Synaptotagmin 4 Supports Spontaneous Axon Sprouting after Spinal Cord Injury.

Injuries to the central nervous system (CNS) can cause severe neurological deficits. Axonal regrowth is a fundamental process for the reconstruction of compensatory neuronal networks after injury; however, it is extremely limited in the adult mammalian CNS. In this study, we conducted a loss-of-function genetic screen in cortical neurons, combined with a Web resource-based phenotypic screen, and identified synaptotagmin 4 (Syt4) as a novel regulator of axon elongation.

Expression and distribution of hypoxia-inducible factor-1α and vascular endothelial growth factor in comparison between radiation necrosis and tumor tissue in metastatic brain tumor: A case report.

We report the case of a 70-year-old woman with metastatic brain tumors who underwent surgical removal of the tumor and radiation necrosis. The patient had a history of colon cancer and had undergone surgical removal of a left occipital tumor. Histopathological evaluation revealed a metastatic brain tumor.

Lysophosphatidic acid stimulates pericyte migration via LPA receptor 1.

Lysophosphatidic acid (LPA) is a bioactive compound known to regulate various vascular functions. However, despite the fact that many vascular functions are regulated by peri-vascular cells such as pericytes, the effect of LPA on brain pericytes has not been fully evaluated. Thus, we designed this study to evaluate the effects of LPA on brain pericytes.

Circulating factors that influence the central nervous system remyelination.

Injury in the central nervous system leads to neurological deficits, depending on the disruption of neural networks. Remyelination, which occurs partially and spontaneously, is a critical process in the regeneration of neural networks to recover from neurological deficits. Remyelination depends on the development of oligodendrocytes, including the proliferation of oligodendrocyte precursor cells (OPCs) and the differentiation of OPCs into mature oligodendrocytes to form myelin.

Microglial ASD-related genes are involved in oligodendrocyte differentiation.

Autism spectrum disorders (ASD) are associated with mutations of chromodomain-helicase DNA-binding protein 8 (Chd8) and tuberous sclerosis complex 2 (Tsc2). Although these ASD-related genes are detected in glial cells such as microglia, the effect of Chd8 or Tsc2 deficiency on microglial functions and microglia-mediated brain development remains unclear. In this study, we investigated the role of microglial Chd8 and Tsc2 in cytokine expression, phagocytosis activity, and neuro/gliogenesis from neural stem cells (NSCs) in vitro.

Interleukin-17A regulates ependymal cell proliferation and functional recovery after spinal cord injury in mice.

Ependymal cells have been suggested to act as neural stem cells and exert beneficial effects after spinal cord injury (SCI). However, the molecular mechanism underlying ependymal cell regulation after SCI remains unknown. To examine the possible effect of IL-17A on ependymal cell proliferation after SCI, we locally administrated IL-17A neutralizing antibody to the injured spinal cord of a contusion SCI mouse model, and revealed that IL-17A neutralization promoted ependymal cell proliferation, which was paralleled by functional recovery and axonal reorganization of both the corticospinal tract and the raphespinal tract.

Dimethylarginine dimethylaminohydrolase 1 as a novel regulator of oligodendrocyte differentiation in the central nervous system remyelination.

Remyelination is a regenerative process that restores the lost neurological function and partially depends on oligodendrocyte differentiation. Differentiation of oligodendrocytes spontaneously occurs after demyelination, depending on the cell intrinsic mechanisms. By combining a loss-of-function genomic screen with a web-resource-based candidate gene identification approach, we identified that dimethylarginine dimethylaminohydrolase 1 (DDAH1) is a novel regulator of oligodendrocyte differentiation.

[Molecular mechanism of brain development and neurodevelopmental disorders regulated be neuroimmune system].

Recent studies have revealed that neuroimmune system is involved in the brain development and the pathogenesis of neurological diseases. However, it remains unclear how neuroimmune system modulates brain functions at a molecular level. We identified the role of immune cells in brain development and inflammatory neurological diseases.

Age-dependent decline in remyelination capacity is mediated by apelin-APJ signaling.

Age-related regeneration failure in the central nervous system can occur as a result of a decline in remyelination efficacy. The responsiveness of myelin-forming cells to signals for remyelination is affected by aging-related epigenetic modification; however, the molecular mechanism is not fully clarified. In the present study, we report that the apelin receptor (APJ) mediates remyelination efficiency with age.

A novel protocol for three-dimensional rotational venography with low-dose contrast media in preoperative angiography of brain tumours.

Aim: The most appropriate imaging protocol for three-dimensional rotational venography (3D RV) has not been established. The aim of this study was to optimise the protocol for 3D RV with low-dose contrast media using time-density curve analysis.

Methods: Twenty-five consecutive patients with brain tumours who received preoperative assessment with 3D RV were retrospectively collected and included in this study.

Microglia suppress the secondary progression of autoimmune encephalomyelitis.

Secondary progressive multiple sclerosis (SPMS) is an autoimmune disease of the central nervous system (CNS) characterized by progressive motor dysfunction, sensory deficits, and visual problems. The pathological mechanism of SPMS remains poorly understood. In this study, we investigated the role of microglia, immune cells in the CNS, in a secondary progressive form of experimental autoimmune encephalomyelitis (EAE), the mouse model of SPMS.

Microglia promote the proliferation of neural precursor cells by secreting osteopontin.

Microglia are central nervous system-resident immune cells that play a crucial role in brain development by interacting with neural precursor cells (NPCs). It has been reported that microglia regulate the number of NPC by phagocytosis, inducing apoptosis, and promoting proliferation. Microglia surrounding the subventricular zone express osteopontin (OPN) during brain development.

Function of Lymphocytes in Oligodendrocyte Development.

Oligodendrocytes generate myelin sheaths to promote rapid neurotransmission in the central nervous system (CNS). During brain development, oligodendrocyte precursor cells (OPCs) are generated in the medial ganglionic eminence, lateral ganglionic eminence, and dorsal pallium. OPCs proliferate and migrate throughout the CNS at the embryonic stage.

Inhibiting repulsive guidance molecule-a suppresses secondary progression in mouse models of multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system that is characterized by motor deficits, fatigue, pain, cognitive impairment, and sensory and visual dysfunction. Secondary progressive multiple sclerosis (SPMS) is a progressive form of MS that develops from relapsing-remitting MS. Repulsive guidance molecule-a (RGMa) has diverse functions, including axon growth inhibition and immune regulation.

B lymphocytes: Crucial contributors to brain development and neurological diseases.

The immune system is a major contributor to brain homeostasis and pathogenesis of neurological diseases. However, the role of B lymphocytes (cells) in the brain is poorly understood. In this review, we describe the functions of the different subtypes of B cells in brain development and neurological diseases.

The role of immune cells in brain development and neurodevelopmental diseases.

During brain development, the generation of neurons and glial cells is rigorously regulated by diverse mechanisms including the immune system. Dysfunction of the developing system results in the onset of neurodevelopmental disorders and psychological disorders. Recent studies have demonstrated that the immune system is implicated in brain development.

B-1a lymphocytes promote oligodendrogenesis during brain development.

During brain development, the immune system mediates neurogenesis, gliogenesis and synapse formation. However, it remains unclear whether peripheral lymphocytes contribute to brain development. Here we identified the subtypes of lymphocytes that are present in neonatal mouse brains and investigated their functions.

Inhibition of RGMa alleviates symptoms in a rat model of neuromyelitis optica.

Neuromyelitis optica (NMO) is an autoimmune disease associated with NMO immunoglobulin G (NMO-IgG), an antibody that selectively binds to the aquaporin-4. Here, we established a localized NMO model by injecting NMO-IgG into the spinal cord, and assessed the efficacy of treating its NMO-like symptoms by blocking repulsive guidance molecule-a (RGMa), an axon growth inhibitor. The model showed pathological features consistent with NMO.

Selective Expression of Osteopontin in ALS-resistant Motor Neurons is a Critical Determinant of Late Phase Neurodegeneration Mediated by Matrix Metalloproteinase-9.

Differential vulnerability among motor neuron (MN) subtypes is a fundamental feature of amyotrophic lateral sclerosis (ALS): fast-fatigable (FF) MNs are more vulnerable than fast fatigue-resistant (FR) or slow (S) MNs. The reason for this selective vulnerability remains enigmatic. We report here that the extracellular matrix (ECM) protein osteopontin (OPN) is selectively expressed by FR and S MNs and ALS-resistant motor pools, whereas matrix metalloproteinase-9 (MMP-9) is selectively expressed by FF MNs.

Repulsive guidance molecule-a is involved in Th17-cell-induced neurodegeneration in autoimmune encephalomyelitis.

Multiple sclerosis (MS) is a chronic autoimmune disease characterized by inflammation, demyelination, and neurodegeneration in the CNS. Although it is important to prevent neurodegeneration for alleviating neurological disability, the molecular mechanism of neurodegeneration remains largely unknown. Here, we report that repulsive guidance molecule-a (RGMa), known to regulate axonal growth, is associated with neurodegeneration in experimental autoimmune encephalomyelitis (EAE), a mouse model of MS.

Osteopontin is an alpha motor neuron marker in the mouse spinal cord.

Motor neurons (MNs) are designated as alpha/gamma and fast/slow based on their target sites and the types of muscle fibers innervated; however, few molecular markers that distinguish between these subtypes are available. Here we report that osteopontin (OPN) is a selective marker of alpha MNs in the mouse spinal cord. OPN was detected in approximately 70% of postnatal choline acetyltransferase (ChAT)-positive MNs with relatively large somas, but not in those with smaller somas.