired by the fundamental idea in the work by Malek et al (2015), we propose a novel integrated model of the acute inflammatory response and the HPA axis. However, we are using a more accurate biological based HPA axis model (Bangsgaard and Ottesen 2016) and an adjusted model of the inflammatory response, inspired by Baker et al Describing the system by nonlinear ordinary differential equations rather than infinite-dimensional delayed differential equations is a novelty compared to the model proposed by Malek et al (2015).…”

Section: Integrated Inflammatory Stress Modelmentioning

confidence: 99%

“…However, we are using a more accurate biological based HPA axis model (Bangsgaard and Ottesen 2016) and an adjusted model of the inflammatory response, inspired by Baker et al Describing the system by nonlinear ordinary differential equations rather than infinite-dimensional delayed differential equations is a novelty compared to the model proposed by Malek et al (2015). Another novelty is the underlying model of the HPA axis, which in this case is able to predict 24-h observations of ACTH and cortisol to a higher degree of precision than the model in Jelić et al (2005) on which the model in Malek et al (2015) is based. Comparing the model to the one in Meyer-Hermann et al (2009), this model is capable of reproducing the observed ultradian oscillations in cortisol.…”

Section: Integrated Inflammatory Stress Modelmentioning

confidence: 99%

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Integrated Inflammatory Stress (ITIS) Model

et al. 2017

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Integrated Inflammatory Stress (ITIS) ModelBangsgaard, Elisabeth O.; Hjorth, Poul G.; Olufsen, Mette S.; Mehlsen, Jesper; Ottesen, Johnny T. Published in: Bulletin of Mathematical BiologyLink to article, DOI: 10.1007/s11538-017-0293-2 Publication date: 2017 Document VersionPublisher's PDF, also known as Version of record Abstract During the last decade, there has been an increasing interest in the coupling between the acute inflammatory response and the Hypothalamic-Pituitary-Adrenal (HPA) axis. The inflammatory response is activated acutely by pathogen-or damagerelated molecular patterns, whereas the HPA axis maintains a long-term level of the stress hormone cortisol which is also anti-inflammatory. A new integrated model of the interaction between these two subsystems of the inflammatory system is proposed and coined the integrated inflammatory stress (ITIS) model. The coupling mechanisms describing the interactions between the subsystems in the ITIS model are formulated based on biological reasoning and its ability to describe clinical data. The ITIS model is calibrated and validated by simulating various scenarios related to endotoxin (LPS) exposure. The model is capable of reproducing human data of tumor necrosis factor alpha, adrenocorticotropic hormone (ACTH) and cortisol and suggests that repeated LPS injections lead to a deficient response. The ITIS model predicts that the most extensive response to an LPS injection in ACTH and cortisol concentrations is observed in the early hours of the day. A constant activation results in elevated levels of the variables in the model while a prolonged change of the oscillations in ACTH and

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Section: Modeling Backgroundmentioning

confidence: 99%

Section: Modeling Backgroundmentioning

confidence: 99%

Section: Modeling Backgroundmentioning

confidence: 99%

Section: Integrated Inflammatory Stress Modelmentioning

confidence: 99%

Section: Integrated Inflammatory Stress Modelmentioning

confidence: 99%

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Integrated Inflammatory Stress (ITIS) Model

et al. 2017

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Baicalin reverse depressive‐like behaviors through regulation SIRT1‐NF‐kB signaling pathway in olfactory bulbectomized rats

Zhang

Guan

2019

Phytotherapy Research

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Depression is a common and detrimental illness that affects up to 120 million people worldwide. The present study was designed to evaluate the antidepressant‐like effects and mechanisms of baicalin on olfactory bulbectomized model of depression. Baicalin treatment (20 and 40 mg/kg) significantly reversed the abnormal levels of sucrose consumption, open field test, and forced swimming test. Treatments with baicalin reversed the olfactory bulbectomized‐induced alterations of serum corticosterone levels to a great extent. Our results further demonstrated that baicalin administration negatively regulated the expression of interleukin (IL)‐1β, IL‐6, and tumor necrosis factor (TNF‐α) in the hippocampus and hypothalamus. Furthermore, baicalin regulated Sirtuin 1 (SIRT1) and decreased the levels of p65 acetylation (ac‐p65) in the hippocampus and hypothalamus. Moreover, in lipopolysaccharides‐induced BV‐2 cells, the levels of inflammatory factors (IL‐1β), p65 acetylation at lysine 310, and SIRT1 expression were different in the group treated with both baicalin and nicotinamide compared with the group treated with baicalin, which suggests that baicalin regulates SIRT1 and thereby inhibits p65 acetylation. In summary, administration of baicalin reduces the levels of pro‐inflammatory cytokines, possibly through regulation of SIRT1‐NF‐kB pathway. Our findings suggest a support into the potential of baicalin in therapeutic effect for depression.

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