Journal of neuroimmunology最新文献

Background and objectives: Guhong injection (GHI) has multiple components and generates diverse effects, and is mainly used in the treatment of acute ischemic stroke (AIS). The purpose of this study is to explore the multiple effects of GHI in AIS models in mice and the mechanism how they work together to affect the stroke outcome.

Methods: Middle cerebral artery occlusion (MCAO) and photothrombotic stroke models were established with GHI or vehicle. Neurological function assessment including the Modified Neurological Severity Score (mNSS) and rota-rod test, and relative cerebral blood flow were monitored at day 1 and day 3 after model establishment. Flow cytometry, 2, 3, 5-Triphenyltetrazolium chloride (TTC) staining, histology and immunofluorescence, Western blotting (WB) assay were performed at day 3.

Results: The mean mNSS score was lower and the latency to falling off the rota-rod was prolonged at day 3 in the GHI group. GHI reduced the relative infarct volume and increased the relative cerebral blood flow. The histopathological damage of ischemic core was significantly ameliorated in the GHI group. GHI decreased the Caspase-3⁺ cells and increased the MAP-2⁺ and Claudin-5⁺ cells. GHI increased the expression of Bcl-2 and the ratio of Bcl-2/Bax, and decreased the expression levels of Bax, Caspase-3 and Cleaved-Caspased-3. GHI reduced the microglia, decreased the IL-6 positive cells, TNF-α positive cells and increased TGF-β1 positive cells.

Conclusions: GHI alleviated brain injury and neurological deficits through improving cerebral blood circulation, attenuating neuronal apoptosis, reducing the disruption of blood-brain barrier (BBB) and decreasing neuroinflammation in MCAO and photothrombotic stroke models in mice. GHI has certain neuroprotective function to be applied to clinical use.

This study explores the nuanced immunomodulatory effects of sertraline, which is widely used in the treatment of major depression, obsessive-compulsive disorder, and anxiety in adults and children. Recent investigations have emphasized the intricate interplay between depression and the body's inflammatory response. This has sparked an exploration into the impact of sertraline on the immune system, an area that still awaits comprehensive exploration. Our research methodically examines the influence of sertraline on the levels of cytokines (TNF-a, IL-6, IL-12p40, GM-CSF) in the macrophage cell line J774.2. This analysis is conducted under conditions with and without the lipopolysaccharide (LPS) danger signal. To enhance specificity, sertraline's effects are juxtaposed with those of salicylic acid, a known anti-inflammatory agent. Furthermore, a comprehensive exploration of sertraline's impact on the intracellular signaling pathways regulated phosphoinositide-3-kinase (PI3K) and the p38 pathway is the third major signaling cassettes of the mitogen-activated protein kinase (MAPK) signaling is presented. The outcomes of our study unveil distinctive patterns in sertraline's modulation of cytokine levels within macrophage cells. Under the influence of the LPS danger signal, sertraline exhibits immunostimulatory characteristics, contrasting with its ability to suppress GM-CSF cytokine levels, even in the presence of LPS. Notably, the p38 pathway portrays a pro-inflammatory role for sertraline, while inhibiting the PI3K signaling pathway highlights its anti-inflammatory attributes. These findings contribute novel insights into the intricate interplay between sertraline and the immune system.

This review intends to gather literature to provide a comprehensive understanding of the molecular mechanisms and role of T follicular helper cells (Tfh) in the interaction with germinal centers (GCs) in Myasthenia Gravis (MG) disease regarding new developments focusing on Tfh as a therapeutic target and its key regulator B cell lymphoma 6 (Bcl6). Tfh cells are CD4+ T cells specialized in providing signals for the activation and maturation of B cells plus the formation and maintenance of GCs; the role of Bcl6 stands as the key transcriptional factor for the survival of GCs and promotion of Tfh generation. Previous studies have demonstrated gene therapy to be beneficial by achieving re-establishment of "immune homeostasis" and amelioration of the proinflammatory process.

Background: The study assessed group differences in the thalamus microstructural parameters among healthy individuals and relapsing-remitting multiple sclerosis (RRMS) patients and examined the relationship between quantitative MRI (qMRI) parameters and neurological scores, T2 lesion load, and serum neurofilament light chain (sNfL) levels.

Methods: A total of 30 patients with RRMS and 26 age- and sex-matched healthy controls were recruited in this study. The qMRI images were obtained from these individuals. T2 lesion load, thalamic volume, and parameters of thalamic subnuclei were estimated. The neurological functions of participants were assessed using a battery of tests. sNfL concentrations were measured using the single molecule array (SIMOA) technique.

Results: T2 relaxometry in the whole thalamus and its subnuclei were increased, and showed an apparent correlation with T2 lesion load and the severity of MS (EDSS, MSSS, 9HPT, T25FW, SDMT). T1 variability was prolonged in most thalamic subnuclei, and it was correlated with the severity of MS (EDSS, 9HPT, SDMT). Thalamic volumetric parameters of MS patients were smaller than those of healthy controls (p < 0.001) and showed an apparent correlation with MS severity. Surprisingly, sNfL levels showed no correlation with T2 relaxometry, T1 variability, or thalamic volumetric parameters.

Conclusion: Quantitative synthetic MRI, especially, the metric T2 relaxation times provides a surrogate parameter for assessing underlying thalamic and subnuclei damage in the RRMS group. Integrating structural and quantitative MRI allows a better assessment of the neurodegeneration in the normal-appearing thalamus of RRMS.

Many forms of autoimmune encephalitis are mediated by neuronal cell-surface directed autoantibodies. The co-occurrence of four neuronal cell-surface antibodies in a single patient is exceptionally rare. We report a patient who had a severe encephalitis associated with antibodies to NMDA, Glycine, GABA_A and GABA_B receptors. Case: A 28-year-old man on tacrolimus presented with a first seizure. Thereafter, he developed confusion, cerebellar signs, opsoclonus, neuromyotonia and medication-refractory seizures. CSF sampling revealed 826 white cells and NMDA, glycine and GABA_B receptor antibodies: all were also detected in serum along with additional GABA_A receptor antibodies. Neural antibodies were detected using fixed (NMDA, GABA_A, GABA_B receptor) or live (glycine receptor) cell-based assays at Oxford Neuroimmunology Laboratory, Oxford, UK. MRI brain demonstrated cerebellar leptomeningeal enhancement and a hyperintense lesion in the cerebellar vermis. EEG revealed extreme delta brush and needle EMG confirmed neuromyotonia. No underlying malignancy was detected. Methylprednisolone, IVIG, Rituximab, therapeutic plasma exchange, cyclophosphamide and bortezomib were administered sequentially, with minimal clinical improvement. Death secondary to respiratory sepsis occurred on the 714th hospital day. Postmortem revealed pan-cerebellar atrophy with Purkinje cell loss; dentate nucleus ganglionopathy, and thoracolumbar cord myelopathy. In summary, the detection of multiple neuronal cell-surface antibodies in autoimmune encephalitis is unusual and may result in a complex overlap syndrome with a poor response to immunotherapy.

In multiple sclerosis (MS) the B cell depleting drug ocrelizumab has shown high efficacy in reducing inflammatory activity. Its mechanism of action is unclear due to B cell subset complexity and unknown roles in pathogenesis. Here, we comprehensively phenotyped and quantitated peripheral blood B cell subsets before and after ocrelizumab infusion to gain insight into the fate of B cell subsets with pathogenic potential. Peripheral blood B cells were collected from treatment naïve patients at baseline and months one, three, and six following the first course of ocrelizumab treatment; at 6 months following the second treatment cycle; ∼14 months following their last infusion; and from healthy controls. Flow cytometry combined with cluster analysis was used to track depletion and repletion of naïve, memory, and antibody secreting cells. By month one, naïve B cells were depleted, but a small subset of memory B cells were retained with no depletion of antibody secreting cells. Uniform manifold approximation and projection for dimension reduction analysis of flow cytometry data revealed two non-class switched naïve clusters and two class switched memory clusters. One class switched cluster was activated in MS patients but largely absent in healthy controls. Both memory B cell subsets underwent depletion after a single six-month course of ocrelizumab treatment after which their proportions were reset to heathy control levels. These observations suggest that activated class-switched memory B cells could serve as a biomarker of recent or ongoing MS disease activity to guide redosing.