Background and Objectives To characterize the clinical and neuroimaging phenotypes of patients with autoantibodies to γ-aminobutyric acid type A receptor (GABA_AR). Methods Ten patients with autoantibodies against GABA_AR from Huashan Hospital Autoimmune Encephalitis cohort were identified. We used MRI assessments and clinical examinations to summarize major clinical profile and visualize and quantify lesion distribution features. The relationship between clinical features, neuroimaging phenotypes, and topology of GABA_AR expression were further investigated. Results The median age at onset of 10 patients (8 male patients and 2 female patients) with anti-GABA_AR encephalitis was 41.5 years (range: 17–73 years). All patients had prominent seizures and multifocal spotted or confluent lesions involved in limbic, frontal, and temporal lobes on brain MRI. Bilateral but asymmetric lesions in cingulate gyri were observed in all patients. These involved lesions could change dynamically with immunotherapies and relapse. Distribution of patients9 brain MRI lesions was positively correlated with gene expression level of β3 subunit–containing GABA_AR (Spearman ρ = 0.864, p = 0.001), the main target of autoantibodies. According to topology of lesions, patients with anti-GABA_AR encephalitis could be classified into 2 clinical-radiological types: confluent type with bilateral confluent lesions involved in almost all limbic, frontal, and temporal lobes and spotted type with multiple scattered small-to-medium patchy lesions. Patients with confluent type exhibited worse clinical presentations and outcomes when compared with those with spotted type (maximum modified Rankin scale [mRS]: 5 [5–5] vs 3.5 [3–4], respectively, p = 0.008; follow-up mRS: 4 [2–6] vs 0.5 [0–1], respectively, p = 0.016). Discussion Anti-GABA_AR encephalitis has distinctive neuroimaging phenotype. Cingulate gyri were frequently involved in this disorder. The topology of lesions might be associated with the distribution of β3 subunit–containing GABA_AR and reflected patients9 disease severity and outcomes.

Urotensin II (UII) could increase blood pressure and heart rate via increased central reactive oxygen species (ROS) levels. We reported previously that hydrogen sulfide (H₂S) exerts an antihypertensive effect by suppressing ROS production. The aim of the current study is to further examine the effects of endogenous and exogenous H₂S on UII-induced cardiovascular effects by using an integrated physiology approach. We also use cell culture and molecular biological techniques to explore the inhibitory role of H₂S on UII-induced cardiovascular effects. In this study, we found that cystathionine-β-synthase (CBS), the main H₂S synthesizing enzyme in CNS, was expressed in neuronal cells of the rostral ventrolateral medulla (RVLM) area. Cellular distribution of CBS and urotensin II receptor (UT) in SH-SY5Y cells that are confirmed as glutamatergic were identified by immunofluorescent and Western blots assay. In Sprague–Dawley rats, administration of UII into the RVLM resulted in an increase in mean arterial pressure (MAP), heart rate (HR), ROS production, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, and phosphorylation of p47^phox, extracellular signal-regulated protein kinase (ERK)1/2 and p38MAPK, but not stress-activated protein kinase/Jun N-terminal kinase (SAPK/JNK). These effects of UII were attenuated by application into the RVLM of endogenous (L-cysteine, SAM) or exogenous (NaHS) H₂S. These results were confirmed in SH-SY5Y cells. UII-induced cardiovascular effects were also significantly abolished by pretreatment with microinjection of Tempol, Apocynin, SB203580, or PD98059 into the RVLM. Preincubated SH-SY5Y cells with Apocynin before administration of UII followed by Western blots assay showed that ROS is in the upstream of p38MAPK/ERK1/2. Ga_o activation assay in SH-SY5Y cells suggested that H₂S may exert an inhibitory role on UII-induced cardiovascular effects by inhibiting the activity of Gα_o. These results suggest that both endogenous and exogenous H₂S attenuate UII-induced cardiovascular effects via Gα_o-ROS-p38MAPK/ERK1/2 pathway.

Bacterial infection triggered excessive inflammatory responses, yet the mechanisms linking inflammatory activation to immunometabolic adaptation remained incompletely understood. The mitochondrial translocator protein (TSPO) has been implicated in inflammatory activation and cellular metabolism. This study aimed to investigate the role of TSPO in inflammation mediated by Toll-like receptor 4 (TLR4). Herein, we integrated transcriptomic data from the human peripheral blood dataset GSE72829, and single-cell transcriptomic profiles from the CELLxGENE platform with cellular mechanistic experiments in BV2 microglia and RAW264.7 macrophages. Transcriptomic analyses revealed that TSPO expression was markedly upregulated in patients with bacterial infection (n = 52) and exhibited diagnostic potential to distinguish bacterial infection from healthy controls (HCs, n = 16) and viral infection (n = 92). TSPO-correlated genes were enriched in Toll-like receptor (TLR) signaling, inflammatory response, and immunometabolic pathways. Mechanistically, TSPO interacted with TLR4 and selectively modulated TLR4-driven inflammatory activation. TSPO deficiency augmented lipopolysaccharide (LPS) induced tumor necrosis factor‑α (TNF-α) and interleukin‑6 (IL-6) secretion, accompanied by disrupted Ca²⁺ homeostasis, impaired cholesterol balance, and compensatory metabolic remodeling characterized by elevated L-lactate and sustained Adenosine triphosphate (ATP) levels. Collectively, these findings identified TSPO as an immunometabolic regulator bridging TLR4 signaling and metabolic adaptation during inflammatory activation. Besides, TSPO represented a promising biomarker and therapeutic target to limit exaggerated inflammatory responses.