User talk:TPCriswell

Intramural periarterial drainage (IPAD)
There are two major extracellular, extravascular fluids associated with the brain; cerebrospinal fluid (CSF) in the ventricles and subarachnoid spaces and interstitial fluid (ISF) between cells within the CNS parenchyma. In most organs of the body, interstitial fluid, metabolites and antigen presenting cells drain to regional lymph nodes along well-defined lymphatic vessels. However, there are no conventional lymphatic vessels in the CNS, but there are lymphatic drainage pathways by which CSF and ISF drain to regional lymph nodes. These pathways are located in the walls of cerebral arterioles, and are referred to as 'intramural periarterial drainage (IPAD)' pathways.

ISF drainage from the brain
Lymphatic drainage of ISF and solutes occurs along basement membranes in the walls of cerebral capillaries and arteries in an opposite direction to blood flow at an estimated rate of 0.11–0.29 µl/min/g of brain. ISF and solutes enter the basement membranes of the capillaries between astrocyte end-feet which surround the vessel. These solutes travel in the opposite direction to blood flow to reach arterioles. Once the ISF reaches arterioles, it drains within the basement membranes surrounding spiral smooth muscle cells in the artery wall. These solutes follow this spiralling trajectory towards cortical and leptomeningeal arteries at the brain’s surface, and ultimately to cervical lymph nodes.

Evidence for IPAD pathways
Evidence for lymphatic drainage along walls of cerebral blood vessels is derived from experimental studies and from observations in human cerebral amyloid angiopathy (CAA). When small volumes of soluble tracer are injected (0.5 µl injected over a period of 2 min) into the ISF of grey matter of the mouse striatum or hippocampus, tracer initially diffuses through the extracellular spaces of the brain but within 5 min has entered basement membranes in the walls of capillaries and cerebral arteries to drain out of the brain. If larger volumes are injected, tracer is not retained within the brain parenchyma and may pass into CSF in the ventricles. Flow of ISF and tracers out of the brain along blood vessel walls is specifically along basement membranes between capillary endothelium and glia limitans and along basement membranes that surround smooth muscle cells in the tunica media of cerebral arteries in a three-dimensional network. Studies using radioactive human serum albumin have shown that tracers drain from the brain to cervical lymph nodes along the walls of leptomeningeal arteries and the internal carotid artery in the neck. These experiments have also shown that only 5–10 % of tracer injected into the striatum leaks into the CSF, suggesting that the lymphatic drainage of ISF by the pericapillary and periarterial route is largely separate from the CSF. One important role of IPAD along basement membranes lies in the transfer of soluble antigens from the CNS parenchyma to regional lymph nodes. The basement membrane pathways are too narrow to allow passage of antigen presenting cells and lymphocytes from the brain to regional lymph nodes and this may be a major factor for the immunological privilege of the brain.

Significance of IPAD for neurodegenerative disease
Another key role for intramural perivascular drainage along basement membranes is the elimination of solutes, such as soluble amyloid β (Aβ) from the brain. As arteries age, perivascular lymphatic drainage becomes less efficient and insoluble, fibrillary Aβ among other amyloids is deposited in the walls of cerebral capillaries and arteries as cerebral amyloid angiopathy (CAA). The distribution of Aβ in vascular basement membranes in the early stages of CAA in the human brain is exactly the same as the distribution of soluble tracers injected into the mouse brain, i.e. in capillary basement membranes and in basement membranes in the tunica media of arteries. In effect, Aβ produced by the brain acts as a natural tracer for lymphatic drainage in the human and mouse brain. Basement membranes of arterial endothelium and basement membranes on the outer aspects of arteries are devoid of soluble tracer in the experimental animals and of Aβ in the early stages of human CAA. Thus, experimental data derived from mouse studies on lymphatic drainage of the brain are highly relevant for the human brain, CAA and Alzheimer’s disease.

Other pathways of extracellular fluid movements
The walls of cerebral arteries and capillaries are not only routes for the lymphatic drainage of ISF and solutes out of the brain, they are also routes by which CSF and tracers enter the brain from the subarachnoid space and mix with ISF. Injection of horseradish peroxidase and a variety of fluorescent tracers into the CSF results in their entry into the brain alongside cortical arteries and penetration of tracers into basement membranes surrounding capillaries. This system has been termed convective influx or the glymphatic system as entry of tracers from the CSF into the ISF of the brain parenchyma involves aquaporin 4 in perivascular astrocytes.

Your submission at Articles for creation: Intramural periarterial drainage (IPAD) (May 16)
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Primefac (talk) 16:47, 16 May 2017 (UTC)

Draft:Intramural periarterial drainage (IPAD) concern
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Thank you for your attention. HasteurBot (talk) 01:34, 17 October 2017 (UTC)

Draft:Intramural periarterial drainage (IPAD) concern
Hi there, I'm HasteurBot. I just wanted to let you know that Draft:Intramural periarterial drainage (IPAD), a page you created, has not been edited in 5 months. The Articles for Creation space is not an indefinite storage location for content that is not appropriate for articlespace.

If your submission is not edited soon, it could be nominated for deletion. If you would like to attempt to save it, you will need to improve it.

You may request Userfication of the content if it meets requirements.

If the deletion has already occured, instructions on how you may be able to retrieve it are available at WP:REFUND/G13.

Thank you for your attention. HasteurBot (talk) 01:32, 15 May 2018 (UTC)