Clinical application of repetitive transcranial magnetic stimulation in improving functional impairments post-stroke: review of the current evidence and potential challenges.

In recent years, the stroke incidence has been increasing year by year, and the related sequelae after stroke, such as cognitive impairment, motor dysfunction, and post-stroke depression, seriously affect the patient's rehabilitation and daily activities. Repetitive transcranial magnetic stimulation (rTMS), as a safe, non-invasive, and effective new rehabilitation method, has been widely recognized in clinical practice. This article reviews the application and research progress of rTMS in treating different functional impairments (cognitive impairment, motor dysfunction, unilateral spatial neglect, depression) after stroke in recent years, and preliminary summarized the possible mechanisms. It has been found that the key parameters that determine the effectiveness of rTMS in improving post-stroke functional impairments include pulse number, stimulated brain areas, stimulation intensity and frequency, as well as duration. Generally, high-frequency stimulation is used to excite the ipsilateral cerebral cortex, while low-frequency stimulation is used to inhibit the contralateral cerebral cortex, thus achieving a balance of excitability between the two hemispheres. However, the specific mechanisms and the optimal stimulation mode for different functional impairments have not yet reached a consistent conclusion, and more research is needed to explore and clarify the best way to use rTMS. Furthermore, we will identify the issues and challenges in the current research, explore possible mechanisms to deepen understanding of rTMS, propose future research directions, and offer insightful insights for better clinical applications.

Effects of dual-task training on gait and motor ability in patients with Parkinson's disease: A systematic review and meta-analysis.

OBJECTIVE: Parkinson's disease is one of the most common neurodegenerative diseases in the world, which seriously damages motor and balance ability. Dual-task training is discussed as an appropriate intervention. The aim of this review was to synthesize the existing research findings on the efficacy of dual-task training for people with Parkinson's disease. DATA RESOURCES: A systematic search on PubMed, CENTRAL, Embase, Web of Science, and PEDro, randomized-controlled trials (RCTs) of dual-task training for individuals with Parkinson's disease. METHODS: Articles published until 1 November 2022 were included. Our search identified 7 RCTs with a total of 406 subjects. Review Manager 5.4 software was used for bias evaluation and to process the results of the outcome measures collected from the investigations. RESULTS: Dual-task training was associated with significant improvement in most motor and balance outcomes including gait velocity (standard mean difference (SMD) = 0.62; 95% CI, 0.37-0.87; I2 = 31%; P = 0.21), cadence (SMD = 0.29; 95% CI, 0.05-0.53; I2 = 0%; P = 0.71), timed-up-and-go test (mean difference (MD) = -2.38; 95% CI, -3.93 to -0.84; I2 = 32%; P = 0.22) and mini-balance evaluation systems test (MD = 2.04; 95% CI, 1.05-3.03; I2 = 0%; P = 0.92). CONCLUSION: Evidence from meta-analyses suggests that dual-task training may improve motor and balance abilities in Parkinson's disease patients. Future research should focus on finding the most appropriate dual-task treatment model for patients with different degrees, in order to further improve the rehabilitation treatment of Parkinson's disease.

[Research advances on high-intensity interval training and cognitive function].

High-intensity interval training (HIIT) has proven to be a time-saving and efficient exercise strategy. Compared with traditional aerobic exercise, it can provide similar or even better health benefits. In recent years, a number of studies have suggested that HIIT could be used as a potential exercise rehabilitation therapy to improve cognitive impairment caused by obesity, diabetes, stroke, dementia and other diseases. HIIT may be superior to regular aerobic exercise. This article reviews the recent research progress on HIIT with a focus on its beneficial effect on brain cognitive function and the underlying mechanisms. HIIT may become an effective exercise for the prevention and/or improvement of brain cognitive disorder.

[Aerobic exercise reduces the expression of pyroptosis-related proteins and inflammatory factors in hippocampus of mice with insulin resistance].

The aim of the present study was to observe the expression of pyroptosis- and inflammation-related proteins in the hippocampus of mice with insulin resistance (IR) after aerobic exercise, and to explore the possible mechanism of exercise to improve IR. C57BL/6J male mice of 6 weeks old were randomly fed with normal diet (n = 12) and high-fat diet (HFD) (n = 26) for 12 weeks respectively. Glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed to determine whether IR occurred in HFD mice. Then the mice were randomly divided into control group (n = 12), IR group (n = 10) and IR + aerobic exercise group (AE, n = 10). Mice in AE group performed a 12-week progressive speed treadmill training after being adapted to the treadmill for one week. After the intervention, the expression of pyroptosis- and inflammation-related proteins in hippocampus was detected by Western blot. The results showed that compared with control group, NFκB, Nod-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing CARD (ASC), pyroptosis-related proteins like pro-Caspase-1, gasdermin D (GSDMD), GSDMD-N, and inflammatory factors IL-1ß, IL-18 were significantly increased. The inflammasome-related protein NIMA-related kinase 7 (NEK7) and pyroptosis-related protein Caspase-1 showed an increasing trend, but there was no significant difference. Compared with the IR group, progressive speed treadmill training significantly reduced the expression of NFκB, NLRP3, NEK7, ASC, pro-Caspase-1, GSDMD, GSDMD-N, IL-1ß, and IL-18 in the hippocampus of mice with IR. These results suggested 12-week progressive speed treadmill training can significantly reduce the expression of pyroptosis-related proteins and inflammatory factors in the hippocampus of mice with IR, and inhibit pyroptosis.

The Molecular Mechanisms of Excessive Hippocampal Endoplasmic Reticulum Stress Depressing Cognition-related Proteins Expression and the Regulatory Effects of Nrf2.

Studies have shown that obesity-induced hyperglycemia and hyperlipidemia could cause increased hippocampal endoplasmic reticulum (ER) stress and impaired cognition-related proteins expression, resulting in learning and memory impairment. Meanwhile, aerobic exercise could activate hippocampal nuclear factor erythroid 2-related factor 2 (Nrf2) reducing ER stress. This study investigated the underlying molecular mechanisms of this effect. In order to clarify the relationship among ER stress, Nrf2 signaling and cognition-related proteins expression in vitro, we respectively treated hippocampal cells with high glucose and palmitic acid (PA), ER stress inhibitor 4-phenylbutyrate (4-PBA), and Nrf2 activator Tert-Butylhydroquinone (TBHQ). Results showed that the expression levels of glucose transporter 3 (GLUT3), fatty acid transport protein 1 (FATP1), ER stress biomarkers (GRP78, p-PERK, p-IRE1α and p-eIF2α), ER stress-mediated apoptosis biomarkers (caspase-12, CHOP and Bax/Bcl-2), and the activity of NLRP3-IL-1ß inflammatory pathway were significantly increased under high glucose and PA conditions, accompanied with depressed p38/ERK-CREB pathway and decreased levels of brain derived neurotrophic factor (BDNF) and synaptophysin (SYN). On the other hand, both 4-PBA and TBHQ reduced ER stress and reversed the expression of the above-mentioned proteins. Our findings suggest that high glucose and PA could induce excessive ER stress and apoptosis via promoting the overexpression of GLUT3 and FATP1, and ER stress could suppress BDNF and SYN expression through negatively regulating p38/ERK-CREB pathway and positively regulating NLRP3-IL-1ß pathway, which could be reversed by activated Nrf2-HO-1 pathway.

[Effects of resistance exercise on pyroptosis-related proteins in hippocampus of insulin resistant mice].

Objective: To investigate the changes of pyroptosis-related proteins in the hippocampus of insulin-resistant mice and the regulation of resistance training on pyroptosis-related proteins. Methods: Six-week-old male C57BL/6J mice were randomly divided into control group (C, n=12) and high-fat diet group (HFD, n=26) for normal or high-fat diet for 12 weeks. Subsequently, according to the results of glucose tolerance test (GTT) and insulin tolerance test (ITT), the rats fed with high-fat diet were divided into insulin resistance group (IR, n=10) and resistance exercise group (RT, n=10) as well as to maintain high-fat diet. At the same time, mice in the RT group were subjected to resistance training. After 12 weeks, all mice were sacrificed after anesthesia, brain was removed and hippocampus was exfoliated, and the expressions of pyroptosis-related proteins were detected by Western blot. Results: Compared with the C group, NF-κB, the NLRP3 inflammasome proteins, their downstream pyroptosis-related proteins GSDMD-N and GSDMD as well as inflammation factors IL-1ß and IL-18 in hippocampus of IR group were significantly increased (P＜0.05), and the expression levels of SIRT1 and p-AMPK protein were significantly decreased (P＜0.05). Compared with the IR group, NF-κB, the NLRP3 inflammasome proteins, their downstream pyroptosis-related proteins GSDMD-N and GSDMD as well as inflammation factors IL-1ß and IL-18 in hippocampus of RT group were significantly decreased (P＜0.05), and the expression levels of SIRT1 and p-AMPK protein were significantly increased (P＜0.01). Conclusion: NLRP3 inflammasome in the hippocampus of insulin-resistant mice is activated, which mediates pyroptosis in the hippocampus. Twelve weeks of resistance training can effectively inhibit the activation of NLRP3 inflammasome and decrease pyroptosis and improve inflammation in the hippocampus.

[Research advances on anti-inflammatory, antioxidant and anti-apoptotic biological effects of methane].

Methane (CH4) is the simplest hydrocarbons and endogenous CH4 has been thought only to be generated by methanogens in the oral cavity and gastrointestinal tract of the mammals. However, recent animal studies have shown that endogenous CH4 can also be generated from choline and its metabolites in the mammals to protect the plasma membrane from reactive oxygen species attack and repair the membrane. In addition, exogenous CH4 can ameliorate the oxidative stress injury of multiple tissues and organs through its anti-inflammatory, antioxidant and anti-apoptosis effects. This paper reviews the recent researches about CH4 synthetic metabolism and biological functions, and highlights its potential of wide application in the prevention and treatment of oxidative stress related diseases and the significance for the development of gas medicine.