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Although 82% of the cerebrospinal fluid (CSF) is localized in the subarachnoid space, the function of the blood-arachnoid barrier (BAB) has not been elucidated. We found an abundance of drug efflux transporter proteins in the BAB. Moreover, several transporter proteins, including organic anion transporters and organic cation transporters have been found in the BAB. Significant in vivo transport activity of the BAB has been observed, suggesting that the BAB plays a pivotal role in the CNS barrier. Using quantitative targeted absolute proteomic analysis, we determined the similarities and differences in transport function and tight junction formation among the BBB, BAB, blood-CSF barrier (BCSFB), and blood-spinal cord barrier (BSCB). Furthermore, we proposed several hypotheses regarding the molecular mechanism underlying CNS barrier disintegration in the presence of oxidative stress, TNF-α release, and multiple sclerosis.Chimeric antigen receptor (CAR) T cell therapy has recently approved for CD-19-positive B-cell malignancies, such as acute lymphoblastic leukemia and diffuse large B-cell lymphoma in Japan. CAR-T therapy may develop cytokine release syndoromes as well as central nervous system complications (CRES/ICANS), including encephalopathy, consciousness distrubence, apahsia, seizure, motor weakness, and cerebral edema. Although the pathomechanism of CRES/ICANS remains unsolved, an appropriate intervention is important for patients. In addition, several chemotherapeutic agenets used before CAR-T cell therapy may also lead to the development of central nervous system disorders. Therefore, neurologists must be familiar with the complications of newly developed chemotherapies.Neurological immune-related adverse events (irAEs) associated with cancer treatment with immune checkpoint inhibitors (ICIs) are infrequent but are sometimes serious and require prompt diagnosis and management. Among diverse clinical subsets, meningoencephalitis, polyradiculoneuropathy, myasthenia gravis, and myositis are particularly important. The clinical presentation may be different from that of patients with those conditions unrelated to ICIs. A broad range of clinical symptoms complicates the diagnosis of autoimmune encephalitis. The clinical features of aseptic meningitis induced by classical drugs and ICIs are different. Polyradiculoneuropathy, usually diagnosed as Guillain-Barré syndrome or chronic inflammatory demyelinating polyneuropathy, requires prompt diagnosis. However, the clinical manifestations and laboratory findings of patients with polyradiculoneuropathy may be unique and differ from those in the preexisting disease subset. Although myasthenia gravis and myositis are usually independent diseases, it is often difficult to diagnose myasthenia gravis or myositis independently when the disease is associated with irAEs. We believe that inflammatory myopathy associated with ICIs is a novel disease entity accompanied by possible biomarkers of anti-striational antibodies. Discontinuation of immune checkpoint inhibitors and steroid treatment is recommended with a good response. A correct understanding of neurological adverse events is required for the best management of cancer patients.This article reviews the clinical features of toxicity in the peripheral and central nervous systems from anticancer drugs, including conventional cytotoxic chemotherapy, biologics, and targeted therapies, and excluding newer immunotherapies (immune checkpoint inhibitors and chimeric antigen receptor T cells). Neurologic complications from chemotherapy can be substantially disabling to patients and are being seen with increasing frequency because patients with cancer therapy are living longer and receiving multiple courses of anticancer regimens with combinations and longer duration. Clinicians, including neurologists, must know treatment-related neurotoxicity since discontinuation of the offending agent or dose adjustment may prevent further or permanent neurologic injury.Paraneoplastic neuropathy (PNS) is a neuromuscular disorder caused by the remote effects of tumors and is presumed to be primarily caused by an immune-mediated mechanism due to the appearance of anti-neuronal antibodies. In addition to the classical PNS syndromes already established as syndromes, there are an increasing number of reports of PNS that target membrane proteins on the cell surface such as channels. Diagnosing PNS, which often precedes associated tumors, is clinically important because it allows for early detection of tumors and early intervention.Metastatic brain tumors are malignant lesions that spread to the brain from a primary neoplasm such as cancer or sarcoma located in other body organs. Brain metastases tend to cause deterioration of neurological function and negatively affect patients quality of life. Control of brain metastases is important, following improved outcomes that are being observed in patients with cancer. PP242 mouse Recent advances in radiotherapy and drug therapy have led to a paradigm shift in the treatment of metastatic brain tumors. In this article, we review the clinical characterization of metastatic brain tumors that has reached a turning point in oncology.The ovarian follicle provides the oocyte with the ideal environment for growth and development in preparation for ovulation and fertilisation. The follicle undergoes many structural changes as it grows, including changes in vasculature, cell proliferation and differentiation and the formation of a fluid-filled antrum. These changes collectively create a low oxygen environment within the follicle. Thus, the oocyte itself develops in a potentially hypoxic environment. The survival of hypoxic tissues is controlled by hypoxia-inducible factors (HIFs) that are activated in a low oxygen state. The understanding of HIF pathways is growing across all fields of biology, and its role in ovarian development is steadily gaining clarity. One of the genes upregulated by HIF is a vascular endothelial growth factor, the main inducer of angiogenesis which is required for follicle development and corpus formation. Ovulation is also intrinsically linked to HIF activity through the ovulatory luteinising hormone surge increasing HIF expression.
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