Roles of inflammation and the activated protein C pathway in the brain edema associated with cerebral venous sinus thrombosis.
OBJECTIVE
Increased blood-brain barrier (BBB) permeability, brain edema, and hemorrhage are important consequences of cerebral venous sinus thrombosis (CVST). The objective of this study was to define the role of the protein C pathway in the BBB permeability and edema elicited by experimental CVST. The role of neutrophil recruitment was also evaluated.


METHODS
Edema, BBB permeability, leukocyte-endothelial cell adhesion (LECA) and inflammatory cytokine levels were monitored in a murine model of CVST. The role of activated protein C (APC) was assessed in wild type mice (WT) receiving APC neutralizing antibody and in endothelial protein C receptor overexpressing mice (EPCR-tg). Neutrophil involvement was evaluated using an anti-CD18 antibody (Ab) and antineutrophil serum.


RESULTS
Brain edema and increases in BBB permeability and LECA were noted 48 hours after CVST. APC immunoblockade exacerbated these responses, while EPCR-tg exhibited blunted responses, as did WT treated with either antineutrophil serum or the CD18 Ab.


CONCLUSIONS
The protein C pathway protects the brain against the deleterious microvascular responses to CVST, a response that appears to be linked to the recruitment of inflammatory cells.
Nagai
Mutsumi
M
Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130, USA.
Terao
Satoshi
S
Yilmaz
Gokhan
G
Yilmaz
Cigdem E
CE
Esmon
Charles T
CT
Watanabe
Eiju
E
Granger
D Neil
DN
D000818:Animals; D001812:Blood-Brain Barrier / Q000201:enzymology / Q000473:pathology; D001929:Brain Edema / Q000201:enzymology* / Q000209:etiology / Q000503:physiopathology; D003392:Cranial Sinuses / Q000201:enzymology / Q000473:pathology; D004789:Enzyme Activation / Q000502:physiology; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020556:Neutrophil Infiltration / Q000502:physiology; D011486:Protein C / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D012851:Sinus Thrombosis, Intracranial / Q000150:complications / Q000201:enzymology* / Q000503:physiopathology
D018836:Inflammation Mediators; D011486:Protein C