Zheng, Ruoyi

Multiple sclerosis (MS) is an immune-mediated chronic inflammatory and degenerative disease of the central nervous system (CNS). Typically occurring in young and middle-aged individuals, untreated MS can have high rates of disability and recurrence, thereby imposing a significant burden on the patient, their family, and society. Many factors are implicated in the etiology of MS, with the relationship between Epstein-Barr Virus (EBV) infection and the development of MS being the subject of extensive research recently. When the human body experiences a decline in immune function, it may trigger reactivation of EBV, and this reactivation is also believed to increase the risk of onset or relapse of MS. Currently, the phenomenon of cross-reactivity resulting from molecular mimicry following EBV infection (including reactivation status) is theorized as a contributing etiology. EBV-mediated abnormalities in T cells and B cells also play a key role in the development of MS. However, the underlying mechanisms have not been thoroughly understood. Meanwhile, the limited availability of effective treatment options for MS, in particular MS progression, underscores the urgent need for novel therapeutic strategies. Here, we discuss the pathophysiological mechanisms underlying MS, specifically emphasizing the relationship between EBV infection and the disease pathology. Furthermore, we introduced relevant pharmacological targets in order to propose a broader range of therapeutic alternatives for individuals diagnosed with MS.

Spinal cord stimulation (SCS), first used for pain relief in 1967, serves as an invasive neuromodulation with the targeted delivery of stimulations and the alertness of neural activities. Based on the gate-controlled theory of pain and multiple research studies, the application of SCS to motor recovery, pain relief, and sensory and cognitive restoration has been shown to be significant. Considering that movement disorders and pain are complications of various diseases, the categories, applications, and technical operation of SCS are coming of age. In terms of its impact on the immune system, SCS alters the trajectory of neurological diseases by modulating local immune responses through immunomodulatory mechanisms that vary depending on the different patterns of SCS. In addition to existing targets, the combinations of SCS and emerging techniques deepen the research at the molecular level, contributing to the exploration of potential targets and novel treatments. However, to secure a place in the future trend of non-invasive and precise treatment, it is necessary to improve SCS in terms of mechanism research, cost reduction, and application to more diseases.

IntroductionAlzheimer's disease (AD) is a neurodegenerative disease with neurogenic fiber tangles caused by amyloid-β protein plaques and tau protein hyperphosphorylation as the pathological manifestations. This study was based on multi-omics to investigate the mechanisms and immune characterization of AD.Material and methodsBased on bulk RNA-seq (GSE122063 and GSE97760), we screened potential biomarkers for AD by differential expression analysis and machine learning algorithms. Then, we elaborated the expression characteristics and immune functions of the above biomarkers by scRNA-seq (single-cell RNA sequencing) data analysis (GSM4996463 and GSM4996462) and immune infiltration analysis.ResultsFive biomarkers (RBM3, GOLGA8A, ALS2, FSD2, and LOC100287628) were identified using machine learning algorithms. Single-cell analysis revealed distinct expression patterns of these biomarkers in astrocytes from AD samples compared to normal samples. Additionally, three key biomarkers were selected based on interaction networks, and the diagnostic models indicated high diagnostic efficacy for these biomarkers. Based on immune infiltration and correlation analyses, RBM3, GOLGA8A, and ALS2 were all highly correlated with CD8 T cell content in the immune microenvironment of AD.ConclusionsThe biomarkers identified in this study demonstrate significant diagnostic potential for AD. Notably, the downregulation of RBM3 in astrocytes and the decreased presence of CD8 T cells infiltrating brain tissue are potential risk factors for AD.

: Cerebral Edema (CE) is the final common pathway of brain death. In severe neurological disease, neuronal cell damage first contributes to tissue edema, and then Increased Intracranial Pressure (ICP) occurs, which results in diminishing cerebral perfusion pressure. In turn, anoxic brain injury brought on by decreased cerebral perfusion pressure eventually results in neuronal cell impairment, creating a vicious cycle. Traditionally, CE is understood to be tightly linked to elevated ICP, which ultimately generates cerebral hernia and is therefore regarded as a risk factor for mortality. Intracranial hypertension and brain edema are two serious neurological disorders that are commonly treated with mannitol. However, mannitol usage should be monitored since inappropriate utilization of the substance could conversely have negative effects on CE patients. CE is thought to be related to bloodbrain barrier dysfunction. Nonetheless, a fluid clearance mechanism called the glial-lymphatic or glymphatic system was updated. This pathway facilitates the transport of cerebrospinal fluid (CSF) into the brain along arterial perivascular spaces and later into the brain interstitium. After removing solutes from the neuropil into meningeal and cervical lymphatic drainage arteries, the route then directs flows into the venous perivascular and perineuronal regions. Remarkably, the dual function of the glymphatic system was observed to protect the brain from further exacerbated damage. From our point of view, future studies ought to concentrate on the management of CE based on numerous targets of the updated glymphatic system. Further clinical trials are encouraged to apply these agents to the clinic as soon as possible.