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.

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.

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.

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.

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.

Functional Alterations of the Basal Ganglia Are Associated with Voluntary Activation of the Core Stabilizing Muscles in Patients with Chronic Low Back Pain: A Cross-Sectional Study.

Purpose: Deficits in voluntary activation of the core stabilizing muscles are consistently observed in patients with chronic low back pain (CLBP); however, the underlying neural mechanism remains unclear. This cross-sectional study aimed at testing the hypothesis that the impaired voluntary activation of core stabilizing muscles is associated with structural and functional alterations in the basal ganglia, thalamus, and cortex in patients with CLBP. Methods: We obtained structural and resting-state functional magnetic resonance imaging (rs-fMRI) data from 53 patients with CLBP and 67 healthy controls and estimated the alterations in grey matter volume (GMV) and functional and effective connectivity (EC) of regions with altered GMV via whole brain analysis. The voluntary activation of the multifidus (MF) and transversus abdominis (TrA) was evaluated by ultrasound imaging in these patients. Results: Compared with the HCs, they displayed a significant decrease in GMV in the bilateral thalamus and caudate nucleus, a significant increase in GMV in the left middle frontal gyrus, and increased resting-state functional connectivity between the right caudate nucleus and the bilateral precuneus (voxel-level p < 0.005, Gaussian random field-corrected p < 0.05). The patients also showed increased EC from the right caudate nucleus to the bilateral precuneus, which was significantly correlated with voluntary activation of the bilateral MF and TrA (all p < 0.050). Conclusions: Grey matter alterations may be confined to regions responsible for perception, motor control, and emotion regulation in patients with CLBP. The interrupted EC from the basal ganglia to the default mode network might be involved in the impairment of voluntary activation of the core stabilizing muscles.

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.

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.

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.

Repetitive Transcranial Magnetic Stimulation Improves Neurological Function and Promotes the Anti-inflammatory Polarization of Microglia in Ischemic Rats.

Ischemic stroke (IS) is a severe neurological disease that is difficult to recovery. Previous studies have shown that repetitive transcranial magnetic stimulation (rTMS) is a promising therapeutic approach, while the exact therapy mechanisms of rTMS in improving neural functional recovery remain unclear. Furthermore, the inflammatory environment may influence the rehabilitation efficacy. Our study shows that long-term rTMS stimulation will significantly promote neurogenesis, inhibit apoptosis, and control inflammation. rTMS inhibits the activation of transcription factors nuclear factor kappa b (NF-κB) and signal transducer and activator of transcription 6 (STAT6) and promotes the anti-inflammatory polarization of microglia. Obvious promotion of anti-inflammatory cytokines production is observed both in vitro and in vivo through rTMS stimulation on microglia. In addition, neural stem cells (NSCs) cultured in conditioned medium (CM) from microglia treated with rTMS showed downregulation of apoptosis and upregulation of neuronal differentiation. Overall, our results illustrate that rTMS can modulate microglia with anti-inflammatory polarization variation, promote neurogenesis, and improve neural function recovery.

Ultrasound Stimulation of Prefrontal Cortex Improves Lipopolysaccharide-Induced Depressive-Like Behaviors in Mice.

Increasing evidence indicates that inflammatory responses may influence brain neurochemical pathways, inducing depressive-like behaviors. Ultrasound stimulation (US) is a promising non-invasive treatment for neuropsychiatric diseases. We investigated whether US can suppress inflammation and improve depressive-like behaviors. Mice were intraperitoneally injected with lipopolysaccharide to induce depressive-like behaviors. Ultrasound wave was delivered into the prefrontal cortex (PFC) for 30 min. Depressive- and anxiety-like behaviors were evaluated through the forced swimming test (FST), tail suspension test (TST), and elevated plus maze (EPM). Biochemical analyses were performed to assess the expression of inflammatory cytokines in the PFC and serum. The results indicated that US of the PFC significantly improved depressive-like behaviors in the TST (p < 0.05) and FST (p < 0.05). Anxiety-like behaviors also improved in the EPM (p < 0.05). Furthermore, the lipopolysaccharide-mediated upregulation of IL-6, IL-1ß, and TNF-α in the PFC was significantly reduced (p < 0.05) by US. In addition, no tissue damage was observed. Overall, US of PFC can effectively improve lipopolysaccharide-induced depressive-like behaviors, possibly through the downregulation of inflammatory cytokines in the PFC. US may be a safe and promising tool for improvement of depression.

Physical exercise promotes integration of grafted cells and functional recovery in an acute stroke rat model.

Human neural progenitor cell (hNPC) transplantation holds great potential to treat neurological diseases. However, hNPC grafts take a long time to differentiate into mature neurons due to their intrinsically prolonged developmental timetable. Here, we report that postoperative physical exercise (PE), a prevailing rehabilitation intervention, promotes the neuronal commitment, maturation, and integration of engrafted hNPCs, evidenced by forming more synapses, receiving more synaptic input from host neurons, and showing higher neuronal activity levels. More important, NPC transplantation, combined with PE, shows significant improvement in both structural and behavioral outcomes in stroke-damaged rats. PE enhances ingrowth of blood vessels around the infarction region and neural tract reorganization along the ischemic boundary. The combination of NPC transplantation and postoperative PE creates both a neurotrophic/growth factor-enriched proneuronal microenvironment and an ideal condition for activity-dependent plasticity to give full play to its effects. Our study provides a potential approach to treating patients with stroke injury.

Characteristics of systemic inflammation and brain iron deposition in Parkinson's disease patients.

OBJECTIVE: This study aimed at determining the characteristics of systemic inflammation and brain iron deposition in Parkinson's disease (PD) patients. METHODS: Thirty two PD patients and 30 gender- as well as age-matched controls were enrolled. Serum interleukin (IL)-1ß, IL-33, tumor necrosis factor (TNF)-α, IL-6, IL-10, ferritin, iron, and total iron binding capacity (TIBC) levels were assayed. Quantitative susceptibility mapping (QSM) was used to quantitatively analyze brain iron accumulation in the regions of interest (ROIs). Correlations between concentrations of inflammatory cytokines and biomarkers for peripheral iron metabolism, brain iron deposition were evaluated in the PD group. RESULTS: Serum concentrations of IL-1ß and IL-33 were found to be significantly elevated in the PD group compared to the control group, and in early-stage PD group compared to advanced-stage PD group. Total QSM value for bilateral ROIs was significantly elevated in the PD group compared to the control group, and in advanced-stage PD group compared to early-stage PD group. There was a significant inverse correlation between serum IL-1ß concentration and total QSM value for bilateral ROIs, between serum ferritin, iron, TIBC concentrations, and total QSM value for bilateral ROIs in PD patients. However, there was no significant correlation between serum IL-1ß concentrations and serum ferritin, iron, TIBC concentrations in PD patients. INTERPRETATION: The inflammatory state and chronic brain iron deposition progression in PD patients might be asynchronous. Alterations in systemic inflammation were not correlated with peripheral iron metabolism and might not contribute to the aggravation of brain iron deposition in PD patients.

Correlation of N30 somatosensory evoked potentials with spasticity and neurological function after stroke: A cross-sectional study.

OBJECTIVE: To test whether the presence of N30 somatosensory evoked potentials, generated from the supplementary motor area and premotor cortex, correlate with post-stroke spasticity, motor deficits, or motor recovery stage. DESIGN: A cross-sectional study. PATIENTS: A total of 43 patients with stroke hospitalized at Maoming People's Hospital, Maoming, China. METHODS: Forty-three stroke patients underwent neurofunctional tests, including Modified Ashworth Scale (MAS), Brunnstrom stage, manual muscle test and neurophysiological tests, including N30 somatosensory evoked potentials, N20 somatosensory evoked potentials, motor evoked potentials, H-reflex. The results were compared between groups. Correlation and regression analyses were performed as well. RESULTS: Patients with absence of N30 somatosensory evoked potential exhibited stronger flexor carpi radialis muscle spasticity (r = -0.50, p < 0.05) and worse motor function (r = 0.57, p < 0.05) than patients with presence of N30 somatosensory evoked potential. The generalized linear model (GLM) including both N30 somatosensory evoked potentials and motor evoked potentials (Akaike Information Criterion (AIC) = 121.99) better reflected the recovery stage of the affected proximal upper limb than the models including N30 somatosensory evoked potentials (AIC = 125.06) or motor evoked potentials alone (AIC = 127.45). CONCLUSION: N30 somatosensory evoked potential status correlates with the degrees of spasticity and motor function of stroke patients. The results showed that N30 somatosensory evoked potentials hold promise as a biomarker for the development of spasticity and the recovery of proximal limbs.

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.