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Mostrando las entradas de junio, 2018

Herpes Virus Encephalitis in Adults: Current Knowledge and Old Myths

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Herpes simplex virus (HSV) encephalitis is uncommon in clinical practice, but is frequently suspected in patients with acute alterations of consciousness. Symptoms and physical signs are nonspecific, and diagnostic confirmation typically hinges on demonstration of viral DNA in cerebrospinal fluid.BrainMRI is helpful in diagnosis and provides prognostic information. Early initiation of intravenous acyclovir is essential to optimize the patient's chances of favorable recovery. HSV encephalitis can trigger an autoimmune reaction with the possible appearance of antibodies to neuronal surface antigens. Thus, recrudescence of neurologic impairment after a treated episode of HSV encephalitis warrants consideration of secondary autoimmune encephalitis. REFERENCE: Rabinstein AA. Herpes Virus Encephalitis in Adults: Current Knowledge and Old Myths. Neurol Clin. 2017 Nov;35(4):695-705. doi: 10.1016/j.ncl.2017.06.006. Epub 2017 Aug 10. Review. PubMed PMID: 28962808.

The dynamic blood–brain barrier

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With the endothelium as its central unit, theblood-brain barrier(BBB) is a complex multicellular structure separating the central nervous system (CNS) from the systemic circulation. Disruption of the BBB has now been implicated in a multitude of acute and chronic CNS disorders indicating the potentially devastating effects of BBB breakdown onbrainfunction. However, the healthy BBB is not an impermeable wall, but rather a communication 'centre', responding to and passing signals between the CNS andblood. New studies are identifying BBB-specific transport pathways that tightly regulate the entry and exit of molecules to and from thebrain. They are revealing a highly plasticbarrierin which dynamic changes in BBB components like paracellular tight junction complexes can contribute to BBB maintenance. Here, we provide a succinct overview of the current state-of-play in BBB research and summarize novel findings into BBB regulation in homeostatic regulation of thebrain. REFERENCE: Ke…

The blood-brain barrier

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Bloodvessels are critical to deliver oxygen and nutrients to all of the tissues and organs throughout the body. Thebloodvessels that vascularize the central nervous system (CNS) possess unique properties, termed theblood-brain barrier, which allow these vessels to tightly regulate the movement of ions, molecules, and cells between thebloodand thebrain. This precise control of CNS homeostasis allows for proper neuronal function and also protects the neural tissue from toxins and pathogens, and alterations of thesebarrierproperties are an important component of pathology and progression of different neurological diseases. The physiologicalbarrieris coordinated by a series of physical, transport, and metabolic properties possessed by the endothelial cells (ECs) that form the walls of thebloodvessels, and these properties are regulated by interactions with different vascular, immune, and neural cells. Understanding how these different cell populations interact to regulate thebarrierproper…

Microglia Development and function

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Proper development and function of the mammalian central nervous system (CNS) depend critically on the activity of parenchymal sentinels referred to as microglia. Although microglia were first described as ramified brain-resident phagocytes, research conducted over the past century has expanded considerably upon this narrow view and ascribed many functions to these dynamic CNS inhabitants. Microglia are now considered among the most versatile cells in the body, possessing the capacity to morphologically and functionally adapt to their ever-changing surroundings. Even in a resting state, the processes of microglia are highly dynamic and perpetually scan the CNS. Microglia are in fact vital participants in CNS homeostasis, and dysregulation of these sentinels can give rise to neurological disease. In this review, we discuss the exciting developments in our understanding of microglial biology, from their developmental origin to their participation in CNS homeostasis and pathophysiologic…

Coxsackievirus Adenovirus Receptor Loss Impairs Adult Neurogenesis, Synapse Content, and Hippocampus Plasticity

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Although we are beginning to understand the late stage of neurodegenerative diseases, the molecular defects associated with the initiation of impaired cognition are poorly characterized. Here, we demonstrate that in the adult brain, the coxsackievirus and adenovirus receptor (CAR) is located on neuron projections, at the presynapse in mature neurons, and on the soma of immature neurons in the hippocampus. In a proinflammatory or diseased environment, CAR is lost from immature neurons in the hippocampus. Strikingly, in hippocampi of patients at early stages of late-onset Alzheimer’s disease (AD), CAR levels are significantly reduced. Similarly, in triple-transgenic AD mice, CAR levels in hippocampi are low and further reduced after systemic inflammation. Genetic deletion of CAR from the mouse brain triggers deficits in adult neurogenesis and synapse homeostasis that lead to impaired hippocampal plasticity and cognitive deficits. We propose that post-translational CAR loss of function …