Pathology Of Multiple Sclerosis
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Pathology Of Multiple Sclerosis
Multiple sclerosis (MS) can be pathologically defined as the presence of distributed glial scars ( scleroses) in the central nervous system that must show dissemination in time (DIT) and in space (DIS) to be considered MS lesions. The scars that give the name to the condition are produced by the astrocyte cells attempting to heal old lesions. These glial scars are the remnants of previous demyelinating inflammatory lesions ( encephalomyelitis disseminata) which are produced by the one or more unknown underlying processes that are characteristic of MS. Apart of the disseminated lesions that define the condition, the CNS white matter normally shows other kinds of damage. At least five characteristics are present in CNS tissues of MS patients: Inflammation beyond classical white matter lesions (NAWM, NAGM), intrathecal Ig production with oligoclonal bands, an environment fostering immune cell persistence, Follicle-like aggregates in the meninges (B-cells mostly infected with EBV) ...
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Astrogliosis
Astrogliosis (also known as astrocytosis or referred to as reactive astrogliosis) is an abnormal increase in the number of astrocytes due to the destruction of nearby neurons from central nervous system (CNS) trauma, infection, ischemia, stroke, autoimmune responses or neurodegenerative disease. In healthy neural tissue, astrocytes play critical roles in energy provision, regulation of blood flow, homeostasis of extracellular fluid, homeostasis of ions and transmitters, regulation of synapse function and synaptic remodeling. Astrogliosis changes the molecular expression and morphology of astrocytes, in response to infection for example, in severe cases causing glial scar formation that may inhibit axon regeneration. Causes Reactive astrogliosis is a spectrum of changes in astrocytes that occur in response to all forms of CNS injury and disease. Changes due to reactive astrogliosis vary with the severity of the CNS insult along a graduated continuum of progressive alterations in ...
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Lymphocyte
A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic adaptive immunity), and B cells (for humoral, antibody-driven adaptive immunity). They are the main type of cell found in lymph, which prompted the name "lymphocyte". Lymphocytes make up between 18% and 42% of circulating white blood cells. Types The three major types of lymphocyte are T cells, B cells and natural killer (NK) cells. Lymphocytes can be identified by their large nucleus. T cells and B cells T cells (thymus cells) and B cells ( bone marrow- or bursa-derived cells) are the major cellular components of the adaptive immune response. T cells are involved in cell-mediated immunity, whereas B cells are primarily responsible for humoral immunity (relating to antibodies). The function of T cells and B cells is to recognize sp ...
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Glial Fibrillary Acidic Protein
Glial fibrillary acidic protein (GFAP) is a protein that is encoded by the ''GFAP'' gene in humans. It is a type III intermediate filament (IF) protein that is expressed by numerous cell types of the central nervous system (CNS), including astrocytes and ependymal cells during development. GFAP has also been found to be expressed in glomeruli and peritubular fibroblasts taken from rat kidneys, Leydig cells of the testis in both hamsters and humans, human keratinocytes, human osteocytes and chondrocytes and stellate cells of the pancreas and liver in rats. GFAP is closely related to the other three non-epithelial type III IF family members, vimentin, desmin and peripherin, which are all involved in the structure and function of the cell’s cytoskeleton. GFAP is thought to help to maintain astrocyte mechanical strength as well as the shape of cells, but its exact function remains poorly understood, despite the number of studies using it as a cell marker. The protein was named and ...
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Astrocyte
Astrocytes (from Ancient Greek , , "star" + , , "cavity", "cell"), also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord. They perform many functions, including biochemical control of endothelial cells that form the blood–brain barrier, provision of nutrients to the nervous tissue, maintenance of extracellular ion balance, regulation of cerebral blood flow, and a role in the repair and scarring process of the brain and spinal cord following infection and traumatic injuries. The proportion of astrocytes in the brain is not well defined; depending on the counting technique used, studies have found that the astrocyte proportion varies by region and ranges from 20% to 40% of all glia. Another study reports that astrocytes are the most numerous cell type in the brain. Astrocytes are the major source of cholesterol in the central nervous system. Apolipoprotein E transports cholesterol from astrocytes to neurons and other glial ...
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Neurofilament Protein
Neurofilaments (NF) are classed as type IV intermediate filaments found in the cytoplasm of neurons. They are protein polymers measuring 10 nm in diameter and many micrometers in length. Together with microtubules (~25 nm) and microfilaments (7 nm), they form the neuronal cytoskeleton. They are believed to function primarily to provide structural support for axons and to regulate axon diameter, which influences nerve conduction velocity. The proteins that form neurofilaments are members of the intermediate filament protein family, which is divided into six types based on their gene organization and protein structure. Types I and II are the keratins which are expressed in epithelia. Type III contains the proteins vimentin, desmin, peripherin and glial fibrillary acidic protein (GFAP). Type IV consists of the neurofilament proteins L, M, H and internexin. Type V consists of the nuclear lamins, and type VI consists of the protein nestin. The type IV intermedia ...
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Max Bielschowsky
Max Israel Bielschowsky (20 February 1869 – 15 August 1940) was a German neuropathologist born in Breslau. After receiving his medical doctorate from the University of Munich in 1893, he worked with Ludwig Edinger (1855–1918) at the Senckenberg Pathology Institute in Frankfurt-am-Main. At Senckenberg he learned histological staining techniques from Carl Weigert (1845–1904). From 1896 to 1904 he worked in Emanuel Mendel's (1839–1907) psychiatric laboratory in Berlin. In 1904 he joined Oskar Vogt (1870–1959) at the neurobiological laboratory at the University of Berlin, where he remained until 1933. Later in his career he worked at the psychiatric clinic at the University of Utrecht, and at the Cajal Institute in Madrid. He emigrated to the UK, where he died on 15 August 1940 in the Greater London area at 71 years of age. His oldest son, Franz David Bielschowsky, also emigrated to Sheffield, UK and subsequently to Dunedin, New Zealand where he pursued an eminent ...
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Axon
An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action potentials away from the nerve cell body. The function of the axon is to transmit information to different neurons, muscles, and glands. In certain sensory neurons (pseudounipolar neurons), such as those for touch and warmth, the axons are called afferent nerve fibers and the electrical impulse travels along these from the periphery to the cell body and from the cell body to the spinal cord along another branch of the same axon. Axon dysfunction can be the cause of many inherited and acquired neurological disorders that affect both the peripheral and central neurons. Nerve fibers are classed into three typesgroup A nerve fibers, group B nerve fibers, and group C nerve fibers. Groups A and B are myelinated, and group C are unmyelinated. ...
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CD68
CD68 ( Cluster of Differentiation 68) is a protein highly expressed by cells in the monocyte lineage (e.g., monocytic phagocytes, osteoclasts), by circulating macrophages, and by tissue macrophages (e.g., Kupffer cells, microglia). Structure and function Human CD68 is a Type I transmembrane glycoprotein, heavily glycosylated in its extracellular domain, with a molecular weight of 110 kD. Its primary sequence consists of 354 amino acids with predicted molecular weight of 37.4 kD if it were not glycosylated. The human CD68 protein is encoded by the "CD68" gene which maps to Chromosome 17. Other names or aliases for this gene in humans and other animals include: CD68 Molecule, CD68 Antigen, GP110, Macrosialin, Scavenger Receptor Class D, Member 1, SCARD1, and LAMP4. The mouse equivalent is known as "macrosialin". CD68 is functionally and evolutionarily related to other gene/protein family members, including: * the hematopoietic mucin-like family of molecules that includes leuko ...
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Luxol Fast Blue
Luxol fast blue stain, abbreviated LFB stain or simply LFB, is a commonly used stain to observe myelin under light microscopy, created by Heinrich Klüver and Elizabeth Barrera in 1953. LFB is commonly used to detect demyelination in the central nervous system (CNS), but cannot discern myelination in the peripheral nervous system. Procedure Luxol fast blue is a copper phthalocyanine dye that is soluble in alcohol and is attracted to bases found in the lipoproteins of the myelin sheath. Under the stain, myelin fibers appear blue, neuropil appears pink, and nerve cells appear purple. Tissues sections are treated over an extended period of time (usually overnight) and then differentiated with a lithium carbonate solution. Combination methods The combination of LFB with a variety of common staining methods provides the most useful and reliable method for the demonstration of pathological processes in the CNS. It is often combined with H&E stain (hematoxylin and eosin), which is abbrev ...
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Myelin
Myelin is a lipid-rich material that surrounds nerve cell axons (the nervous system's "wires") to insulate them and increase the rate at which electrical impulses (called action potentials) are passed along the axon. The myelinated axon can be likened to an electrical wire (the axon) with insulating material (myelin) around it. However, unlike the plastic covering on an electrical wire, myelin does not form a single long sheath over the entire length of the axon. Rather, myelin sheaths the nerve in segments: in general, each axon is encased with multiple long myelinated sections with short gaps in between called nodes of Ranvier. Myelin is formed in the central nervous system (CNS; brain, spinal cord and optic nerve) by glial cells called oligodendrocytes and in the peripheral nervous system (PNS) by glial cells called Schwann cells. In the CNS, axons carry electrical signals from one nerve cell body to another. In the PNS, axons carry signals to muscles and glands or from senso ...
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Eosin
Eosin is the name of several fluorescent acidic compounds which bind to and form salts with basic, or eosinophilic, compounds like proteins containing amino acid residues such as arginine and lysine, and stains them dark red or pink as a result of the actions of bromine on eosin. In addition to staining proteins in the cytoplasm, it can be used to stain collagen and muscle fibers for examination under the microscope. Structures, that stain readily with eosin, are termed eosinophilic. In the field of histology, Eosin Y is the form of eosin used most often as a histologic stain. Etymology Eosin was named by its inventor Heinrich Caro after the nickname (Eos) of a childhood friend, Anna Peters. Variants There are actually two very closely related compounds commonly referred to as eosin. Most often used is in histology is Eosin Y (also known as eosin Y ws, eosin yellowish, Acid Red 87, C.I. 45380, bromoeosine, bromofluoresceic acid, D&C Red No. 22); it has a very slightly yellowi ...
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