In:
The Journal of Physiology, Wiley, Vol. 596, No. 3 ( 2018-02), p. 445-475
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0022-3751
,
1469-7793
DOI:
10.1113/tjp.2018.596.issue-3
Language:
English
Publisher:
Wiley
Publication Date:
2018
detail.hit.zdb_id:
1475290-6
SSG:
12