3-N-butylphthalide (NBP) comprises one of the chemical constituents of celery oil. It has a series of pharmacological mechanisms including reconstructing microcirculation, protecting mitochondrial function, inhibiting oxidative stress, and inhibiting neuronal apoptosis and etc. Based on the complex multi-targets of pharmacological mechanisms of NBP, the clinical application of NBP is increasing and dried clinical researches and animal experiments are also focused on NBP. The aim of this review was to comprehensively and systematically summarize the application of NBP on neurological diseases and briefly summarize its application to non-neurological diseases. Moreover, recent progress in experimental models of NBP on animals was summarized. Literature was collected from Pubmed until November 2018,using the search terms including “3-N-butylphthalide”, “microcirculation”, “mitochondria”, “ischemic stroke”, “Alzheimer's disease”, “vascular dementia”, “Parkinson's disease”, “brain edema”, “CO poisoning”, “traumatic central nervous system injury”, “autoimmune disease”, “amyotrophic lateral sclerosis”, “seizures”, “diabetes”, “diabetic cataract”, and “atherosclerosis”. Literature was derived from English articles or articles that could be obtained from English abstracts. Article type was not limited. References were also identified from the bibliographies of identified articles and the authors’ files. NBP has become an important adjunct for ischemic stroke. In vascular dementia, the clinical application of NBP to treat severe cognitive dysfunction syndrome caused by the hypoperfusion of brain tissue during cerebrovascular disease is also increasing. Evidence also suggests that NBP has a therapeutic effect for neurodegenerative diseases. Many animal experiments have found that it can also improve symptoms in other neurological diseases such as epilepsy, cerebral edema, and decreased cognitive function caused by severe acute carbon monoxide poisoning. Moreover, NBP has therapeutic effects for diabetes, diabetes-induced cataracts, and non-neurological diseases such as atherosclerosis. Mechanistically, NBP mainly improves microcirculation and protects mitochondria. Its broad pharmacological effects also include inhibiting oxidative stress, nerve cell apoptosis, inflammatory responses, and anti-platelet and anti-thrombotic effects. The varied pharmacological mechanisms of NBP involve many complex molecular mechanisms; however, there many unknown pharmacological effects await further study. This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0

Toll-like receptors (TLRs) are important initiators of the immune response, both innate and acquired. Evidence suggests that gene polymorphisms within TLRs cause malfunctions of certain key TLR-related signaling pathways, which subsequently increases the risk of autoimmune diseases. We illustrate and discuss the current findings on the role of Toll-like receptor gene polymorphisms in numerous autoimmune diseases in this review, such as type 1 diabetes mellitus, Graves’ disease, rheumatoid arthritis, systemic lupus erythematosus and multiple sclerosis. The study of genetic variation in TLRs in different populations has shown a complex interaction between immunity and environmental factors. This interaction suggests that TLR polymorphisms affect the susceptibility to autoimmune diseases differently in various populations. The identification of Toll-like receptor gene polymorphisms can expand our understanding of the pathogenesis of autoimmune diseases, which will subsequently guide effective medical management and provide insight into prognosis and advanced treatments.

Background and Objectives: The Clinical Assessment Scale in Autoimmune Encephalitis (CASE) is a scale for assessing severity in autoimmune encephalitis. We aimed to validate the CASE score in a Chinese population and evaluate its clinical significance. Methods: Patients diagnosed with autoimmune encephalitis were recruited between June 2014 and May 2019 from two hospitals. CASE and modified Rankin Scale (mRS) scores were obtained. Data regarding clinical features, treatment, and available information were gathered from the hospital information system. Results: Of the 176 patients with autoimmune encephalitis, 11 died and 14 had tumors. Ten patients received second-line treatment. The CASE scores of patients receiving second-line treatment were significantly higher (median CASE: 15) than in those receiving first-line treatment (median CASE: 8) (p2). Areas under the curve of CASE on whether functional status was poor at 1 year were 0.89 (p<0.001). Sixty patients were admitted to the intensive care unit (ICU), and the CASE scores were positively correlated with days in the ICU (r=0.58, p0.05). Additionally, the CASE scores were positively associated with the mRS scores (r=0.85 p<0.001). Conclusions: The CASE score is suitable for the comprehensive assessment of Chinese patients with autoimmune encephalitis, which may help clinicians to select the appropriate intervention and estimate the disease severity and prognosis.

Herpes simplex encephalitis (HSE) caused by herpes simplex virus 1 (HSV-1) infection can lead to a high mortality rate and severe neurological sequelae. The destruction of the blood-brain barrier (BBB) is an important pathological mechanism for the development of HSE. However, the specific mechanism underlying the BBB destruction remains unclear. Our previous study found that the Golgi apparatus (GA) plays a crucial role in maintaining the integrity of the BBB. Therefore, this present study aimed to investigate the role of the GA in the destruction of the BBB and its underlying mechanisms. Mouse brain endothelial cells (Bend.3) were cultured to establish a BBB model in vitro, and then infected with HSV-1. The results showed that HSV-1 infection caused downregulation of the Golgi-associated protein GM130, accompanied by Golgi fragmentation, cell apoptosis, and downregulation of tight junction proteins occludin and claudin 5. Knockdown of GM130 with small interfering RNA in uninfected Bend.3 cells triggered Golgi fragmentation, apoptosis, and downregulation of occludin and claudin 5. However, overexpression of GM130 in HSV-1 infected Bend.3 cells by transient transfection partially attenuated the aforementioned damage caused by HSV-1 infection. When the pan-caspase inhibitor Z-VAD-fmk was used after HSV-1 infection to inhibit apoptosis, the protein levels of GM130, occludin and claudin 5 were partially restored. Taken together, these observations indicate that HSV-1 infection of Bend.3 cells triggers a GM130-mediated Golgi stress response that is involved in apoptosis, which in turn results in downregulation of occludin and claudin 5 protein levels. Meanwhile, GM130 downregulation is partially due to apoptosis triggered by HSV-1 infection. Our findings reveal an association between the GA and the BBB during HSV-1 infection and identify potentially novel targets for protecting the BBB and therapeutic approaches for patients with HSE.

Background and purpose: The incidence and prevalence of autoimmune encephalitis is gradually increasing. This retrospective observational study primarily aimed to analyze the clinical characteristics of autoimmune encephalitis patients in the Second Xiangya Hospital and report patient prognoses after immunotherapy. Methods: The clinical data of 86 patients who were diagnosed with autoimmune encephalitis from October 2014 to September 2018 were collected, and their corresponding clinical characteristics, laboratory examination, treatment, and outcome data analyzed. Results: In our study, 72 patients (83.7%) were positive for anti-NMDAR (N-methyl-D-aspartate receptor) antibody; 5 patients (6%) for anti-GABABR (γ-aminobutyric acid receptor-A) ; 4 patients (4.7%) for anti-LGI1 (leucine-rich, glioma inactivated 1); 3 patients (3.5%) for anti-Caspr2 (contactin-associated protein-like 2) (1 patient was positive for both anti-LGI1 and anti-Caspr2 antibodies); and 3 patients (3.5%) for onconeural antibodies. Among the 86 patients diagnosed as having autoimmune encephalitis, 50% showed acute disease onset (≤2 weeks). The most common inducing factor was fever or cold (17/86, 19.8%). The main clinical symptoms included, among others, psychiatric disturbances (82.5%), epilepsy (60.5%), autonomic dysfunction (58.1%), sleep disorders (45.3%), consciousness disorders (45.3%), and speech disorders (46.5%). No significant correlation between ICU admission rates and CSF or serum antibody scores was observed. However, CSF antibody scores of (+++) and (++) were associated with longer lengths of hospitalization (p < 0.05) and a higher CSF WBC count when compared with CSF antibody scores of (+) in patients with anti-NMDAR encephalitis (p < 0.05). Additionally, there was no significant correlation between mRS score difference on admission and discharge (after immunotherapy) and age, sex, and choice of immune treatment, while immune therapy taken within 15 days from onset was more inclined to be associated with an mRS score difference≥2 after immunotherapy in patients with anti-NMDAR encephalitis (p = 0.006). Conclusions: Autoimmune encephalitis has an acute or sub-acute onset and presents with psychotic symptoms, epilepsy, and autonomic dysfunction. The sex ratio in anti-NMDAR encephalitis was nearly balanced. Infection was a major factor inducing anti-NMDAR encephalitis, and the CSF antibody scores could be helpful in determining its prognosis since these scores showed associations with hospitalization duration and CSF WBC counts.