Autoantibodies Biomarkers for Brain Injury Mohamed B Abou 自身抗体的生物标志物的脑损伤对穆罕默德B-精选文档-PPT文档.ppt
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1、Brain Injury,Little is known about the etiology of many brain diseases, such as Alzheimers Disease, Parkinsons Disease, Multiple Sclerosis, Amyotrophic Lateral Sclerosis (ALS), or Autism. Chemicals can cause brain injuries that resemble brain diseases, for example: a. Manganese causes brain injury s
2、imilar to that of Parkinson disease b. Organophosphate-Induced Delayed Neurotoxicity (OPIDN) has been misdiagnosed as Multiple Sclerosis.,The Brain,The brain contains approximately 200 billion cells (neurons) and a trillion supporting cells. Brain neurons are all formed before birth, and no new neur
3、onal cells are born after birth.,The Brain,The brain requires one fifth of the oxygen and energy (glucose) consumed by the body to maintain its function. The hourly flow of blood through the brain is approximately 13 gallons, which accounts for one fifth of the blood pumped by the heart.,Brain Regio
4、ns,The brain is divided into three sections: a. Forebrain: cerebrum, limbic system (amygdala,hippocampus, septum), thalamus, hypothalamus. b. Midbrain c.Hindbrain: Pons, medulla oblongata, cerebellum,Cerebral Cortex,Language Vision Higher-order processing Movement,Cerebral Cortex II,Corpus striatum
5、Degenerates in Parkinsons Paralysis Loss of sensory input Loss of reasoning, judgment, memory, etc,Limbic System,Emotion Memory Consolidation Storage Working memory Movement,Limbic System,Emotion Memory Consolidation Storage Working memory Movement,Cerebellum,Motor learning Posture Gait,Brain Suppor
6、ting Cells,Supporting cells continue to divide throughout life. A. Glial Cells: 1. Astocytes or astroglia: provide structural (Blood Brain Barrier) and nutritive support and form “glial” scar after injury. 2. Oligodendrocytes or oligodedroglia: form myelin sheath of axons in the CNS. 3. Microglia: A
7、ctivated after injury and act as scavengers taking up debris. B. Endothelial Cells: Form the walls of brain capillaries and the BBB.,Blood brain barrier,Blood Vessel,Blood brain barrier,The Blood Brain Barrier (BBB),Is formed by brain capillary walls endothelial cells: 1. Tight junctions 2. No fenes
8、tras 3. Few pinocytotic vesicles in the cytoplasm (BChE) 4. Increased mitochondria (active transport) 5. Basement membrane (AChE) 6. Astrocytic feet ensheathe 95% of endothelial cells 7.Pericytes with smooth muscle-like properties 8. P-glycoprotein (P-gp) to remove undesired substances.,Nerve Cell P
9、rocesses,Nervous System-Specific Proteins,1. Axons a. Neurofilament proteins (NFP) b. Tau proteins c. Tubulin 2. Dendrites Microtubule Associated Proteins-2 (MAP-2) 3. Myelin Myelin basic protein (MBP) 4. Astrocytes a. Glial Fibrillary Acidic Proteins (GFAP) b. S-100 protein,The Cytoskeleton,The cyt
10、oskeleton in the neuron consists of straight and parallel: a. 25-nm microtubules (- and -tublin) b. 10-nm neurofilaments c. Microtubule associated proteins (MAP-2 and Tau) that function as cross-bridges to link microtubules and neurofilaments. 2. The cytoskeleton gives the cell its shape and transpo
11、rt material within and outside the cell.,Neurofilament Proteins,Neurofilaments consist of 3 polypeptides: A 200-k Da, outer or high molecular weight protein (NFH), A 160-k Da, middle or medium molecular weight protein (NFM), and A 70-k Da, core and low-molecular weight protein (NFL). NFH is peripher
12、ally located, and especially vulnerable to injury and is an early marker to neuronal damage.,Tau Proteins,Tau Proteins are: Present almost exclusively in the axon. Involved in microtubule assembly and stabilization.,Tubulin,Tubulin is present in all cells 2. It is present at high level in the brain
13、where it comprise approximately 10% of brain protein. 3. Testes have high contents of tubulin,MAP-2,Microtubule Associated Proteins-2 (MAP-2): Are found exclusively in the somato-dendrites of the neurons They promote polymerization and stabilization of microtubules.,Myelin Basic Protein (MBP),MBP is
14、 a major constituent of the myelin that is formed by: 1.The supporting cells, oligodendrocytes in the central nervous system and 2. Schwann cells in the peripheral system.,Astrocytic Proteins,Astrocytes form the following proteins: 1. Glial Fibrillary Acidic Protein (GFAP) is secreted following axon
15、al injury to form gliotic scar. 2. S-100 is a calcium binding proteins that is formed in response to acute brain injury such as brain infarction and has been used to assess ischemic brain damage.,Autoantibodies against Brain Specific Proteins,Normally, small amounts of brain-specific proteins may le
16、ak into the circulation, where they react with B lymphocytes to form autoantibodies that are reactive against these proreins. Autoantibodies are increased with age. Damage to neuronal and glial cells in the brain or of the blood brain barrier (BBB), causes more leakage of these proteins into blood s
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