Juxtavascular microglia migrate along brain microvessels following activation during early postnatal development.
Some parenchymal microglia in mammalian brain tissues, termed "juxtavascular microglia," directly contact the basal lamina of blood vessels; however, the functional consequences of this unique structural relationship are unknown. Here we used a rat brain slice model of traumatic brain injury to investigate the dynamic behavior of juxtavascular microglia following activation. Juxtavascular microglia were identified by confocal 3D reconstruction in tissue slices stained with a fluorescent lectin (FITC-IB4) that labels both microglia and blood vessel endothelial cells. Immunolabeling confirmed that juxtavascular cells were true parenchymal microglia (OX42+, ED2-) and not perivascular cells or pericytes. Time-lapse imaging in live tissue slices revealed that activating juxtavascular microglia withdraw most extant branches but often maintain contact with blood vessels, usually moving to the surface of a vessel within 1-4 h. Subsequently, some microglia migrate along the parenchymal surface of vessels, moving at rates up to 40 microm/h. Activated juxtavascular microglia sometimes repeatedly extend veil-like protrusions into the surrounding tissue, consistent with a role in tissue surveillance. Juxtavascular cells were twice as likely as nonjuxtavascular cells to be locomotory by 10 h in vitro, suggesting an enhanced activation response. Moreover, 38% of all juxtavascular cells migrated along a vessel, whereas this was never observed for a nonjuxtavascular cell. These observations identify a mobile subpopulation (10%-30%) of parenchymal microglia that activate rapidly and are preferentially recruited to the surfaces of blood vessels following brain tissue injury. The dynamic and sustained interaction of microglia with brain microvessels may facilitate signaling between injured brain parenchyma and components of the blood-brain barrier or circulating immune cells of the blood in vivo.
Grossmann
Ruth
R
Department of Biological Sciences, University of Iowa, Iowa City, Iowa 52242, USA.
Stence
Nick
N
Carr
Jenny
J
Fuller
Leah
L
Waite
Marc
M
Dailey
Michael E
ME
D000375:Aging / Q000276:immunology; D000818:Animals; D001808:Blood Vessels / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D001921:Brain / Q000098:blood supply* / Q000254:growth & development / Q000503:physiopathology; D001930:Brain Injuries / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D002465:Cell Movement / Q000276:immunology*; D005455:Fluorescent Antibody Technique; D005456:Fluorescent Dyes; D005911:Gliosis / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D006624:Hippocampus; D007157:Immunologic Surveillance / Q000502:physiology*; D017628:Microglia / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018613:Microscopy, Confocal; D018715:Microscopy, Video; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D005456:Fluorescent Dyes