Neuroimmunomodulation最新文献

Background: Traumatic brain injury (TBI) is posing serious health challenges for people across the globe due to high morbidity and mortality. However, none of the agents prevents or limits the damage caused by TBI because of its multifactorial etiology. Thus, the discovery of novel agents which can act via several pathways could serve the purpose and afford favorable consequence against TBI. Therefore, in the present article, we intended to investigate the protective effect of rhamnazin (RMZ), a dimethoxyflavone against experimentally induced TBI in mice.

Methods: The effect of RMZ was investigated on cerebral edema and grip test score after induction of experimental brain injury in rats. The effect of RMZ was also investigated on neuronal degeneration in brain tissues of the experimental mice via Nissl staining and flow cytometry analysis. The expression of Bax and Bcl-2 was also quantified using Western blot analysis. The level of inflammatory cytokines (TNF-α and IL-1β) and oxidative stress markers (malondialdehyde, superoxide dismutase, and glutathione peroxidase) was also determined using enzyme-linked immunosorbent assay.

Results: RMZ showed a significant reduction in edema and improved grip strength. It also prevented neuronal degeneration via inhibition of neuronal apoptosis as shown by flow cytometry analysis. RMZ showed an antiapoptotic effect via reduction of Bax and increased the expression of Bcl-2 in Western blot analysis. It also showed to inhibit oxidative stress and inflammation compared to the TBI group.

Conclusion: Collectively, our study is first to demonstrate the protective effect of RMZ against experimentally induced TBI in rats.

Introduction: Prolactin (PRL) exerts inflammatory and anti-inflammatory properties and is also thought to play an important role in the pathogenesis of neurodegenerative diseases (NDs). However, serum PRL levels in patients with NDs were inconsistent in the research literature.

Objective: We aimed to assess the serum PRL levels in patients with NDs.

Methods: Electronic databases, including MEDLINE, Embase, Cochrane Library database, clinicaltrials.gov, Web of Science, and Google Scholar, and reference lists of articles were searched up to December 31, 2020. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by fixed-effect or random-effect model analysis.

Results: A total of 36 comparisons out of 29 studies (3 RCTs and 26 case controls) focusing on NDs (including Parkinson's disease, Alzheimer's disease, Huntington's disease [HD], multiple sclerosis [MS], and epilepsy) were reported. The meta-analysis showed that there was no statistically significant difference in serum PRL levels between patients with NDs and healthy controls (SMD = 0.40, 95% CI: -0.16 to 0.96, p = 0.16). Subgroup analysis showed that serum PRL levels in patients with HD and MS were higher than those of healthy controls. Furthermore, patients with NDs aged <45 years had higher serum PRL levels (SMD = 0.97, 95% CI: 0.16-1.78, p = 0.018) than healthy controls. High serum PRL levels were found in subgroups such as the microenzymatic method, Asia, and the Americas.

Conclusions: Our meta-analysis showed serum PRL levels in patients with HD and MS were significantly higher than those in healthy controls. Serum PRL levels were associated with age, region, and detection method. Other larger sample studies using more uniform detection methods are necessary to confirm our results.

Introduction: Physical exercise is an important component of managing Alzheimer's disease (AD). miRNAs can be modulated by exercise intervention.

Objective: The study explored the involvement and potential mechanism of miR-192-5p in the protective effect of physical exercise on AD.

Methods: Ninety AD patients were enrolled, in which 45 cases accepted cycling training for continuous 3 months. The expression changes of miR-192-5p before and after exercise were analyzed by reverse transcription-quantitative PCR. 8-month-old APP/PS1 double Tg mice were used as the AD animal model. Mice in the voluntary exercise (VE) group received VE for 4 weeks. Morris water maze (MWM) test was used to evaluate the learning and memory function. Enzyme-linked immunosorbent assay was used to calculate the level of IL-1β, IL-6, and TNF-α.

Results: AD patients showed elevated MMSE scores, decreased ADAS-cog and NPI-Q scores after 3 months of exercise. miR-192-5p was downregulated in the serum of AD patients and correlated with the levels of MMSE score, ADAS-cog, and NPI-Q score. A positive association was detected between serum miR-192-5p with TNF-α, IL-6, and IL-1β levels. MiR-192-5p is downregulated in the hippocampus tissues of mice after VE. Overexpression of miR-192-5p reversed the neuroprotective effect of exercise on AD in mice and promoted the inflammatory response of AD mice.

Conclusion: MiR-192-5p can be modulated by the exercise intervention and involved in the protective effect of exercise on AD.

Objective: The vagus nerve constitutes the main component of the parasympathetic nervous system and plays an important role in the regulation of neuro-immune responses. Invasive stimulation of the vagus nerve produces anti-inflammatory effects; however, data on humoral immune responses of transcutaneous vagus nerve stimulation (tVNS) are rare. Therefore, the present study investigated changes in serum cytokine concentrations of interleukin-1β (IL-1β), IL-6, IL-8, and tumor necrosis factor α (TNFα) following a short-term, non-invasive stimulation of the vagus nerve.

Methods: Whole blood samples were collected before and after a short-lived application of active tVNS at the inner tragus as well as sham stimulation of the earlobe. Cytokine serum concentrations were determined in two healthy cohorts of younger (n = 20) and older participants (n = 19). Differences between active and sham conditions were analyzed using linear mixed models and post hoc F tests after applying Yeo-Johnson power transformations. This trial was part of a larger study registered on ClinicalTrials.gov (NCT05007743).

Results: In the young cohort, IL-6 and IL-1β concentrations were significantly increased after active stimulation, whereas they were slightly decreased after sham stimulation (IL-6: p = 0.012; IL-1β: p = 0.012). Likewise, in the older cohort, IL-1β and IL-8 concentrations were significantly elevated after active stimulation and reduced after sham application (IL-8: p = 0.007; IL-1β: p = 0.001). In contrast, circulating TNFα concentrations did not change significantly in either group.

Conclusion: Our results show that active tVNS led to an immediate increase in the serum concentrations of certain pro-inflammatory cytokines such as IL-1β, IL-6, and/or IL-8 in two independent cohorts of healthy study participants.

Background: Ischemic stroke is a major health issue that causes high incidents of morbidity and mortality worldwide. Irisin is an excise-induced protein that has exhibited pleiotropic properties. Accumulating evidence reveals its critical roles in the regulation of various cellular functions, including nervous system functions. This study aims to disclose the effect of irisin on rat cerebral neurons suffering from hypoxia/reoxygenation (H/R) treatment and to explore the potential underlying molecular mechanisms.

Methods: The percentage of rat cerebral neuron cell death was determined by flow cytometry analysis and MTT assay. The expression levels of target genes were measured by western blotting and real-time quantitative reverse transcription PCR assay.

Results: Our results demonstrated that irisin treatment substantially reduced H/R-induced apoptosis of rat cerebral neurons. Further investigation revealed that irisin treatment markedly decreased mitogen-activated protein kinase (MAPK) signaling pathway activation and suppressed pro-informatory cytokine expression in cerebral neurons with H/R challenge. Finally, we showed that the neuroprotective effect and anti-inflammatory effect of irisin were comparable with three MAPK signaling inhibitors.

Conclusion: Irisin exerts profound neuroprotective and anti-inflammatory effects on H/R-stimulated cerebral neurons by inhibiting the MAPK signaling activation. Therefore, irisin may serve as a potential drug for the treatment of patients with ischemic stroke.

Purpose: We report two cases diagnosed as acute necrotizing encephalopathy (ANE) with acute onset and various clinical manifestations.

Methods: The patients' data were obtained from the medical records of the Binzhou Medical University Hospital in Binzhou, China. The clinical symptoms, laboratory examination, neuroimaging, treatment, and prognosis of the 2 patients were collected and analyzed.

Results: We report 2 adult ANE patients with acute onset. The first symptom was fever, followed by symptoms and signs of damage to the central nervous system. The patients were infected with herpes simplex virus and influenza virus, respectively. The main manifestation on brain magnetic resonance imaging was a mixed-signal of a "three-layer structure" in the bilateral thalamus. The first patient died. Based on the experience of the diagnosis and treatment of the first patient, combined with a review of the literature, the second patient was immediately treated with glucocorticoid pulse therapy combined with gamma globulin injection. This patient's condition was controlled, and the prognosis was good.

Conclusions: This study describes the clinical symptoms, laboratory examination, neuroimaging evidence, and treatment experience of ANE in adults. We believe that the progress of the disease may be controlled, and the prognosis may be improved if glucocorticoid pulse therapy combined with gamma globulin injection is used as soon as possible.

Many coronavirus disease 2019 (COVID-19)-recovered patients report signs and symptoms and are experiencing neurological, psychiatric, and cognitive problems. However, the exact prevalence and outcome of cognitive sequelae is unclear. Even though the severe acute respiratory syndrome coronavirus 2 has target brain cells through binding to angiotensin-converting enzyme 2 (ACE2) receptor in acute infection, several studies indicate the absence of the virus in the brain of many COVID-19 patients who developed neurological disorders. Thus, the COVID-19 mechanisms for stimulating cognitive dysfunction may include neuroinflammation, which is mediated by a sustained systemic inflammation, a disrupted brain barrier, and severe glial reactiveness, especially within the limbic system. This review explores the interplay of infected lungs and brain in COVID-19 and its impact on the cognitive function.

Introduction: Thyroid-stimulating hormone receptor (TSHR) is widely expressed in human tissues and cells. TSHR is not only involved in thyroid disease but also in the neuroendocrine-immune regulatory network. However, no study has exclusively focused on the expression and function of TSHR in natural killer (NK) cells.

Methods: We studied TSHR expression using reverse transcription PCR to verify TSHR mRNA transcripts in human and mouse NK cells. Human and mouse thyroid and liver tissues as well as peripheral blood mononuclear cells (PBMCs) or spleen lymphoid cells (SLCs) were used as controls. The TSHR protein levels in NK-92 cells were determined by immunofluorescence staining. The function of TSHR in NK cells was investigated by measuring the TSH-stimulated cAMP levels.

Results: TSHR mRNA was detected in human and mouse NK cells as well as in NK-92 cells and had the same sequence as that of thyroid-derived, PBMC-derived, and liver-derived mRNA. The TSHR protein was also expressed in the cell membrane of NK-92 cells. Furthermore, the cAMP levels in NK-92 cells were significantly higher after adding 102 mIU/mL of bovine TSH at p < 0.05, which stimulated cAMP production in NK-92 cells.

Conclusions: Our findings confirm that TSHR is present and functional in NK cells and provide key clues for the potential regulatory effects of TSH on TSHR in NK cells in the immune system.