TREM2 mediates physical exercise-promoted neural functional recovery in rats with ischemic stroke via microglia-promoted white matter repair.

BACKGROUND: The repair of white matter injury is of significant importance for functional recovery after ischemic stroke, and the up-regulation of triggering receptors expressed on myeloid cells 2 (TREM2) after ischemic stroke is neuroprotective and implicated in remyelination. However, the lack of effective therapies calls for the need to investigate the regenerative process of remyelination and the role of rehabilitation therapy. This study sought to investigate whether and how moderate physical exercise (PE) promotes oligodendrogenesis and remyelination in rats with transient middle cerebral artery occlusion (tMCAO). METHODS: Male Sprague-Dawley rats (weighing 250-280 g) were subjected to tMCAO. AAV-shRNA was injected into the lateral ventricle to silence the Trem2 gene before the operation. The rats in the physical exercise group started electric running cage training at 48 h after the operation. The Morris water maze and novel object recognition test were used to evaluate cognitive function. Luxol fast blue staining, diffusion tensor imaging, and electron microscopy were used to observe myelin injury and repair. Immunofluorescence staining was applied to observe the proliferation and differentiation of oligodendrocyte precursor cells (OPCs). Expression of key molecules were detected using immunofluorescence staining, quantitative real-time polymerase chain reaction, Western blotting, and Enzyme-linked immunosorbent assay, respectively. RESULTS: PE exerted neuroprotective efects by modulating microglial state, promoting remyelination and recovery of neurological function of rats over 35 d after stroke, while silencing Trem2 expression in rats suppressed the aforementioned effects promoted by PE. In addition, by leveraging the activin-A neutralizing antibody, we found a direct beneficial effect of PE on microglia-derived activin-A and its subsequent role on oligodendrocyte differentiation and remyelination mediated by the activin-A/Acvr axis. CONCLUSIONS: The present study reveals a novel regenerative role of PE in white matter injury after stroke, which is mediated by upregulation of TREM2 and microglia-derived factor for oligodendrocytes regeneration. PE is an effective therapeutic approach for improving white matter integrity and alleviating neurological function deficits after ischemic stroke.

Chronic colitis exacerbates NLRP3-dependent neuroinflammation and cognitive impairment in middle-aged brain.

BACKGROUND: Neuroinflammation is a major driver of age-related brain degeneration and concomitant functional impairment. In patients with Alzheimer's disease, the most common form of age-related dementia, factors that enhance neuroinflammation may exacerbate disease progression, in part by impairing the glymphatic system responsible for clearance of pathogenic beta-amyloid. Inflammatory bowel diseases (IBDs) induce neuroinflammation and exacerbate cognitive impairment in the elderly. The NACHT-LRR and pyrin (PYD) domain-containing protein 3 (NLRP3) inflammasome has been implicated in neuroinflammation. Therefore, we examined if the NLRP3 inflammasome contributes to glymphatic dysfunction and cognitive impairment in an aging mouse model of IBD. METHODS: Sixteen-month-old C57BL/6J and NLRP3 knockout (KO) mice received 1% wt/vol dextran sodium sulfate (DSS) in drinking water to model IBD. Colitis induction was confirmed by histopathology. Exploratory behavior was examined in the open field, associative memory by the novel-object recognition and Morris water maze tests, glymphatic clearance by in vivo two-photon imaging, and neuroinflammation by immunofluorescence and western blotting detection of inflammatory markers. RESULTS: Administration of DSS induced colitis, impaired spatial and recognition memory, activated microglia, and increased A1-like astrocyte numbers. In addition, DSS treatment impaired glymphatic clearance, aggravated amyloid plaque accumulation, and induced neuronal loss in the cortex and hippocampus. These neurodegenerative responses were associated with increased NLRP3 inflammasome expression and accumulation of gut-derived T lymphocytes along meningeal lymphatic vessels. Conversely, NLRP3 depletion protected against cognitive dysfunction, neuroinflammation, and neurological damage induced by DSS. CONCLUSIONS: Colitis can exacerbate age-related neuropathology, while suppression of NLRP3 inflammasome activity may protect against these deleterious effects of colitis.

Bioinformatic Analysis of Exosomal MicroRNAs of Cerebrospinal Fluid in Ischemic Stroke Rats After Physical Exercise.

Physical exercise is beneficial to the structural and functional recovery of post-ischemic stroke, but its molecular mechanism remains obscure. Herein, we aimed to explore the underlying mechanism of exercise-induced neuroprotection from the perspective of microRNAs (miRNAs). Adult male Sprague-Dawley (SD) rats were randomly distributed into 4 groups, i.e., the physical exercise group with the transient middle cerebral artery occlusion (tMCAO) surgery (PE-IS, n = 28); the physical exercise group without tMCAO surgery (PE, n = 6); the sedentary group with tMCAO surgery (Sed-IS, n = 28); and the sedentary group without tMCAO surgery (Sed, n = 6). Notably, rats in the PE-IS and PE groups were subjected to a running exercise for 28 days while rats in the Sed-IS and Sed groups received no exercise training. After long-term exercise, exosomal miRNAs of cerebrospinal fluid (CSF) were analyzed using high-throughput sequencing. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were employed for the differentially expressed miRNAs. Physical exercise improved the neurological function and attenuated the lesion expansion after stroke. In total, 41 differentially expressed miRNAs were screened for the GO and KEGG analysis. GO enriched terms were associated with the central nervous system, including cellular response to retinoic acid, vagus nerve morphogenesis, cellular response to hypoxia, dendritic cell chemotaxis, cell differentiation, and regulation of neuron death. Besides, these differentially expressed miRNAs were linked to the pathophysiological process of stroke, including axon guidance, NF-kappa B signaling pathway, thiamine metabolism, and MAPK signaling pathway according to KEGG analysis. In summary, exercise training significantly alleviated the neurological damage at both functional and structural levels. Moreover, the differentially expressed miRNAs regulating multiple signal pathways were potentially involved in the neuroprotective effects of physical exercise. Therefore, these miRNAs altered by physical exercise might represent the therapeutic strategy for cerebral ischemia.

Effects of transcranial magnetic stimulation on the performance of the activities of daily living and attention function after stroke: a randomized controlled trial.

OBJECTIVE: We aimed to interrogate the effects of transcranial magnetic stimulation (TMS) on the performance in activities of daily living (ADL) and attention function after stroke. DESIGN: Randomized controlled trial. SETTING: Inpatient rehabilitation hospital. SUBJECTS: We randomized 62 stroke patients with attention dysfunction who were randomly assigned into two groups, and two dropped out from each group. The TMS group (n = 29) and a sham group (n = 29), whose mean (SD) was 58.12 (6.72) years. A total of 33 (56.9%) patients had right hemisphere lesion while the rest 25 (43.1%) patients had left hemisphere lesion. INTERVENTIONS: Patients in the TMS group received 10 Hz, 700 pulses of TMS, while those in the sham group received sham TMS for four weeks. All the participants underwent comprehensive cognitive training. MAIN MEASURES: At baseline, and end of the four-week treatment, the performance in the activities of daily living was assessed by Functional Independence Measure (FIM). On the other side, attention dysfunction was screened by Mini-Mental State Examination (MMSE), while the attention function was assessed by the Trail Making Test-A (TMT-A), Digit Symbol Test (DST) and Digital Span Test (DS). RESULTS: Our data showed a significant difference in the post-treatment gains in motor of Functional Independence Measure (13.00 SD 1.69 vs 4.21 SD 2.96), cognition of Functional Independence Measure (4.69 SD 1.56 vs 1.52 SD 1.02), total of Functional Independence Measure (17.69 SD 2.36 vs 5.72 SD 3.12), Mini-Mental State Examination (3.07 SD 1.36 vs 1.21 SD 0.62), time taken in Trail Making Test-A (96.67 SD 25.18 vs 44.28 SD 19.45), errors number in Trail Making Test-A (2.72 SD 1.03 vs 0.86 SD 1.03), Digit Symbol Test (3.76 SD 1.09 vs 0.76 SD 0.87) or Digital Span Test (1.69 SD 0.54 vs 0.90 SD 0.72) between the TMS group and the sham group (P < 0.05). CONCLUSIONS: Taken together, we demonstrate that TMS improves the performance in the activities of daily living and attention function in patients with stroke.

Juvenile treatment with a novel mGluR2 agonist/mGluR3 antagonist compound, LY395756, reverses learning deficits and cognitive flexibility impairments in adults in a neurodevelopmental model of schizophrenia.

Schizophrenia (SCZ) is a neurodevelopmental psychiatric disorder, in which cognitive function becomes disrupted at early stages of the disease. Although the mechanisms underlying cognitive impairments remain unclear, N-methyl-D-aspartate receptors (NMDAR) hypofunctioning in the prefrontal cortex (PFC) has been implicated. Moreover, cognitive symptoms in SCZ are usually unresponsive to treatment with current antipsychotics and by onset, disruption of the dopamine system, not NMDAR hypofunctioning, dominates the symptoms. Therefore, treating cognitive deficits at an early stage is a realistic approach. In this study, we tested whether an early treatment targeting mGluR2 would be effective in ameliorating cognitive impairments in the methylazoxymethanol acetate (MAM) model of SCZ. We investigated the effects of an mGluR2 agonist/mGluR3 antagonist, LY395756 (LY39), on the NMDAR expression and function in juveniles, as well as cognitive deficits in adult rats after juvenile treatment. We found that gestational MAM exposure induced a significant decrease in total protein levels of the NMDAR subunit, NR2B, and a significant increase of pNR2BTyr1472 in the juvenile rat PFC. Treatment with LY39 in juvenile MAM-exposed rats effectively recovered the disrupted NMDAR expression. Furthermore, a subchronic LY39 treatment in juvenile MAM-exposed rats also alleviated the learning deficits and cognitive flexibility impairments when tested with a cross-maze based set-shifting task in adults. Therefore, our study demonstrates that targeting dysfunctional NMDARs with an mGluR2 agonist during the early stage of SCZ could be an effective strategy in preventing the development and progression in addition to ameliorating cognitive impairments of SCZ.

High-Frequency Repetitive Transcranial Magnetic Stimulation (rTMS) Improves Functional Recovery by Enhancing Neurogenesis and Activating BDNF/TrkB Signaling in Ischemic Rats.

Repetitive transcranial magnetic stimulation (rTMS) has rapidly become an attractive therapeutic approach for stroke. However, the mechanisms underlying this remain elusive. This study aimed to investigate whether high-frequency rTMS improves functional recovery mediated by enhanced neurogenesis and activation of brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) pathway and to compare the effect of conventional 20 Hz rTMS and intermittent theta burst stimulation (iTBS) on ischemic rats. Rats after rTMS were sacrificed seven and 14 days after middle cerebral artery occlusion (MCAO), following evaluation of neurological function. Neurogenesis was measured using specific markers: Ki67, Nestin, doublecortin (DCX), NeuN and glial fibrillary acidic protein (GFAP), and the expression levels of BDNF were visualized by Western blotting and RT-PCR analysis. Both high-frequency rTMS methods significantly improved neurological function and reduced infarct volume. Moreover, 20 Hz rTMS and iTBS significantly promoted neurogenesis, shown by an increase of Ki67/DCX, Ki67/Nestin, and Ki67/NeuN-positive cells in the peri-infarct striatum. These beneficial effects were accompanied by elevated protein levels of BDNF and phosphorylated-TrkB. In conclusion, high-frequency rTMS improves functional recovery possibly by enhancing neurogenesis and activating BDNF/TrkB signaling pathway and conventional 20 Hz rTMS is better than iTBS at enhancing neurogenesis in ischemic rats.

Physical exercise promotes recovery of neurological function after ischemic stroke in rats.

Although physical exercise is an effective strategy for treatment of ischemic stroke, the underlying protective mechanisms are still not well understood. It has been recently demonstrated that neural progenitor cells play a vital role in the recovery of neurological function (NF) through differentiation into mature neurons. In the current study, we observed that physical exercise significantly reduced the infarct size and improved damaged neural functional recovery after an ischemic stroke. Furthermore, we found that the treatment not only exhibited a significant increase in the number of neural progenitor cells and neurons but also decreased the apoptotic cells in the peri-infarct region, compared to a control in the absence of exercise. Importantly, the insulin-like growth factor-1 (IGF-1)/Akt signaling pathway was dramatically activated in the peri-infarct region of rats after physical exercise training. Therefore, our findings suggest that physical exercise directly influences the NF recovery process by increasing neural progenitor cell count via activation of the IGF-1/Akt signaling pathway.

[Effects of physical training on pyramidal tract regeneration in hypertensive rats with focal cerebral infarction].

OBJECTIVE: To explore the effects of exercise training on motor functional recovery and pyramidal tract regeneration in hypertensive rats with focal cerebral infarction. METHODS: Middle cerebral artery occlusion (MCAO) model was generated by electric coagulation on stroke-prone renovascular hypertensive Sprague-Dawley rats. The rats were randomly allocated to three groups of sham (n = 15), exercise training (n = 10) and control (n = 12). The exercise training group had running wheel exercise. The neurological function was evaluated with the modified neurological severity scores (mNSS) and forelimb grip strength test at Days 3, 7, 14, 21, 28, 35 and 42 post-ischemia. The pathological changes of neurons around infarct cortex were measured by Nissl staining. At Day 42 post-ischemia, anterograde tract tracers of biotinylated dextran amine (BDA) and cascade blue-labeled dextran amine (CB) were injected into cortex. And axonal extension of ipsi- and contra-lesional pyramidal tract was observed at Day 14 post-injection. RESULTS: The mNSS score declined in the exercise training group (4.0 ± 1.1, 2.7 ± 0.7, 2.6 ± 0.5) versus those in the control group (6.0 ± 1.3, 5.6 ± 1.0, 5.6 ± 1.1) at Days 28, 21 and 35 post-ischemia (all P < 0.01). The grip strength of paralytic forelimb increased in the exercise training group ((379 ± 41, 344 ± 15, 430 ± 48, 471 ± 47, 454 ± 17)g) versus those in the control group ((276 ± 8, 170 ± 5, 236 ± 12, 283 ± 14, 317 ± 15)g) at Days 14, 21, 28, 35 and 42 post-infarction (all P < 0.05). Compared with the control group (0.571 ± 0.060) , exercise training (0.734 ± 0.035) reduced neuron loss (P < 0.05). Moreover, the percentage of the number of BDA-positive, midline-crossing fibers over the number of labeled fibers in cerebral peduncle ipsilateral to injection site increased in the exercise training group (0.096 8 ± 0.022 6) versus those in the control group (0.014 2 ± 0.003 9) at the level of cervical enlargement (P < 0.016 7). The percentage of CB immunofluorescence in striatum ipsilateral to lesion-sided motor cortex over those in ischemic cortex was lower in the control group (0.521 ± 0.020) and the exercise training group (0.499 ± 0.034) than that in the sham group (0.824 ± 0.017) (all P < 0.01). However, no significant difference existed between control and exercise training groups (P > 0.05). CONCLUSION: Exercise training promotes the recovery of motor function and contralesional pyramidal tract regeneration after cerebral infarction.

Transthoracic Ultrasound Improves Cardiac Function in Mice.

Cardiac dysfunction is a severe complication that is associated with an increased risk of mortality in multiple diseases. Cardioprotection solution that has been researched is the electrical stimulation of the vagus nerve to exert cardio protection. This method has been shown to reduce the systemic inflammatory response and maintain the immune homeostasis of the heart. However, the invasive procedure of electrode implantation poses a risk of nerve or fiber damage. Here, we propose transthoracic ultrasound stimulation (US) of the vagus nerve to alleviate cardiac dysfunction caused by lipopolysaccharide (LPS). We developed a noninvasive transthoracic US system and exposed anesthetized mice to ultrasound protocol or sham stimulation 24 h after LPS treatment. Results showed that daily heart targeting US for 4 days significantly increased left ventricular systolic function ( p = 0.01) and improved ejection fraction ( p = 0.03) and shortening fraction ( p = 0.04). Furthermore, US significantly reduced inflammation cytokines, including IL-6 ( p = 0.03) and IL- 1ß ( p = 0.04). In addition, cervical vagotomy abrogated the effect of US, suggesting the involvement of the vagus nerve's anti-inflammatory effect. Finally, the same ultrasound treatment but for a longer period (14 days) also significantly increased cardiac function in naturally aged mice. Collectively, these findings suggest the potential of transthoracic US as a possible novel noninvasive approach in the context of cardiac dysfunction with reduced systolic function and provide new targets for rehabilitation of peripheral organ function.

High-frequency repetitive transcranial magnetic stimulation promotes neural stem cell proliferation after ischemic stroke.

JOURNAL/nrgr/04.03/01300535-202408000-00031/figure1/v/2023-12-16T180322Z/r/image-tiff Proliferation of neural stem cells is crucial for promoting neuronal regeneration and repairing cerebral infarction damage. Transcranial magnetic stimulation (TMS) has recently emerged as a tool for inducing endogenous neural stem cell regeneration, but its underlying mechanisms remain unclear. In this study, we found that repetitive TMS effectively promotes the proliferation of oxygen-glucose deprived neural stem cells. Additionally, repetitive TMS reduced the volume of cerebral infarction in a rat model of ischemic stroke caused by middle cerebral artery occlusion, improved rat cognitive function, and promoted the proliferation of neural stem cells in the ischemic penumbra. RNA-sequencing found that repetitive TMS activated the Wnt signaling pathway in the ischemic penumbra of rats with cerebral ischemia. Furthermore, PCR analysis revealed that repetitive TMS promoted AKT phosphorylation, leading to an increase in mRNA levels of cell cycle-related proteins such as Cdk2 and Cdk4. This effect was also associated with activation of the glycogen synthase kinase 3ß/ß-catenin signaling pathway, which ultimately promotes the proliferation of neural stem cells. Subsequently, we validated the effect of repetitive TMS on AKT phosphorylation. We found that repetitive TMS promoted Ca2+ influx into neural stem cells by activating the P2 calcium channel/calmodulin pathway, thereby promoting AKT phosphorylation and activating the glycogen synthase kinase 3ß/ß-catenin pathway. These findings indicate that repetitive TMS can promote the proliferation of endogenous neural stem cells through a Ca2+ influx-dependent phosphorylated AKT/glycogen synthase kinase 3ß/ß-catenin signaling pathway. This study has produced pioneering results on the intrinsic mechanism of repetitive TMS to promote neural function recovery after ischemic stroke. These results provide a strong scientific foundation for the clinical application of repetitive TMS. Moreover, repetitive TMS treatment may not only be an efficient and potential approach to support neurogenesis for further therapeutic applications, but also provide an effective platform for the expansion of neural stem cells.

Voluntary wheel exercise improves glymphatic clearance and ameliorates colitis-associated cognitive impairment in aged mice by inhibiting TRPV4-induced astrocytic calcium activity.

BACKGROUND AND OBJECTIVES: Chronic colitis exacerbates neuroinflammation, contributing to cognitive impairment during aging, but the mechanism remains unclear. The polarity distribution of astrocytic aquaporin 4 (AQP4) is crucial for the glymphatic system, which is responsible for metabolite clearance in the brain. Physical exercise (PE) improves cognition in the aged. This study aims to investigate the protective mechanism of exercise in colitis-associated cognitive impairment. METHODS: To establish a chronic colitis model, 18-month-old C57BL/6 J female mice received periodic oral administration of 1% wt/vol dextran sodium sulfate (DSS) in drinking water. The mice in the exercise group received four weeks of voluntary wheel exercise. High-throughput sequencing was conducted to screen for differentially expressed genes. Two-photon imaging was performed to investigate the function of the astrocytic calcium activity and in vivo intervention with TRPV4 inhibitor HC-067047. Further, GSK1016790A (GSK1), a TRPV4 agonist, was daily intraperitoneally injected during the exercise period to study the involvement of TRPV4 in PE protection. Colitis pathology was confirmed by histopathology. The novel object recognition (NOR) test, Morris water maze test (MWM), and open field test were performed to measure colitis-induced cognition and anxiety-like behavior. In vivo two-photon imaging and ex vivo imaging of fluorescent CSF tracers to evaluate the function of the glymphatic system. Immunofluorescence staining was used to detect the Aß deposition, polarity distribution of astrocytic AQP4, and astrocytic phenotype. Serum and brain levels of the inflammatory cytokines were tested by Enzyme-linked immunosorbent assay (ELISA). The brain TUNEL assay was used to assess DNA damage. Expression of critical molecules was detected using Western blotting. RESULTS: Voluntary exercise alleviates cognitive impairment and anxiety-like behavior in aged mice with chronic colitis, providing neuroprotection against neuronal damage and apoptosis. Additionally, voluntary exercise promotes the brain clearance of Aß via increased glymphatic clearance. Mechanistically, exercise-induced beneficial effects may be attributed, in part, to the inhibition of TRPV4 expression and TRPV4-related calcium hyperactivity, subsequent promotion of AQP4 polarization, and modulation of astrocyte phenotype. CONCLUSION: The present study reveals a novel role of voluntary exercise in alleviating colitis-related cognitive impairment and anxiety disorder, which is mediated by the promotion of AQP4 polarization and glymphatic clearance of Aß via inhibition of TRPV4-induced astrocytic calcium hyperactivity.

Correct Information Unit Analysis in Different Discourse Tasks Among Persons With Anomic Aphasia Based on Mandarin AphasiaBank.

PURPOSE: This study aimed to explore how well persons with anomic aphasia communicate information during discourse regarding quantity, quality, and efficiency compared to neurotypical controls, to investigate the influence of discourse tasks on informativeness and efficiency and to examine impact factors like aphasia severity and cognitive ability. METHOD: Language samples of four discourse tasks from 31 persons with anomic aphasia and 31 neurotypical controls were collected from Mandarin AphasiaBank. Correct information unit (CIU) analysis measures including the total number of CIUs, percentage of CIUs, CIUs per minute, and words per minute were calculated. Group differences and the effects of discourse tasks on informativeness and efficiency were investigated. Correlations of CIU analysis measures with aphasia severity and cognitive ability were examined. RESULTS: Persons with anomic aphasia showed lower efficiency in conveying information than controls. They underperformed controls on all CIU analysis measures when executing story narrative tasks. Discourse tasks influenced the informativeness and efficiency of both groups. Neurotypical controls delivered the greatest quantity of information most efficiently when narrating stories. Persons with anomic aphasia exhibited reduced quantity of information during procedural discourse and displayed superior information quality in sequential-picture descriptions. Discourse information may be impacted by aphasia severity and cognitive ability, with varying effects depending on the task. CONCLUSIONS: Persons with anomic aphasia are inefficient in communicating discourse messages and perform poorly on all measures in story narratives. When measuring discourse information, the effects of discourse tasks and factors like aphasia severity and cognitive ability should be considered.

Discourse Task Type-Specific Linguistic Characteristics in Anomic Aphasia and Healthy Controls: Evidence From Mandarin-Chinese AphasiaBank.

PURPOSE: This study was designed to examine the hypothesis that discourse task types influence language performance in Mandarin Chinese-speaking people and to reveal the discourse task-specific linguistic properties of persons with anomic aphasia compared to neurotypical controls. METHOD: Language samples from persons with aphasia (n = 31) and age- and education-matched controls (n = 31) across four discourse tasks (sequential-picture description, single-picture description, story narrative, and procedural discourse) were collected from Mandarin AphasiaBank. Task-specific distributions of parts of speech were analyzed using mosaic plots. The main effects of tasks in each group and the between-group differences within each task for several typical linguistic variables were evaluated, including the mean length of utterance, tokens, moving-average type-token ratio, words per minute, propositional density, noun-verb ratio, noun percentage, and verb percentage. RESULTS: The results revealed an impact of discourse tasks on most language variables in both groups. In the healthy controls, story narratives yielded the highest total words and lowest verb percentage. In the aphasia group, procedural discourse elicited the fewest total words and densest expressions, whereas their single-picture descriptions had the highest noun-verb ratio. For all tasks, the aphasia group performed worse than the control group in the mean length of utterance, tokens, moving-average type-token ratio, and words per minute. For noun-verb ratio, noun percentage, and verb percentage, only one task (i.e., single-picture description) showed significant between-group differences. CONCLUSION: The selection of discourse tasks should be addressed in assessments and interventions for Mandarin Chinese-speaking individuals with aphasia to obtain more accurate and feasible outcomes.

Interactions between tDCS treatment and COMT Val158Met in poststroke cognitive impairment.

OBJECTIVE: This study aimed to explore the effect of catechol-O-methyltransferase (COMT) Val158Met and brain-derived neurotrophic factor (BDNF) Val66Met to post-stroke cognitive impairment (PSCI) and the interaction with transcranial direct current stimulation (tDCS). METHODS: Seventy-six patients with PSCI were randomly assigned to Group (1) (n = 38) to receive anodal tDCS of left dorsolateral prefrontal cortex or Group (2) (n = 38) to receive sham stimulation. The intensity of the tDCS was 2 mA, and the stimulations were applied over the left DLPFC for 10 sessions. The Montreal Cognitive Assessment (MoCA) and backward digit span test (BDST) were assessed before, immediately after, and one month after stimulation. RESULTS: After stimulation, patients in the tDCS group showed better improvement in both MoCA and BDST than those in the sham group. The results of GLMs also supported the main effects of tDCS on general cognitive function and working memory. Then we found that COMT genotype may have a main effect on the improvement of MoCA and BDST, and there may be an interaction between COMT genotype and tDCS in enhancing BDST. In contrast, BDNF genotype showed no significant main or interaction effects on any scales. CONCLUSIONS: These findings demonstrate that tDCS can improve cognition after stroke. Gene polymorphisms of COMT can affect the efficacy of tDCS on PSCI, but BDNF may not. SIGNIFICANCE: This study found that COMT Val158Met has an interaction on the efficacy of prefrontal tDCS in cognitive function, which provides reference for future tDCS research and clinical application.

Physical exercise improves functional recovery through mitigation of autophagy, attenuation of apoptosis and enhancement of neurogenesis after MCAO in rats.

BACKGROUND: Physical exercise improves functional recovery after stroke through a complex mechanism that is not fully understood. Transient focal cerebral ischemia induces autophagy, apoptosis and neurogenesis in the peri-infarct region. This study is aimed to examine the effects of physical exercise on autophagy, apoptosis and neurogenesis in the peri-infarct region in a rat model of transient middle cerebral artery occlusion (MCAO). RESULTS: We found that autophagosomes, as labeled by microtubule-associated protein 1A light chain 3-II (LC3-II), were evident in the peri-infarct region at 3 days after 90-minute MCAO. Moreover, 44.6% of LC3-positive cells were also stained with TUNEL. The number of LC3 positive cells was significantly lower in physical exercise group than in control group at 14 and 21 days after MCAO. Suppression of autophagosomes by physical exercise was positively associated with improvement of neurological function. In addition, physical exercise significantly decreased the number of TUNEL-positive cells and increased the numbers of Ki67-positive, a proliferative marker, and insulin-like growth factor-1 (IGF-1) positive cells at 7, 14, and 21 days after MCAO. CONCLUSIONS: The present results demonstrate that physical exercise enhances neurological function possibly by reduction of autophagosome accumulation, attenuation of apoptosis and enhancement of neurogenesis in the peri-infarct region after transient MCAO in rats.

Effect of pelvic floor muscle training on pelvic floor muscle function and lower urinary tract symptoms in stroke patients: a systematic review.

BACKGROUND: Pelvic floor muscle (PFM) dysfunction and lower urinary tract symptoms (LUTS) are common in stroke patients. Although pelvic floor muscle training (PFMT) is a promising intervention, its effects on stroke patients have not been fully studied. OBJECTIVE: The goal of this study was to conduct a systematic review of the effect of PFMT on PFM and urinary function of stroke patients. METHODS: The databases AMED, MEDLINE, CINAHL, Cochrane Library, and PEDro were searched for title/abstract on PFMT and stroke. RCTs and quasi-experimental trials that compared the effects of PFMT to a control intervention in stroke patients were included. The RoB 2.0 and ROBINS-I were used to assess the methodological quality of the included studies. The Standardized mean difference (SMD) and its 95% confidence interval (CI) were calculated. RESULTS: The current review included three RCTs and one quasi-experimental study, all of which were moderate to high quality. The analysis revealed that PFMT significantly improved PFM contraction (SMD: 0.92; 95% CI, 0.47 to 1.38; p < .0001), dynamic endurance (SMD: 0.61; 95% CI, 0.06 to 1.16; p = .030), daytime frequency (SMD: -0.81; 95% CI, -1.37 to -0.25; p = .004), ICIQ-SF (SMD: -1.64; 95% CI, -2.39 to -0.89; p < .0001), and LUTS (SMD: -1.82; 95% CI, -2.67 to -0.96; p < .0001). Differences in PFM strength, static endurance, nocturia, UI frequency, and 24-hour pad weight were insignificant or non-existent between the two groups. CONCLUSION: This review demonstrates that PFMT improves PFM contraction, PFM dynamic endurance, daytime frequency, and overall LUTS in stroke patients. To validate these findings, well-designed RCTs with large sample sizes and reliable outcome measures should be conducted.

Effect of different mixing modes on the abundance of Microcystis in Lake Taihu under green light.

Light and hydrodynamic force are important physical factors affecting growth of Microcystis. The most recent study found that green light has good effect in inhibiting growth of Microcystis. To understand the effect of mixing modes on Microcystis under the green light, we investigated the effects of continuous mixing and intermittent mixing on the abundance of Microcystis in Taihu Lake under field conditions. The study results found that abundance of Microcystis in control, intermittent mixing group, and continuous mixing group decreased 76.62%, 40.36%, and 95.18% on day 7 compared with that on day 1 in this experiment. At the end of the experiment, abundance percentages of diatoms and green algae to total phytoplankton abundance were 1.57% and 0.48% in control, 2.32% and 0.67% in intermittent mixing group, and 22.47% and 20.27% in continuous mixing group. The results indicated that continuous mixing favored the removal of Microcystis under green light conditions and was helpful for the growth of green algae and diatoms. The results provide a new approach for the control of Microcystis blooms.

Exercise pretreatment alleviates neuroinflammation and oxidative stress by TFEB-mediated autophagic flux in mice with ischemic stroke.

BACKGROUND: Neuroinflammation and oxidative stress are important pathological mechanisms underlying cerebral ischemic stroke. Increasing evidence suggests that regulation autophagy in ischemic stroke may improve neurological functions. In this study, we aimed to explore whether exercise pretreatment attenuates neuroinflammation and oxidative stress in ischemic stroke by improving autophagic flux. METHODS: 2,3,5-Triphenyltetrazolium chloride staining was used to determine the infarction volume, and modified Neurological Severity Scores and rotarod test were used to evaluate neurological functions after ischemic stroke. The levels of oxidative stress, neuroinflammation, neuronal apoptosis and degradation, autophagic flux, and signaling pathway proteins were determined using immunofluorescence, dihydroethidium, TUNEL, and Fluoro-Jade B staining, western blotting, and co-immunoprecipitation. RESULTS: Our results showed that, in middle cerebral artery occlusion (MCAO) mice, exercise pretreatment improved neurological functions and defective autophagy, and reduced neuroinflammation and oxidative stress. Mechanistically, after using chloroquine, impaired autophagy abolished the neuroprotection of exercise pretreatment. And transcription factor EB (TFEB) activation mediated by exercise pretreatment contributes to improving autophagic flux after MCAO. Furthermore, we showed that TFEB activation mediated by exercise pretreatment in MCAO was regulated by the AMPK-mTOR and AMPK-FOXO3a-SKP2-CARM1 signaling pathways. CONCLUSIONS: Exercise pretreatment has the potential to improve the prognosis of ischemic stroke patients, and it can exert neuroprotective effects in ischemic stroke by inhibiting neuroinflammation and oxidative stress, which might be due to the TFEB-mediated autophagic flux. And targeting autophagic flux may be promising strategies for the treatment of ischemic stroke.

Screening diagnosis of executive dysfunction after ischemic stroke and the effects of transcranial magnetic stimulation: A prospective functional near-infrared spectroscopy study.

BACKGROUND: Post-ischemic stroke executive impairment (PISEI) is a serious obstacle for patients to returning to their society and is currently difficult to screen early and clinically ineffective. AIM: The aim of the study was to clarify whether functional near-infrared spectroscopy (fNIRS) can be used as a rapid screening tool for PISEI and to explore the efficacy of transcranial magnetic stimulation (TMS) in PISEI patients and the changes in brain function. METHODS: A single-blind, randomized controlled study design was used to detect hemodynamic differences by fNIIRS in 16 PISEI patients and 16 healthy subjects during the resting state and Stroop task, respectively. After 3 days, all subjects received a single TMS intervention and underwent simultaneous fNIRS testing for the Stroop task before and 3 days after the TMS intervention. RESULTS: PISEI patients had significantly higher HbO2 content in the left dorsolateral prefrontal cortex (DLPFC), the right pre-motor cortex (PMC) and the right primary sensorimotor cortex (SM1) during the Stroop task compared to the resting state (F = 141.966, p < 0.001), but significantly lower than healthy subjects (T = -3.413, p = 0.002). After TMS intervention, PISEI patients' time and error number scores on the Stroop test were significantly enhanced, and the functional activity of the above-mentioned brain regions was significantly more active than at baseline, while the strength of their functional connections with each other was markedly increased. CONCLUSIONS: fNIRS helped screen and diagnose PISEI. A single TMS session benefited PISEI patients with effects lasting 3 days, which may be attributed to activation of the left DLPFC, right PMC and right SM1 brain regions.