The role of the choroid plexus in neutrophil invasion after traumatic brain injury.
Traumatic brain injury (TBI) frequently results in neuroinflammation, which includes the invasion of neutrophils. After TBI, neutrophils infiltrate the choroid plexus (CP), a site of the blood-cerebrospinal fluid (CSF) barrier (BCSFB), and accumulate in the CSF space near the injury, from where these inflammatory cells may migrate to brain parenchyma. We have hypothesized that the CP functions as an entry point for neutrophils to invade the injured brain. Using the controlled cortical impact model of TBI in rats and an in vitro model of the BCSFB, we show that the CP produces CXC chemokines, such as cytokine-induced neutrophil chemoattractant (CINC)-1 or CXCL1, CINC-2alpha or CXCL3, and CINC-3 or CXCL2. These chemokines are secreted both apically and basolaterally from the choroidal epithelium, a prerequisite for neutrophil migration across epithelial barriers. Consistent with these findings, we also provide electron microscopic evidence that neutrophils infiltrate the choroidal stroma and subsequently reach the intercellular space between choroidal epithelial cells. This is the first detailed analysis of the BCSFB function related to neutrophil trafficking. Our observations support the role of this barrier in posttraumatic neutrophil invasion.
Szmydynger-Chodobska
Joanna
J
Department of Emergency Medicine, The Warren Alpert Medical School of Brown University, Providence, Rhode Island 02903, USA. joanna_szmydynger-chodobska@brown.edu
Strazielle
Nathalie
N
Zink
Brian J
BJ
Ghersi-Egea
Jean-François
JF
Chodobski
Adam
A
D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology; D001930:Brain Injuries / Q000276:immunology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism; D054360:Chemokine CXCL1 / Q000378:metabolism; D019743:Chemokines, CXC / Q000235:genetics / Q000276:immunology; D002831:Choroid Plexus / Q000166:cytology / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology; D008297:Male; D009504:Neutrophils / Q000166:cytology / Q000276:immunology*; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
D054360:Chemokine CXCL1; D019743:Chemokines, CXC; C513297:Cxcl1 protein, rat; D016207:Cytokines; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha