Repetitive Transcranial Magnetic Stimulation Improves Neuropathy and Oxidative Stress Levels in Rats with Experimental Cerebral Infarction through the Nrf2 Signaling Pathway

Liang, Hui; Xu, Chi; Hu, Shijun; Wu, Gang; Lin, Jie; Liu, Tao; Xu, Jingtao

doi:10.1155/2021/3908677

Cited by 14 publications

(17 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Improvement in oxidative status following iTBS, and its antioxidative potential ( Medina-Fernández et al, 2018 ; Stevanovic et al, 2020 ) could be mediated via nuclear factor (erythroid-derived 2)-like 2 (Nrf2) that is involved in transcriptional regulation of antioxidative enzymes ( Jaiswal, 2004 ). Previous studies reported that TMS increases the expression of Nrf2 in neuroinflammatory conditions ( Tasset et al, 2013 ; Liang et al, 2021 ), which could also be the mechanism in TMT-mediated oxidative stress. To dissect molecular changes that could underlie favorable effects of iTBS, we investigated PI3K/Akt/mTOR and ERK 1/2 signaling as key players in the regulation of several processes, including proliferation, apoptosis, learning, and memory ( Xu et al, 2020 ).…”

Section: Discussionmentioning

confidence: 94%

Intermittent Theta Burst Stimulation Ameliorates Cognitive Deficit and Attenuates Neuroinflammation via PI3K/Akt/mTOR Signaling Pathway in Alzheimer’s-Like Disease Model

Stekic

Zeljković

Kontic

et al. 2022

Front. Aging Neurosci.

View full text Add to dashboard Cite

Neurodegeneration implies progressive neuronal loss and neuroinflammation further contributing to pathology progression. It is a feature of many neurological disorders, most common being Alzheimer’s disease (AD). Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive stimulation which modulates excitability of stimulated brain areas through magnetic pulses. Numerous studies indicated beneficial effect of rTMS in several neurological diseases, including AD, however, exact mechanism are yet to be elucidated. We aimed to evaluate the effect of intermittent theta burst stimulation (iTBS), an rTMS paradigm, on behavioral, neurochemical and molecular level in trimethyltin (TMT)-induced Alzheimer’s-like disease model. TMT acts as a neurotoxic agent targeting hippocampus causing cognitive impairment and neuroinflammation, replicating behavioral and molecular aspects of AD. Male Wistar rats were divided into four experimental groups–controls, rats subjected to a single dose of TMT (8 mg/kg), TMT rats subjected to iTBS two times per day for 15 days and TMT sham group. After 3 weeks, we examined exploratory behavior and memory, histopathological and changes on molecular level. TMT-treated rats exhibited severe and cognitive deficit. iTBS-treated animals showed improved cognition. iTBS reduced TMT-induced inflammation and increased anti-inflammatory molecules. We examined PI3K/Akt/mTOR signaling pathway which is involved in regulation of apoptosis, cell growth and learning and memory. We found significant downregulation of phosphorylated forms of Akt and mTOR in TMT-intoxicated animals, which were reverted following iTBS stimulation. Application of iTBS produces beneficial effects on cognition in of rats with TMT-induced hippocampal neurodegeneration and that effect could be mediated via PI3K/Akt/mTOR signaling pathway, which could candidate this protocol as a potential therapeutic approach in neurodegenerative diseases such as AD.

show abstract

Section: Discussionmentioning

confidence: 94%

Intermittent Theta Burst Stimulation Ameliorates Cognitive Deficit and Attenuates Neuroinflammation via PI3K/Akt/mTOR Signaling Pathway in Alzheimer’s-Like Disease Model

Stekic

Zeljković

Kontic

et al. 2022

Front. Aging Neurosci.

View full text Add to dashboard Cite

show abstract

“…Six hours after modeling, the neural function of experimental rats was evaluated in the form of scoring, and Logna scoring method was adopted [ 25 ]. The rats were divided into five grades according to their behaviors: 0 point, no symptoms of nerve damage; 1 point, left front paw cannot be fully extended; 2 points, when walking, the rats turned to the left side (paralyzed side); 3 points, when walking, the rat body tipped to the left side (paralyzed side); 4 points, cannot walk spontaneously, conscious loss.…”

Section: Methodsmentioning

confidence: 99%

The Differences of Metabolites in Different Parts of the Brain Induced by Shuxuetong Injection against Cerebral Ischemia-Reperfusion and Its Corresponding Mechanism

Jiang

Jiao

Shang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Ischemic stroke is often associated with a large disease burden. The existence of ischemia-reperfusion injury brings great challenges to the treatment of ischemic stroke. The purpose of this study was to explore the differences of metabolites in different parts of the brain induced by Shuxuetong injection against cerebral ischemia-reperfusion and to extend the corresponding mechanism. The rats were modeled by transient middle cerebral artery occlusion (t-MCAO) operation, and the success of modeling was determined by neurological function score and TTC staining. UPLC-Q/TOF-MS metabolomics technique and multivariate statistical analysis were used to analyze the changes and differences of metabolites in the cortex and hippocampus of cerebral ischemia-reperfusion rats. Compared with the model group, the neurological function score and cerebral infarction volume of the Shuxuetong treatment group were significantly different. There were differences and changes in the metabolic distribution of the cortex and hippocampus in each group, the distribution within the group was relatively concentrated. The separation trend between the groups was obvious, and the distribution of the Shuxuetong treatment group was similar to that of the sham operation group. We identified 13 metabolites that were differentially expressed in the cortex, including glutamine, dihydroorotic acid, and glyceric acid. We also found five differentially expressed metabolites in the hippocampus, including glutamic acid and fumaric acid. The common metabolic pathways of Shuxuetong on the cortex and hippocampus were D-glutamine and D-glutamate metabolism and nitrogen metabolism, which showed inhibition of cortical glutamine and promotion of hippocampal glutamic acid. Specific pathways of Shuxuetong enriched in the cortex included glyoxylate and dicarboxylate metabolism and pyrimidine metabolism, which showed inhibition of glyceric acid and dihydroorotic acid. Specific pathways of Shuxuetong enriched in the hippocampus include arginine biosynthesis and citrate cycle (TCA cycle), which promotes fumaric acid. Shuxuetong injection can restore and adjust the metabolic disorder of the cortex and hippocampus in cerebral ischemia-reperfusion rats. The expression of Shuxuetong in different parts of the brain is different and correlated.

show abstract

“…TMS is a noninvasive form of neuromodulation that has been widely applied in TBI due to promising initial results in neuroprotection and recovery in preclinical models [60,61]. While the molecular mechanisms underlying the effects of TMS are not fully understood, in models of cerebral ischemia TMS has shown the ability to modulate neuroinflammation through inhibition of NF-kB and promotion of microglia M2 polarization [62], as well as antioxidant effects through upregulation of antioxidant enzyme transcription factors [63], making TMS theoretically a useful intervention early in the acute phase of TBI. TMS has been extensively applied as a monomodal therapy, but has also been used in two clinical trials as part of a combination.…”

Section: Multimodal Nonpharmacologic Interventionsmentioning

confidence: 99%

“…However, much like for pharmacologic interventions, the blind application of non-pharmacologic treatment techniques without a detailed understanding of the patient's physiologic state at the time of application as well as knowledge of the molecular targets of the intervention is likely to fail. As an example, TMS has been shown in ischemic brain tissue to work in part through induction of anti-oxidative enzymes [63] and inhibition of NF-kB [62], suggesting that TMS may be most effective if applied as part of a multimodal treatment regimen in the acute phase of TBI. Just as multimodal imaging and neuromonitoring have shown potential to guide pharmacologic therapies for TBI, they have also helped inform non-pharmacologic treatments.…”

Section: Future Directions In Multimodal Tbi Treatmentmentioning

confidence: 99%

Multi-mechanistic Approaches to the Treatment of Traumatic Brain Injury: A Review

Lynch¹,

Narayan²,

Li³

2023

Preprint

View full text Add to dashboard Cite

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Despite extensive research efforts, the majority of trialed monotherapies to date have failed to demonstrate significant benefit. It has been suggested that this is due to the complex pathophysiology of TBI, which may possibly be addressed by a combination of therapeutic interventions. In this article, we have reviewed combinations of different pharmacologic treatments, combinations of non-pharmacologic interventions, and combined pharmacologic and non-pharmacologic interventions for TBI. Both preclinical and clinical studies have been included. While promising results have been found in animal models, clinical trials of combination therapies have not yet shown clear benefit. This may possibly be due to their application without consideration of the evolving pathophysiology of TBI. Improvements of this paradigm may come from novel interventions guided by multimodal neuromonitoring and multimodal imaging techniques, as well as the application of multi-targeted non-pharmacologic and endogenous therapies. There also needs to be a greater representation of female subjects in preclinical and clinical studies.

show abstract

Repetitive Transcranial Magnetic Stimulation Improves Neuropathy and Oxidative Stress Levels in Rats with Experimental Cerebral Infarction through the Nrf2 Signaling Pathway

Cited by 14 publications

References 30 publications

Intermittent Theta Burst Stimulation Ameliorates Cognitive Deficit and Attenuates Neuroinflammation via PI3K/Akt/mTOR Signaling Pathway in Alzheimer’s-Like Disease Model

Intermittent Theta Burst Stimulation Ameliorates Cognitive Deficit and Attenuates Neuroinflammation via PI3K/Akt/mTOR Signaling Pathway in Alzheimer’s-Like Disease Model

The Differences of Metabolites in Different Parts of the Brain Induced by Shuxuetong Injection against Cerebral Ischemia-Reperfusion and Its Corresponding Mechanism

Multi-mechanistic Approaches to the Treatment of Traumatic Brain Injury: A Review

Contact Info

Product

Resources

About