Neuroprotective effects of metformin on traumatic brain injury in rats is associated with the AMP-activated protein kinase signaling pathway

Rahimi, Siavash; Ferdowsi, Ahmadreza; Siahposht-Khachaki, Ali

doi:10.1007/s11011-020-00594-3

Cited by 16 publications

(8 citation statements)

References 37 publications

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“…In the db/db mouse model of diabetes, metformin significantly decreased Aβ influx on BBB and neuronal apoptosis and increased intracerebral perfusion of Aβ as well as the expression of the low-density lipoprotein receptor-related protein 1 involved in Aβ efflux [ 93 ]. In rats’ traumatic brain injury (TBI) model, metformin inhibits TBI-mediated secondary injury through AMPK phosphorylation and improves BBB and neurobehavioral function [ 94 ]. Metformin significantly counteracts cigarette smoking-induced downregulation of tight junction protein and loss of BBB integrity by regulating Nrf2 expression [ 95 ].…”

Section: Potential Mechanisms For Actions Of Metformin In the Brainmentioning

confidence: 99%

Actions of Metformin in the Brain: A New Perspective of Metformin Treatments in Related Neurological Disorders

Zhou

Fei

2022

IJMS

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Metformin is a first-line drug for treating type 2 diabetes mellitus (T2DM) and one of the most commonly prescribed drugs in the world. Besides its hypoglycemic effects, metformin also can improve cognitive or mood functions in some T2DM patients; moreover, it has been reported that metformin exerts beneficial effects on many neurological disorders, including major depressive disorder (MDD), Alzheimer’s disease (AD) and Fragile X syndrome (FXS); however, the mechanism underlying metformin in the brain is not fully understood. Neurotransmission between neurons is fundamental for brain functions, and its defects have been implicated in many neurological disorders. Recent studies suggest that metformin appears not only to regulate synaptic transmission or plasticity in pathological conditions but also to regulate the balance of excitation and inhibition (E/I balance) in neural networks. In this review, we focused on and reviewed the roles of metformin in brain functions and related neurological disorders, which would give us a deeper understanding of the actions of metformin in the brain.

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Section: Potential Mechanisms For Actions Of Metformin In the Brainmentioning

confidence: 99%

Actions of Metformin in the Brain: A New Perspective of Metformin Treatments in Related Neurological Disorders

Zhou

Fei

2022

IJMS

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“…However, treatment with AMPK activators could attenuate these behavioral and molecular changes in the pathophysiological profile of metabolic dysfunction (Wang et al 2018 ). Various studies have shown that treatment with metformin is effective in neurological diseases, including high MPTP and increased BDNF (Patil et al 2014 , Lu et al 2016 ), Parkinson’s disease (Choi et al 2010 ; Arbeláez-Quintero and Palacios 2017 ; Lu et al 2020 , Paudel et al 2020 ), epilepsy (H S, Paudel et al 2019 , Demaré et al 2021 ; Sanz et al 2021 , Salvati et al 2022 ), traumatic brain injury (Tao et al 2018 ; Taheri et al 2019 ; Fan et al 2020 ; Rahimi et al 2020 ), neuroprotection of the heart (Zhu et al 2018 , Benjanuwattra et al 2020 , Leech et al 2020 ), and preconditioning in ischemic brain injury (Wang et al 2021a , b , c ). Various studies have shown that BDNF can affect the structure of the anal sphincter (Singh and Rattan 2021 , Singh, Singh et al 2021 ).…”

Section: Metformin and Therapeutic Goalsmentioning

confidence: 99%

The role of AMPK-dependent pathways in cellular and molecular mechanisms of metformin: a new perspective for treatment and prevention of diseases

Hasanvand

2022

Inflammopharmacol

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Metformin can suppress gluconeogenesis and reduce blood sugar by activating adenosine monophosphate-activated protein kinase (AMPK) and inducing small heterodimer partner (SHP) expression in the liver cells. The main mechanism of metformin’s action is related to its activation of the AMPK enzyme and regulation of the energy balance. AMPK is a heterothermic serine/threonine kinase made of a catalytic alpha subunit and two subunits of beta and a gamma regulator. This enzyme can measure the intracellular ratio of AMP/ATP. If this ratio is high, the amino acid threonine 172 available in its alpha chain would be activated by the phosphorylated liver kinase B1 (LKB1), leading to AMPK activation. Several studies have indicated that apart from its significant role in the reduction of blood glucose level, metformin activates the AMPK enzyme that in turn has various efficient impacts on the regulation of various processes, including controlling inflammatory conditions, altering the differentiation pathway of immune and non-immune cell pathways, and the amelioration of various cancers, liver diseases, inflammatory bowel disease (IBD), kidney diseases, neurological disorders, etc. Metformin’s activation of AMPK enables it to control inflammatory conditions, improve oxidative status, regulate the differentiation pathways of various cells, change the pathological process in various diseases, and finally have positive therapeutic effects on them. Due to the activation of AMPK and its role in regulating several subcellular signalling pathways, metformin can be effective in altering the cells’ proliferation and differentiation pathways and eventually in the prevention and treatment of certain diseases. Graphical abstract

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“…In the Syrian hamster model of diabetes, MET completely blocked microvascular leakage [149] . Reductions in oedema were also seen in non-diabetic situations, such as brain and peripheral ischaemia [150] , middle cerebral artery occlusion [151] , traumatic brain injury [152] , glioma-related oedema [153] , cultured pulmonary endothelial monolayers, LPS-induced lung injury, and carrageenan-induced swelling [154] . Clinically, MET reduced cyclic oedema with a remarkable success rate and independently of glycaemic changes [155] .…”

Section: Putative Mechanisms Underlying Met's Protective Effectsmentioning

confidence: 99%

Protection by metformin against severe Covid-19: An in-depth mechanistic analysis

Wiernsperger

Al‐Salameh

Cariou

et al. 2022

Diabetes & Metabolism

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Neuroprotective effects of metformin on traumatic brain injury in rats is associated with the AMP-activated protein kinase signaling pathway

Cited by 16 publications

References 37 publications

Actions of Metformin in the Brain: A New Perspective of Metformin Treatments in Related Neurological Disorders

Actions of Metformin in the Brain: A New Perspective of Metformin Treatments in Related Neurological Disorders

The role of AMPK-dependent pathways in cellular and molecular mechanisms of metformin: a new perspective for treatment and prevention of diseases

Protection by metformin against severe Covid-19: An in-depth mechanistic analysis

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