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Aquaporin-4
Aquaporin-4, also known as AQP-4, is a water channel protein encoded by the ''AQP4'' gene in humans. AQP-4 belongs to the aquaporin family of integral membrane proteins that conduct water through the cell membrane. A limited number of aquaporins are found within the central nervous system (CNS): AQP1, 3, 4, 5, 8, 9, and 11, but more exclusive representation of AQP1, 4, and 9 are found in the brain and spinal cord. AQP4 shows the largest presence in the cerebellum and spinal cord grey matter. In the CNS, AQP4 is the most prevalent aquaporin channel, specifically located at the perimicrovessel astrocyte foot processes, glia limitans, and ependyma. In addition, this channel is commonly found facilitating water movement near cerebrospinal fluid and vasculature. Aquaporin-4 was first identified in 1986. It was the first evidence of the existence of water transport channels. The method that was used to discover the existence of the transport channels was through knockout experiments. W ...
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Neuromyelitis Optica
Neuromyelitis optica spectrum disorders (NMOSD) are a spectrum of autoimmune diseases characterized by acute inflammation of the optic nerve (optic neuritis, ON) and the spinal cord ( myelitis).Banerjee S, Butcher R. Rituximab for the Treatment of Neuromyelitis Optica Spectrum Disorder nternet Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2021 Feb. Available from: https://www.ncbi.nlm.nih.gov/books/NBK571350/ Episodes of ON and myelitis can be simultaneous or successive. A relapsing disease course is common, especially in untreated patients. * Neuromyelitis optica (NMO) is a particular disease within the NMOSD spectrum. It is characterised by optic neuritis and longitudinally extensive myelitis. In more than 80% of NMO cases, the cause is immunoglobulin G autoantibodies to aquaporin 4 ( anti-AQP4), the most abundant water channel protein in the central nervous system. * Less common diseases with other manifestations are also part of the NMOSD spectrum. S ...
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Glymphatic System
The glymphatic system, glymphatic clearance pathway or paravascular system is an organ system for metabolic waste removal in the central nervous system (CNS) of vertebrates. According to this model, cerebrospinal fluid (CSF), an ultrafiltrated plasma fluid secreted by choroid plexuses in the cerebral ventricles, flows into the paravascular space around cerebral arteries, contacts and mixes with interstitial fluid (ISF) and solutes within the brain parenchyma, and exits via the cerebral venous paravascular spaces back into the subarachnoid space. The pathway consists of a para-arterial influx mechanism for CSF driven primarily by arterial pulsation, which "massages" the low-pressure CSF into the denser brain parenchyma, and the CSF flow is regulated during sleep by changes in parenchyma resistance due to expansion and contraction of the extracellular space. Clearance of soluble proteins, metabolites and excess extracellular fluid is accomplished through convective bulk f ...
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Cerebrospinal Fluid
Cerebrospinal fluid (CSF) is a clear, colorless Extracellular fluid#Transcellular fluid, transcellular body fluid found within the meninges, meningeal tissue that surrounds the vertebrate brain and spinal cord, and in the ventricular system, ventricles of the brain. CSF is mostly produced by specialized Ependyma, ependymal cells in the choroid plexuses of the ventricles of the brain, and absorbed in the arachnoid granulations. It is also produced by ependymal cells in the lining of the ventricles. In humans, there is about 125 mL of CSF at any one time, and about 500 mL is generated every day. CSF acts as a shock absorber, cushion or buffer, providing basic mechanical and immune system, immunological protection to the brain inside the Human skull, skull. CSF also serves a vital function in the cerebral autoregulation of cerebral blood flow. CSF occupies the subarachnoid space (between the arachnoid mater and the pia mater) and the ventricular system around and inside t ...
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Aquaporin
Aquaporins, also called water channels, are channel proteins from a larger family of major intrinsic proteins that form pores in the membrane of biological cells, mainly facilitating transport of water between cells. The cell membranes of a variety of different bacteria, fungi, animal and plant cells contain aquaporins through which water can flow more rapidly into and out of the cell than by diffusing through the phospholipid bilayer. Aquaporins have six membrane-spanning alpha helical domains with both carboxylic and amino terminals on the cytoplasmic side. Two hydrophobic loops contain conserved asparagine– proline– alanine ("NPA motif") which form a barrel surrounding a central pore-like region that contains additional protein density. Because aquaporins are usually always open and are prevalent in just about every cell type, this leads to a misconception that water readily passes through the cell membrane down its concentration gradient. Water can pass through th ...
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Blood–brain Barrier
The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that regulates the transfer of solutes and chemicals between the circulatory system and the central nervous system, thus protecting the brain from harmful or unwanted substances in the blood. The blood–brain barrier is formed by endothelial cells of the Capillary, capillary wall, astrocyte end-feet ensheathing the capillary, and pericytes embedded in the capillary basement membrane. This system allows the passage of some small molecules by passive transport, passive diffusion, as well as the selective and active transport of various nutrients, ions, organic anions, and macromolecules such as glucose and amino acids that are crucial to neural function. The blood–brain barrier restricts the passage of pathogens, the diffusion of solutes in the blood, and Molecular mass, large or Hydrophile, hydrophilic molecules into the cerebrospinal fluid, while a ...
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Amyotrophic Lateral Sclerosis
Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or—in the United States—Lou Gehrig's disease (LGD), is a rare, Terminal illness, terminal neurodegenerative disease, neurodegenerative disorder that results in the progressive loss of both upper and lower motor neurons that normally control Skeletal muscle, voluntary muscle contraction. ALS is the most common form of the motor neuron diseases. ALS often presents in its early stages with gradual muscle Spasticity, stiffness, Fasciculation, twitches, Muscle weakness, weakness, and Muscle atrophy, wasting. Motor neuron loss typically continues until the abilities to eat, speak, move, and, lastly, breathe are all lost. While only 15% of people with ALS also fully develop frontotemporal dementia, an estimated 50% face at least some minor difficulties with cognitive disorder, thinking and behavior. Depending on which of the aforementioned symptoms develops first, ALS is classified as ''limb-onset'' (b ...
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Alzheimer's Disease
Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems with language, disorientation (including easily getting lost), mood swings, loss of motivation, self-neglect, and behavioral issues. As a person's condition declines, they often withdraw from family and society. Gradually, bodily functions are lost, ultimately leading to death. Although the speed of progression can vary, the average life expectancy following diagnosis is three to twelve years. The causes of Alzheimer's disease remain poorly understood. There are many environmental and genetic risk factors associated with its development. The strongest genetic risk factor is from an allele of apolipoprotein E. Other risk factors include a history of head injury, clinical depression, and high blood pressure. The progression of the di ...
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Hydrocephalus
Hydrocephalus is a condition in which cerebrospinal fluid (CSF) builds up within the brain, which can cause pressure to increase in the skull. Symptoms may vary according to age. Headaches and double vision are common. Elderly adults with normal pressure hydrocephalus (NPH) may have poor balance, difficulty controlling urination, or mental impairment. In babies, there may be a rapid increase in head size. Other symptoms may include vomiting, sleepiness, seizures, and downward pointing of the eyes. Hydrocephalus can occur due to birth defects (primary) or can develop later in life (secondary). Hydrocephalus can be classified via mechanism into communicating, noncommunicating, ''ex vacuo'', and normal pressure hydrocephalus. Diagnosis is made by physical examination and medical imaging, such as a CT scan. Hydrocephalus is typically treated through surgery. One option is the placement of a shunt system. A procedure called an endoscopic third ventriculostomy has gained ...
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Ventricular System
In neuroanatomy, the ventricular system is a set of four interconnected cavities known as cerebral ventricles in the brain. Within each ventricle is a region of choroid plexus which produces the circulating cerebrospinal fluid (CSF). The ventricular system is continuous with the central canal of the spinal cord from the fourth ventricle, allowing for the flow of CSF to circulate. All of the ventricular system and the central canal of the spinal cord are lined with ependyma, a specialised form of epithelium connected by tight junctions that make up the blood–cerebrospinal fluid barrier. Structure The system comprises four ventricles: * lateral ventricles right and left (one for each hemisphere) * third ventricle * fourth ventricle There are several foramina, openings acting as channels, that connect the ventricles. The interventricular foramina (also called the foramina of Monro) connect the lateral ventricles to the third ventricle through which the cerebrospinal ...
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Azathioprine
Azathioprine, sold under the brand name Imuran, among others, is an immunosuppressive medication. It is used for the treatment of rheumatoid arthritis, granulomatosis with polyangiitis, Crohn's disease, ulcerative colitis, and systemic lupus erythematosus, and in kidney transplants to prevent transplant rejection, rejection. It is listed by the International Agency for Research on Cancer as a group 1 carcinogen, group 1 human carcinogen. It is taken by mouth or intravenous, injected into a vein. Common side effects include bone marrow suppression, bone-marrow suppression and vomiting. Bone-marrow suppression is especially common in people with a genetics, genetic deficiency of the enzyme thiopurine S-methyltransferase. Other serious risk factors include an increased risk of certain cancers. Use during pregnancy may result in harm to the baby. Azathioprine belongs to the purine analogues subclass of antimetabolites family of medications. It works via 6-thioguanine to disrupt the ...
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Immunosuppression
Immunosuppression is a reduction of the activation or efficacy of the immune system. Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reaction to treatment of other conditions. In general, deliberately induced immunosuppression is performed to prevent the body from rejecting an organ transplant. Additionally, it is used for treating graft-versus-host disease after a bone marrow transplant, or for the treatment of auto-immune diseases such as systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome, or Crohn's disease. This is typically done using medications, but may involve surgery (splenectomy), plasmapheresis, or radiation. A person who is undergoing immunosuppression, or whose immune system is weak for some other reasons (such as chemotherapy or HIV), is said to be ''immunocompromised''. Deliberately induced Administration of immunosuppressive medi ...
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