18 research outputs found

    Neuronal ICAM-5 Plays a Neuroprotective Role in Progressive Neurodegeneration

    Get PDF
    Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) leading to CNS inflammation and neurodegeneration. Current anti-inflammatory drugs have only limited efficacy on progressive neurodegenerative processes underlining the need to understand immune-mediated neuronal injury. Cell adhesion molecules play an important role for immune cell migration over the blood-brain barrier whereas their role in mediating potentially harmful contacts between invading immune cells and neurons is incompletely understood. Here, we assess the role of the CNS-specific neuronal adhesion molecule ICAM-5 using experimental autoimmune encephalomyelitis (EAE), an animal model of MS. ICAM-5 knockout mice show a more severe EAE disease course in the chronic phase indicating a neuroprotective function of ICAM-5 in progressive neurodegeneration. In agreement with the predominant CNS-specific function of ICAM-5, lymphocyte function-associated antigen 1 (LFA-1)/ICAM-1 contact between antigen-presenting cells and T helper (Th)17 cells in EAE is not affected by ICAM-5. Strikingly, intrathecal application of the shed soluble form, sICAM-5, ameliorates EAE disease symptoms and thus might serve locally as an endogenous neuronal defense mechanism which is activated upon neuroinflammation in the CNS. In humans, cerebrospinal fluid from patients suffering from progressive forms of MS shows decreased sICAM-5 levels, suggesting a lack of this endogenous protective pathway in these patient groups. Overall, our study points toward a novel role of ICAM-5 in CNS autoinflammation in progressive EAE/MS

    Intensive heart rhythm monitoring to decrease ischemic stroke and systemic embolism - the Find-AF 2 study - rationale and design

    Get PDF
    Background Atrial fibrillation (AF) is one of the most frequent causes of stroke. Several randomized trials have shown that prolonged monitoring increases the detection of AF, but the effect on reducing recurrent cardioembolism, i.e. ischemic stroke and systemic embolism, remains unknown. We aim to evaluate whether a risk-adapted, intensified heart rhythm monitoring with consequent guideline conform treatment, which implies initiation of oral anticoagulation (OAC), leads to a reduction of recurrent cardioembolism. Methods Find-AF 2 is a randomized, controlled, open-label parallel multicenter trial with blinded endpoint assessment. 5,200 patients ≥ 60 years of age with symptomatic ischemic stroke within the last 30 days and without known AF will be included at 52 study centers with a specialized stroke unit in Germany. Patients without AF in an additional 24-hour Holter ECG after the qualifying event will be randomized in a 1:1 fashion to either enhanced, prolonged and intensified ECG-monitoring (intervention arm) or standard of care monitoring (control arm). In the intervention arm, patients with a high risk of underlying AF will receive continuous rhythm monitoring using an implantable cardiac monitor (ICM) whereas those without high risk of underlying AF will receive repeated 7-day Holter ECGs. The duration of rhythm monitoring within the control arm is up to the discretion of the participating centers and is allowed for up to 7 days. Patients will be followed for at least 24 months. The primary efficacy endpoint is the time until recurrent ischemic stroke or systemic embolism occur. Conclusions The Find-AF 2 trial aims to demonstrate that enhanced, prolonged and intensified rhythm monitoring results in a more effective prevention of recurrent ischemic stroke and systemic embolism compared to usual care

    There is inadequate evidence to support the division of the genus Borrelia

    Get PDF
    There are surely scientific, genetic or ecological 60 arguments which show that differences exist between the relapsing fever (RF) spirochaetes and the Lyme borreliosis (LB) group of spirochaetes, both of which belong to the genus Borrelia. In a recent publication, Adeolu and Gupta (Adeolu & 63 Gupta, 2014) proposed dividing the genus Borrelia into two genera on the basis of genetic differences revealed by comparative genomics. The new genus name for the LB group of spirochaetes, Borreliella, has subsequently been entered in GenBank for some species of the group and in a validation list (List of new names and new combinations previously effectively, but not validly, published) (Oren & Garrity, 2015). However, rapidly expanding scientific knowledge and considerable conflicting evidence combined with the adverse consequences of splitting the genus Borrelia make such a drastic step somewhat premature. In our opinion, the basis of this division rests on preliminary evidence and should be rescinded

    MR imaging of therapy-induced changes of bone marrow

    Get PDF
    MR imaging of bone marrow infiltration by hematologic malignancies provides non-invasive assays of bone marrow cellularity and vascularity to supplement the information provided by bone marrow biopsies. This article will review the MR imaging findings of bone marrow infiltration by hematologic malignancies with special focus on treatment effects. MR imaging findings of the bone marrow after radiation therapy and chemotherapy will be described. In addition, changes in bone marrow microcirculation and metabolism after anti-angiogenesis treatment will be reviewed. Finally, new specific imaging techniques for the depiction of regulatory events that control blood vessel growth and cell proliferation will be discussed. Future developments are directed to yield comprehensive information about bone marrow structure, function and microenvironment

    Neuronal ICAM-5 plays a neuroprotective role in progressive neurodegeneration

    No full text
    Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) leading leading to CNS inflammation and neurodegeneration. Current anti-inflammatory drugs have only limited efficacy on progressive neurodegenerative processes underlining the need to understand immune-mediated neuronal injury. Cell adhesion molecules play an important role for immune cell migration migration over the blood-brain barrier whereas their role in mediating potentially harmful contacts between between invading immune cells and neurons is incompletely understood. Here, we assess the role of the the CNS-specific neuronal adhesion molecule ICAM-5 using experimental autoimmune encephalomyelitis (EAE), an animal model of MS. ICAM-5 knockout mice show a more severe EAE disease course in the chronic chronic phase indicating a neuroprotective function of ICAM-5 in progressive neurodegeneration. In agreement agreement with the predominant CNS-specific function of ICAM-5, lymphocyte function-associated antigen antigen 1 (LFA-1)/ICAM-1 contact between antigen-presenting cells and T helper (Th)17 cells in EAE is is not affected by ICAM-5. Strikingly, intrathecal application of the shed soluble form, sICAM-5, ameliorates ameliorates EAE disease symptoms and thus might serve locally as an endogenous neuronal defense mechanism mechanism which is activated upon neuroinflammation in the CNS. In humans, cerebrospinal fluid from patients patients suffering from progressive forms of MS shows decreased sICAM-5 levels, suggesting a lack of of this endogenous protective pathway in these patient groups. Overall, our study points toward a novel novel role of ICAM-5 in CNS autoinflammation in progressive EAE/MS
    corecore