isolation-flow-cytometric-assessment-neuroimmune-interactions-mini

Isolation and Flow Cytometric Assessment of Neuroimmune Interactions in a Mini-Stroke Murine Model

Stroke is a leading cause of death and long-term disability worldwide, with ischemic stroke representing the majority of cases. Following an ischemic ...

Capital Medical University

The current study aimed to investigate the prevalence and risk factors of restless legs syndrome (RLS) in patients undergoing hemodialysis, as well as the mortality and risks of cardiovascular and cerebrovascular events.

Prevalence and Risk Factors of Restless Legs Syndrome in Hemodialysis Patients.

Chronic cerebral hypoperfusion is associated with vascular cognitive impairment, and there are no specific therapeutic agents for use in clinical practice. Berberine has demonstrated good neuroprotective effects in models of acute cerebral ischemia; however, whether it can alleviate cognitive impairment caused by chronic cerebral hypoperfusion has rarely been investigated.

Berberine Ameliorates Cognitive Impairment by Regulating Microglial Polarization and Increasing Expression of Anti-inflammatory Factors following Permanent Bilateral Common Carotid Artery Occlusion in Rats.

Constipation is one of the common non-motor symptoms in Parkinson's disease that significantly impacts patient quality of life. Probiotics supplementation may improve constipation symptoms, but its effect on the gut microbiota population is unclear.

Probiotics for constipation and gut microbiota in Parkinson's disease.

Transcranial photobiomodulation refers to irradiation of the brain through the skull using low-intensity red or near-infrared light, which is the most commonly studied method of light energy biotherapy for central nervous system disorders. The absorption of photons by specific chromophores within the cell elevates ATP synthesis, reduces oxidative stress damage, alleviates inflammation or mediates the activation of transcription factors and signaling mediators through secondary mediators, which in turn trigger downstream signaling pathways to cause a series of photobiological effects including upregulation of neurotrophic factors. Multiple mechanisms are simultaneously involved in the pathological process of central nervous system disorders. The pleiotropic treatment of transcranial photobiomodulation towards multiple targets plays a beneficial role in improving hemodynamics, neural repair and improving behaviors in central nervous system disorders such as ischemic stroke, traumatic brain injury, neurodegenerative diseases, epilepsy and depression. This review mainly introduces the mechanism and recent preclinical and clinical advances of transcranial photobiomodulation for central nervous system disorders, which will provide a reference for clinicians to understand and engage in related studies, and calls for more and larger studies to validate and develop a wider application of transcranial photobiomodulation in central nervous system.

Recent advances in light energy biotherapeutic strategies with photobiomodulation on central nervous system disorders.

Hirschsprung's disease is a congenital malformation characterized by the absence of enteric ganglia in the distal intestine and gut obstruction. Our previous study indicates the brain pathology during the disease progression. A subpopulation of Hirschsprung's disease patients is also associated with anomalies of the central nervous system. In the investigation, we studied a rat model of Hirschsprung's disease, known as spotting lethal (/) ET rats, which carries a spontaneous deletion in endothelin receptor B (human gene name: ) and manifests a similar phenotype as humans with Hirschsprung's disease. Homozygous mutant / rats were successfully rescued from premature death by performing colostomy and dramatically survived to their juvenile age. By the body weight measured, their body growth was not revealed to be significantly different between ET and wildtype ET or heterozygous (+/) ET groups while all underwent the same colostomy. Cell loss was investigated in several brain regions by using terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay (TUNEL) in ET, ET, and ET rats. Number of TUNEL-positive cells in the cerebellum and the hippocampus of ET rats was significantly increased compared with that of the ET and ET rats. TUNEL-positive cells were observed in the molecular layer and granular cell layers of the cerebellum. In contrast, no significant difference in the density of TUNEL-positive cells was revealed in the cerebral cortex. These results suggest that either endothelin receptor B  mutation or colostomy has predominant lasting effects on the cell survival/loss in the cerebellum and hippocampus of adult ET rats. Our findings provide the information on cellular changes in the brains of patients with Hirschsprung's disease due to congenital  mutation as well as clinically relevant interventions.

Colostomy Delays Cell Loss in the Brain and Improves Juvenile Survival in a Neonatal Rat Model of Hirschsprung's Disease.

Emerging evidence suggests that dysbiosis of the gut microbiota is associated with the pathogenesis of Parkinson's disease (PD), a prevalent neurodegenerative disorder. The microbiota-gut-brain axis plays a crucial role in the development and progression of PD, and numerous studies have demonstrated the potential therapeutic benefits of modulations in the intestinal microbiota. This review provides insights into the characterization of the gut microbiota in patients with PD and highlights associations with clinical symptoms and underlying mechanisms. The discussion underscores the increased influence of the gut microbiota in the pathogenesis of PD. While the relationship is not fully elucidated, existing research demonstrates a strong correlation between changes in the composition of gut microbiota and disease development, and further investigation is warranted to explain the specific underlying mechanisms.

Gut microbiota and Parkinson's disease.

Stroke is a major global cause of death and disability, with ischemic stroke being the most common type. The disruption of the blood-brain barrier (BBB) is a key factor in the pathophysiology of ischemic stroke, allowing immune cells to infiltrate and worsening neuroinflammation. This study uses single-cell RNA sequencing (scRNA-seq) to examine the transcriptional changes in neutrophils, endothelial cells, and T cells during ischemic stroke. Our findings indicate a significant increase in neutrophil and lymphocyte infiltration, along with a notable decrease in endothelial cell populations, demonstrating severe BBB disruption. Differential gene expression analysis shows that endothelial cells lose important characteristics post-stroke, while lymphocytes activate cytotoxic pathways that may lead to neuronal damage. Additionally, we reveal the contrasting roles of CXCR2 and CXCR4 in neutrophil movement and identify neutrophil-derived damage-associated molecular patterns (DAMPs) and matrix metalloproteinases (MMPs) as key drivers of endothelial cell apoptosis. Notably, the S100A8/A9 inhibitor paquinimod significantly protects neurons and reduces lymphocyte infiltration, suggesting that targeting S100A8/A9 could be a promising therapeutic strategy for reducing neurological deficits after ischemic stroke. Overall, these results enhance our understanding of the complex interactions between immune cells and the BBB in ischemic stroke, paving the way for innovative therapeutic approaches aimed at maintaining brain integrity and improving patient outcomes.

Single-cell RNA sequencing reveals S100A8/A9 neutrophils-induced endothelial cell death and lymphocyte infiltration after ischemic stroke.

Previous research has commonly regarded overactive bladder syndrome (OAB) and restless legs syndrome (RLS) as distinct disorders in terms of their underlying causes, clinical diagnosis, and treatment approaches. However, there is evidence of an overlap in the occurrence of these two conditions following cerebral infarction(CI). Specifically, restless bladder syndrome (RBS), a subtype of RLS, exhibits symptoms similar to those of OAB. Consequently, further investigation is warranted to better understand the relationship between these two disorders.

Secondary overactive bladder syndrome with restless legs syndrome following cerebral infarction: report of 2 cases.

Stroke is a worldwide leading cause of death and long-term disability, with ischemic strokes making up approximately 85% of all cases. There is a significant need for an ideal animal model that accurately replicates the disease's pathology to study the molecular mechanisms of brain injury. Various experimental models have been created to induce middle cerebral artery occlusion (MCAO), including intraluminal MCAO, photothrombotic models, endothelin-1 injections, and electrocoagulation. However, these often result in large infarct or lesion volumes accompanied by considerable variability. In this study, we present a ministroke model that specifically targets the mouse barrel cortex, making it suitable for investigating the mechanisms of minor strokes and stroke recurrence. In our model, the distal branch of the right middle cerebral artery (MCA), which supplies the sensorimotor cortex, is permanently ligated using 10-0 sutures. This is followed by a 7-min occlusion of the bilateral common carotid arteries (CCAs) and subsequent reperfusion. This approach produces a mild stroke characterized by small and consistent lesion volumes and very low mortality rates. A well-trained experimenter can achieve nearly zero mortality with this technique. Furthermore, this model of localized ischemia induces lesions in the functionally defined barrel cortex, allowing the use of the vibrissae-evoked forelimb placing test to assess functional outcomes. Key features • Introduces a novel ministroke model targeting the mouse barrel cortex, specifically designed for studying minor strokes. • Achieves consistently small infarct sizes and low mortality rates, allowing for long-term assessments of functional outcomes. • Requires specialized surgical skills for the permanent ligation of the right middle cerebral artery and temporary occlusion of common carotid arteries. • The adhesive removal test and the vibrissae-evoked forelimb placing test exhibit remarkable sensitivity in this model.

Article	Year
Prevalence and Risk Factors of Restless Legs Syndrome in Hemodialysis Patients. Nature and science of sleep\| PubMed ID: 32021521	2020
Berberine Ameliorates Cognitive Impairment by Regulating Microglial Polarization and Increasing Expression of Anti-inflammatory Factors following Permanent Bilateral Common Carotid Artery Oc... CNS & neurological disorders drug targets\| PubMed ID: 35142272	2022
Probiotics for constipation and gut microbiota in Parkinson's disease. Parkinsonism & related disorders\| PubMed ID: 36087572	2022
Recent advances in light energy biotherapeutic strategies with photobiomodulation on central nervous system disorders. Brain research\| PubMed ID: 37783261	2024
Colostomy Delays Cell Loss in the Brain and Improves Juvenile Survival in a Neonatal Rat Model of Hirschsprung's Disease. Oxidative medicine and cellular longevity\| PubMed ID: 38094663	2022
Gut microbiota and Parkinson's disease. Chinese medical journal\| PubMed ID: 39501822	2025
Single-cell RNA sequencing reveals S100A8/A9 neutrophils-induced endothelial cell death and lymphocyte infiltration after ischemic stroke. Biochemical and biophysical research communications\| PubMed ID: 39579533	2024
Secondary overactive bladder syndrome with restless legs syndrome following cerebral infarction: report of 2 cases. BMC geriatrics\| PubMed ID: 40133822	2025
Developing a Ministroke Model in Mouse Barrel Cortex. Bio-protocol\| PubMed ID: 40395851	2025

Yitong Du

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