Metformin ameliorates the status epilepticus- induced hippocampal pathology through possible mTOR modulation

Bojja, Sree Lalitha; Medhi, Bikash; Anand, Shashi; Bhatia, Alka; Joshi, Rupa; Minz, Ranjana Walker

doi:10.1007/s10787-020-00782-8

Cited by 17 publications

(7 citation statements)

References 73 publications

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“…In particular, activation of AMPK by metformin inhibits mTOR signaling and has resulted in improved seizure control in models of mTOR overactivation [1,3,61,62]. These results were confirmed by a recent report indicating that AMPK activation by metformin improved lithium-and pilocarpine-induced status epilepticus in rats by inhibiting the mTOR pathway [63]. The beneficial effect of AMPK activation by metformin and calorie restriction on the main symptoms of an electric-ignition model of epilepsy, especially those related to generalized seizures, has also been observed [64].…”

Section: Epilepsysupporting

confidence: 72%

Beneficial Effects of Metformin on the Central Nervous System, with a Focus on Epilepsy and Lafora Disease

Sanz

Serratosa

Sánchez

2021

IJMS

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Metformin is a drug in the family of biguanide compounds that is widely used in the treatment of type 2 diabetes (T2D). Interestingly, the therapeutic potential of metformin expands its prescribed use as an anti-diabetic drug. In this sense, it has been described that metformin administration has beneficial effects on different neurological conditions. In this work, we review the beneficial effects of this drug as a neuroprotective agent in different neurological diseases, with a special focus on epileptic disorders and Lafora disease, a particular type of progressive myoclonus epilepsy. In addition, we review the different proposed mechanisms of action of metformin to understand its function at the neurological level.

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Section: Epilepsysupporting

confidence: 72%

Beneficial Effects of Metformin on the Central Nervous System, with a Focus on Epilepsy and Lafora Disease

Sanz

Serratosa

Sánchez

2021

IJMS

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“…Support for the hypothesis that inflammation contributes to ictogenesis comes from rodent models of pilocarpineinduced, kainic acid-induced, and pentylenetetrazoleinduced seizure propensities that include a robust inflammatory response. [64][65][66][67][68][69][70] Anti-inflammatory approaches involving inhibition of prostaglandin EP2 receptors, 65,66 inhibition of mTOR signaling, 64 and inhibition of neurotensin receptor 2 reduce the inflammation-associated phenomena (including seizure occurrence) attributed to pilocarpine, and thus offer support for the hope that these anti-inflammatory approaches might reduce seizure occurrence in humans.…”

Section: Non-inflammatory Stimuli That Induce Inflammation-related Ep...mentioning

confidence: 99%

Systemic inflammation as a biomarker of seizure propensity and a target for treatment to reduce seizure propensity

et al. 2023

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People with diabetes can wear a device that measures blood glucose and delivers just the amount of insulin needed to return the glucose level to within bounds.Currently, people with epilepsy do not have access to an equivalent wearable device that measures a systemic indicator of an impending seizure and delivers a rapidly acting medication or other intervention (e.g., an electrical stimulus) to terminate or prevent a seizure. Given that seizure susceptibility is reliably increased in systemic inflammatory states, we propose a novel closed-loop device where release of a fast-acting therapy is governed by sensors that quantify the magnitude of systemic inflammation. Here, we review the evidence that patients with epilepsy have raised levels of systemic indicators of inflammation than controls, and that some anti-inflammatory drugs have reduced seizure occurrence in animals and humans. We then consider the options of what might be incorporated into a responsive anti-seizure system.

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“…In human neural stem cells, metformin inhibited advanced glycosylation end product-induced inflammation and rescued the transcript and protein expression levels of ACC and IKK [ 150 ]. Metformin decreased glial activation induced by status epilepticus, downregulated mRNA levels of proinflammatory cytokines and chemokines, and improved BBB permeability and hippocampal neuron density, partly mediated by the mTOR pathway [ 151 ]. Metformin inhibits microglial activation in general, and immune reactivity of proinflammatory marker and anti-inflammatory marker [ 65 ].…”

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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Metformin ameliorates the status epilepticus- induced hippocampal pathology through possible mTOR modulation

Cited by 17 publications

References 73 publications

Beneficial Effects of Metformin on the Central Nervous System, with a Focus on Epilepsy and Lafora Disease

Beneficial Effects of Metformin on the Central Nervous System, with a Focus on Epilepsy and Lafora Disease

Systemic inflammation as a biomarker of seizure propensity and a target for treatment to reduce seizure propensity

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

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