The Etiology of Intracranial Artery Stenosis in Autoimmune Rheumatic Diseases-An Observational High-Resolution Magnetic Resonance Imaging Study.

BACKGROUND AND PURPOSE: Autoimmune rheumatic diseases (AIRD) can cause intracranial artery stenosis (ICAS) and lead to stroke. This study aimed to characterize patients with ICAS associated with AIRD. MATERIALS AND METHODS: Utilizing data from a high-resolution magnetic resonance imaging (HRMRI) database, we retrospectively reviewed AIRD patients with ICAS. Stratification into vasculitis, atherosclerosis, and mixed athero-vasculitis subtypes was based on imaging findings, followed by a comparative analysis of clinical characteristics and outcomes across these subgroups. RESULTS: Among 139 patients (45.1±17.3 years; 64.7% females), 56 (40.3%) were identified with vasculitis, 57 (41.0%) with atherosclerosis, and 26 (18.7%) with mixed athero-vasculitis. The average interval from AIRD-onset to HRMRI was 5 years. Patients with vasculitis presented with a younger age of AIRD-onset (34.5±19.4 years), nearly ten years earlier than other groups (P=0.010), with a higher artery occlusion incidence (44.6% vs. 21.1% and 26.9%, P=0.021). Patients with atherosclerosis showed the highest cardiovascular risk factor prevalence (73.7% vs. 48.2% and 61.5%, P=0.021) but lower intracranial artery wall enhancement instances (63.2% vs. 100% in others, P<0.001). The mixed athero-vasculitis group, predominantly male (69.2% vs. 30.4% and 25.6%, P<0.001), exhibited the most arterial involvement (5 arteries per person vs. 3 and 2, P=0.001). Over an average 21-month follow-up, 23 (17.0%) patients experienced stroke events, and 8 (5.9%) died, with the mixed athero-vasculitis group facing the highest risk of stroke events (32.0%) and the highest mortality (12.0%). CONCLUSIONS: Intracranial arteries are injured and lead to heterogeneous disease courses when exposed to AIRD and cardiovascular risk factors. While atherosclerosis acceleration is common, vasculitis may further contribute to early-developed occlusion and multiple artery involvement. Varied intracranial arteriopathies may result in different outcomes. ABBREVIATIONS: ICAS = intracranial artery stenosis; AIRD = Autoimmune rheumatic diseases; HRMRI = high-resolution magnetic resonance imaging.

Transcription Factor EB: A Promising Therapeutic Target for Ischemic Stroke.

Transcription factor EB (TFEB) is an important endogenous defensive protein that responds to ischemic stimuli. Acute ischemic stroke is a growing concern due to its high morbidity and mortality. Most survivors suffer from disabilities such as numbness or weakness in an arm or leg, facial droop, difficulty speaking or understanding speech, confusion, impaired balance or coordination, or loss of vision. Although TFEB plays a neuroprotective role, its potential effect on ischemic stroke remains unclear. This article describes the basic structure, regulation of transcriptional activity, and biological roles of TFEB relevant to ischemic stroke. Additionally, we explore the effects of TFEB on the various pathological processes underlying ischemic stroke and current therapeutic approaches. The information compiled here may inform clinical and basic studies on TFEB, which may be an effective therapeutic drug target for ischemic stroke.

Cellular Prion Protein Attenuates OGD/R-Induced Damage by Skewing Microglia toward an Anti-inflammatory State via Enhanced and Prolonged Activation of Autophagy.

Modulation of microglial pro/anti-inflammatory states and autophagy are promising new therapies for ischemic stroke, but the underlying mechanisms remain largely unexplored. The objective of the study is to determine the intrinsic role of PrPC (cellular prion protein) in the regulation of microglial inflammatory states and autophagy in ischemic stroke. PrPC was expressed in murine microglia, and an in vitro oxygen-glucose deprivation/reperfusion (OGD/R) model was established in microglia of different PRNP genotypes. During reperfusion following OGD, wild-type (WT) microglia had significantly increased pro/anti-inflammatory microglial percentages and related cytokine [interleukin [IL]-6, IL-10, IL-4, tumor necrosis factor, and interferon-gamma] release at reperfusion after 48 or 72 h. WT microglia also showed greater accumulation of the autophagy markers LC3B-II/I (microtubule-associated protein B-light chain 3), but not of p62 or LAMP1 (lysosome-associated membrane protein) at reperfusion after 24 h and 48 h. Inhibition of autophagy using 3-methyladenine or bafilomycin A1 aggravated the OGD/R-induced pro-inflammatory state, and the effect of 3-methyladenine was significantly stronger than that of bafilomycin A1. Concomitantly, PRNP knockout shortened the accumulation of LC3B-II/I, suppressed microglial anti-inflammatory states, and further aggravated the pro-inflammatory states. Conversely, PRNP overexpression had the opposite effects. Bafilomycin A1 reversed the effect of PrPC on microglial inflammatory state transformation. Moreover, microglia with PRNP overexpression exhibited higher levels of LAMP1 expression in the control and OGD/R groups and delayed the OGD/R-induced decrease of LAMP1 to reperfusion after 48 h. PrPC attenuates OGD/R-induced damage by skewing microglia toward an anti-inflammatory state via enhanced and prolonged activation of autophagy.

The Role of Cellular Prion Protein in Cancer Biology: A Potential Therapeutic Target.

Prion protein has two isoforms including cellular prion protein (PrPC) and scrapie prion protein (PrPSc). PrPSc is the pathological aggregated form of prion protein and it plays an important role in neurodegenerative diseases. PrPC is a glycosylphosphatidylinositol (GPI)-anchored protein that can attach to a membrane. Its expression begins at embryogenesis and reaches the highest level in adulthood. PrPC is expressed in the neurons of the nervous system as well as other peripheral organs. Studies in recent years have disclosed the involvement of PrPC in various aspects of cancer biology. In this review, we provide an overview of the current understanding of the roles of PrPC in proliferation, cell survival, invasion/metastasis, and stem cells of cancer cells, as well as its role as a potential therapeutic target.

Microbiota-Gut-Brain Axis and Epilepsy: A Review on Mechanisms and Potential Therapeutics.

The gut-brain axis refers to the bidirectional communication between the gut and brain, and regulates intestinal homeostasis and the central nervous system via neural networks and neuroendocrine, immune, and inflammatory pathways. The development of sequencing technology has evidenced the key regulatory role of the gut microbiota in several neurological disorders, including Parkinson's disease, Alzheimer's disease, and multiple sclerosis. Epilepsy is a complex disease with multiple risk factors that affect more than 50 million people worldwide; nearly 30% of patients with epilepsy cannot be controlled with drugs. Interestingly, patients with inflammatory bowel disease are more susceptible to epilepsy, and a ketogenic diet is an effective treatment for patients with intractable epilepsy. Based on these clinical facts, the role of the microbiome and the gut-brain axis in epilepsy cannot be ignored. In this review, we discuss the relationship between the gut microbiota and epilepsy, summarize the possible pathogenic mechanisms of epilepsy from the perspective of the microbiota gut-brain axis, and discuss novel therapies targeting the gut microbiota. A better understanding of the role of the microbiota in the gut-brain axis, especially the intestinal one, would help investigate the mechanism, diagnosis, prognosis evaluation, and treatment of intractable epilepsy.

AQP4-IgG positive paraneoplastic NMOSD: A case report and review.

INTRODUCTION: Neuromyelitis optica spectrum disorder (NMOSD; also known as Devic syndrome) is a clinical syndrome of central nervous system characterized by immune mediated attacks of acute optic neuritis and myelitis. Paraneoplastic neurological syndrome is a group of nervous system disorders resulting from the remote immune effects of malignant neoplasm. NMOSD occurs mostly in young people, and tumor is not a common cause, especially recurrent tumor. METHODS: We reported a case of a 59-year-old man who developed anti-aquaporin-4 IgG positive longitudinally extensive myelitis. We also summarized and analyzed previously reported cases of paraneoplastic NMOSD. RESULTS: Among these 43 patients, 88.4% patients are female. The largest number of patients is between 60 and 69 years old. Breast cancer and lung cancer are the most common types. The most common lesions were located in the cervicothoracic region with patchy gadolinium enhancement. The existing treatment can only delay rather than stop the progress of the disease. CONCLUSION: It is necessary to perform tumor screening in patients with NMOSD, especially patients over 50 years.

Myelin Oligodendrocyte Glycoprotein Antibody Associated Cerebral Cortical Encephalitis: Case Reports and Review of Literature.

Myelin oligodendrocyte glycoprotein antibody-associated disease is an immune-mediated demyelinating disease of the central nervous system that is present in both adults and children. The most common clinical manifestations are optic neuritis, myelitis, acute disseminated encephalomyelitis, and brainstem syndrome. Cerebral cortical encephalitis (CCE) is a rare clinical phenotype of myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD), which usually begins with seizures, headaches, and fever, and may be misdiagnosed as viral encephalitis in the early stages. Herein, we report two typical MOG antibody (MOG-Ab)-positive patients presenting with CCE, both of whom presented with headache, fever, seizures, and who recovered completely after immunotherapy. In addition, we performed a systematic review of the present literature from the perspectives of population characteristics, clinical symptoms, MRI abnormalities, treatments, and prognosis. Among the patients reported in 25 articles, 33 met our inclusion criteria, with the age of onset ranging from 4 to 52 years. Most of the patients had seizures, headache, fever, and unilateral cortical lesions on brain MRI. For acute CCE, 30 patients were treated with high-dose intravenous methylprednisolone, and the symptoms of most patients were completely relieved after immunotherapy. This study reported our experience and lessons learned in the diagnosis and treatment of MOG-Ab-positive CCE and provides a systematic review of the literature to analyse this rare clinical phenotype.