FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2760852110> ?p ?o ?g. }

• W2760852110 endingPage "475" @default.
• W2760852110 startingPage "445" @default.
• W2760852110 abstract "Key points It is unclear precisely how macromolecules (e.g. endogenous proteins and exogenous immunotherapeutics) access brain tissue from the cerebrospinal fluid (CSF). We show that transport at the brain–CSF interface involves a balance between Fickian diffusion in the extracellular spaces at the brain surface and convective transport in perivascular spaces of cerebral blood vessels. Intrathecally-infused antibodies exhibited size-dependent access to the perivascular spaces and tunica media basement membranes of leptomeningeal arteries. Perivascular access and distribution of full-length IgG could be enhanced by intrathecal co-infusion of hyperosmolar mannitol. Pores or stomata present on CSF-facing leptomeningeal cells ensheathing blood vessels in the subarachnoid space may provide unique entry sites into the perivascular spaces from the CSF. These results illuminate new mechanisms likely to govern antibody trafficking at the brain–CSF interface with relevance for immune surveillance in the healthy brain and insights into the distribution of therapeutic antibodies. Abstract The precise mechanisms governing the central distribution of macromolecules from the cerebrospinal fluid (CSF) to the brain and spinal cord remain poorly understood, despite their importance for physiological processes such as antibody trafficking for central immune surveillance, as well as several ongoing intrathecal clinical trials. In the present study, we clarify how IgG and smaller single-domain antibodies (sdAb) distribute throughout the whole brain in a size-dependent manner after intrathecal infusion in rats using ex vivo fluorescence and in vivo three-dimensional magnetic resonance imaging. Antibody distribution was characterized by diffusion at the brain surface and widespread distribution to deep brain regions along the perivascular spaces of all vessel types, with sdAb accessing a four- to seven-fold greater brain area than IgG. Perivascular transport involved blood vessels of all caliber and putative smooth muscle and astroglial basement membrane compartments. Perivascular access to smooth muscle basement membrane compartments also exhibited size-dependence. Electron microscopy was used to show stomata on leptomeningeal coverings of blood vessels in the subarachnoid space as potential access points allowing substances in the CSF to enter the perivascular space. Osmolyte co-infusion significantly enhanced perivascular access of the larger antibody from the CSF, with intrathecal 0.75 m mannitol increasing the number of perivascular profiles per slice area accessed by IgG by ∼50%. The results of the present study reveal potential distribution mechanisms for endogenous IgG, which is one of the most abundant proteins in the CSF, as well as provide new insights with respect to understanding and improving the drug delivery of macromolecules to the central nervous system via the intrathecal route." @default.
• W2760852110 created "2017-10-20" @default.
• W2760852110 creator A5002549369 @default.
• W2760852110 creator A5004323167 @default.
• W2760852110 creator A5015184178 @default.
• W2760852110 creator A5021443355 @default.
• W2760852110 creator A5023811528 @default.
• W2760852110 creator A5031719922 @default.
• W2760852110 creator A5043006925 @default.
• W2760852110 creator A5049529673 @default.
• W2760852110 creator A5050129474 @default.
• W2760852110 creator A5071217862 @default.
• W2760852110 creator A5090108909 @default.
• W2760852110 date "2017-12-18" @default.
• W2760852110 modified "2023-10-16" @default.
• W2760852110 title "Intrathecal antibody distribution in the rat brain: surface diffusion, perivascular transport and osmotic enhancement of delivery" @default.
• W2760852110 cites W116391231 @default.
• W2760852110 cites W1265793160 @default.
• W2760852110 cites W1479991645 @default.
• W2760852110 cites W1511552436 @default.
• W2760852110 cites W1544776535 @default.
• W2760852110 cites W1588685142 @default.
• W2760852110 cites W1788181016 @default.
• W2760852110 cites W1852301381 @default.
• W2760852110 cites W1932367580 @default.
• W2760852110 cites W1969375579 @default.
• W2760852110 cites W1969584460 @default.
• W2760852110 cites W1972606676 @default.
• W2760852110 cites W1973627211 @default.
• W2760852110 cites W1974078894 @default.
• W2760852110 cites W1975635783 @default.
• W2760852110 cites W1978506065 @default.
• W2760852110 cites W1985530741 @default.
• W2760852110 cites W1990192115 @default.
• W2760852110 cites W1992014046 @default.
• W2760852110 cites W1992375147 @default.
• W2760852110 cites W1999116330 @default.
• W2760852110 cites W2002065049 @default.
• W2760852110 cites W2003200494 @default.
• W2760852110 cites W2004683657 @default.
• W2760852110 cites W2006219651 @default.
• W2760852110 cites W2009194888 @default.
• W2760852110 cites W2009902832 @default.
• W2760852110 cites W2011139878 @default.
• W2760852110 cites W2015352052 @default.
• W2760852110 cites W2015541518 @default.
• W2760852110 cites W2018963238 @default.
• W2760852110 cites W2018971279 @default.
• W2760852110 cites W2021493191 @default.
• W2760852110 cites W2022906574 @default.
• W2760852110 cites W2022908099 @default.
• W2760852110 cites W2024955728 @default.
• W2760852110 cites W2026275665 @default.
• W2760852110 cites W2026364951 @default.
• W2760852110 cites W2028486216 @default.
• W2760852110 cites W2028596291 @default.
• W2760852110 cites W2028623620 @default.
• W2760852110 cites W2034781062 @default.
• W2760852110 cites W2040880670 @default.
• W2760852110 cites W2042683896 @default.
• W2760852110 cites W2046026976 @default.
• W2760852110 cites W2050997734 @default.
• W2760852110 cites W2052283106 @default.
• W2760852110 cites W2052688891 @default.
• W2760852110 cites W2056201078 @default.
• W2760852110 cites W2059860021 @default.
• W2760852110 cites W2060279158 @default.
• W2760852110 cites W2060906896 @default.
• W2760852110 cites W2061514369 @default.
• W2760852110 cites W2065410730 @default.
• W2760852110 cites W2069465707 @default.
• W2760852110 cites W2073209227 @default.
• W2760852110 cites W2079390303 @default.
• W2760852110 cites W2080824691 @default.
• W2760852110 cites W2084861350 @default.
• W2760852110 cites W2087434342 @default.
• W2760852110 cites W2089331105 @default.
• W2760852110 cites W2090548458 @default.
• W2760852110 cites W2091659898 @default.
• W2760852110 cites W2091833224 @default.
• W2760852110 cites W2096525076 @default.
• W2760852110 cites W2105197440 @default.
• W2760852110 cites W2106495485 @default.
• W2760852110 cites W2112026930 @default.
• W2760852110 cites W2115687133 @default.
• W2760852110 cites W2125136428 @default.
• W2760852110 cites W2127716652 @default.
• W2760852110 cites W2139748189 @default.
• W2760852110 cites W2143238511 @default.
• W2760852110 cites W2147493255 @default.
• W2760852110 cites W2152719134 @default.
• W2760852110 cites W2152765608 @default.
• W2760852110 cites W2156755609 @default.
• W2760852110 cites W2161745933 @default.
• W2760852110 cites W2163225965 @default.
• W2760852110 cites W2166233935 @default.
• W2760852110 cites W2167127477 @default.
• W2760852110 cites W2167183660 @default.

• next