Shang, Pei

Study objective: To characterize physiologic autonomic dysfunction in humans after chronic spinal cord injury (SCI) relative to uninjured controls and to identify autonomic correlates to neuroimmune deficits. Hypothesis: Individuals with greater autonomic dysfunction after SCI will have more pronounced immune dysfunction, which will be further influenced by sympathetically mediated increases in catecholamine levels. Methodology: Both uninjured controls and individuals with SCI completed a battery of autonomic physiology tests aimed at characterizing preservation of supralesional/sublesional sympathetic activation and global sympathetic inhibition. The autonomic testing battery included 3-minute hand and foot cold pressor tests, 3 Valsalva maneuvers with goal expiratory pressure of 30 mmHg, a novel bladder pressor test (5 minutes of sustained bladder pressure at 35 cmH20 with room temperature sterile water infusion), paced breathing at 0.25 Hz for heart rate/blood pressure variability, and successive doses of bolus intravenous phenylephrine (Oxford technique). A subset of individuals in both cohorts had baseline and cold pressor stressed levels of catecholamines/cortisol drawn and immunologic assessments. Peripheral blood mononuclear cells were extracted from this baseline sample and assessed with flow cytometry for cellular exhaustion markers (CD69, PD-1, TIGIT, TIM-3). Antigen recall response, with/without primed exposure of catecholamines was also completed to identify how sympathetic activation variably impacted functional immune performance with exposure to viral peptides. Data: n=35 uninjured controls; n=29 individuals with SCI Summary of Results: When compared to uninjured controls, individuals with SCI demonstrated significant autonomic dysfunction in all three domains, with decreased supralesional sympathetic activation (Valsalva pressure recovery time, p< 0.0001), abnormal sublesional sympathetic activation (increased bradycardia, p< 0.0001), and impaired sympathetic inhibition (larger dose/body-weight adjusted increase in mean arterial pressure, p=0.0006). As expected, autonomic dysfunction in those with SCI existed on a continuum, with some having largely normal autonomic regulation and others exhibiting profound deficits. Principal component analysis confirmed these three domains as the primary drivers of variability. Cellular exhaustion markers were increased in those with SCI, with positive correlation (R2=0.42) between degree of global autonomic dysfunction (Z-score over 2.0) and CD3+ CD8+ T-cell TIM-3 immunologic exhaustion markers. Antigen recall response was impaired in those with SCI and autonomic dysfunction on physiologic testing, with pronounced decrement in response when catecholamines were added (mean 57% of response lost in CD69 T-cells to Epstein-Barr virus antigen exposure, 53% lost to Flu antigen). Conclusions: In humans with SCI, early evidence supports that individuals have greater autonomic dysfunction and that this is correlated to increased immunologic deficits. Funding Sources: NIH K23HD102663, R01NS115126 This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Noninvasive brain stimulation techniques have emerged as a promising therapeutic option for various central nervous system demyelinating diseases. Demyelinating diseases represent a group of pathological conditions that impact the central or peripheral nervous system. They are characterized by damage to or loss of the myelin sheath surrounding nerve fibers. This damage to myelin sheaths disrupts nerve signal transmission, leading to a wide range of signs and symptoms associated with neurological impairment. Treatment for demyelinating diseases usually aligns with the specific underlying cause. Noninvasive brain stimulation techniques can affect neuronal electrical activity and glial cell function, suggesting a potential option for intervention. In this narrative review, we explore the potential of noninvasive brain stimulation techniques for the treatment of central nervous system demyelinating disorders. Noninvasive brain stimulation techniques, including transcranial magnetic stimulation, transcranial electrical stimulation, transcranial focused ultrasound stimulation, optogenetic stimulation, low-intensity pulsed ultrasound, and transcranial photobiomodulation, have been shown to potentially intervene in the treatment of demyelinating diseases by affecting the electrical activity of nerve cells and glial cell function. In addition, this review summarizes the applications and mechanisms of noninvasive brain stimulation techniques in the treatment of central nervous system demyelinating diseases and how these techniques promote myelin regeneration and improve disease prognosis. This review also summarizes research advances in noninvasive brain stimulation techniques for the treatment of multiple sclerosis, acute disseminated encephalomyelitis, progressive multifocal leukoencephalopathy, and neuromyelitis optical spectrum disorder. Noninvasive brain stimulation techniques can improve disease symptoms by promoting oligodendrocyte proliferation and differentiation, enhancing myelin regeneration, and modulating immune responses. Although noninvasive brain stimulation techniques have shown potential in the treatment of various neurological disorders, their use in treating demyelinating diseases remains challenging. For example, transcranial focused ultrasound stimulation is a relatively new noninvasive brain stimulation technique with the advantages of high spatial resolution and the ability to stimulate deep brain structures, but its safety and efficacy in clinical applications need to be further investigated. Optogenetic stimulation offers highly precise neuromodulation, but its feasibility in clinical practice is limited by technical and ethical constraints. Overall, noninvasive brain stimulation techniques have significant potential in the treatment of central nervous system demyelinating diseases, but further research is needed to optimize stimulation parameters, improve therapeutic efficacy, and gain insight into their mechanism of action. With the continuous development of technology and in-depth clinical trials, noninvasive brain stimulation techniques are expected to become an effective treatment for central nervous system demyelinating diseases and provide new therapeutic options for such patients.

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.