Activation of vascular endothelial cells and perivascular cells by systemic inflammation-an immunohistochemical study of postmortem human brain tissues.
We investigated postmortem human brain tissues to determine whether systemic inflammation causes activation of vascular endothelial cells and perivascular cells. In some cases, we used serum concentrations of an acute-phase reactant, C-reactive protein (CRP), as an index of systemic inflammation. Since the serum concentration of CRP at the agonal stage was available only in a limited number of patients, we estimated the degree of systemic inflammation by the intensity of immunohistochemical staining of the residual blood in brain tissue for CRP. Expressions of intercellular adhesion molecule (ICAM)-1, CD40 and cyclooxygenase (COX)-2 were used as markers for activation of vascular endothelial cells. Activation of perivascular cells was estimated by the occurrence of HLA-DR- and CD68-positive perivascular cells. In cases without brain lesions, activation of vascular endothelial cells and perivascular cells was related to the degree of systemic inflammation. In cases with brain lesions, these cells are often activated even in the absence of systemic inflammation. We suggest that inflammatory stimuli derived from the peripheral blood and the brain parenchyma adjunctly activate vascular cells. Under such circumstances, low-grade inflammation in the pre-existing brain lesions might enhance inflammatory signaling to the brain parenchyma from the periphery. The results of this study could explain the vulnerability of neurological patients to delirium caused by systemic inflammatory conditions.
Uchikado
Hirotake
H
Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, 156-8585, Tokyo, Japan.
Akiyama
Haruhiko
H
Kondo
Hiromi
H
Ikeda
Kenji
K
Tsuchiya
Kuniaki
K
Kato
Masanori
M
Oda
Tatsuro
T
Togo
Takashi
T
Iseki
Eizo
E
Kosaka
Kenji
K
D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001927:Brain Diseases / Q000378:metabolism / Q000473:pathology*; D002097:C-Reactive Protein / Q000378:metabolism*; D019013:CD40 Antigens / Q000378:metabolism; D024141:Collagen Type IV / Q000378:metabolism; D051546:Cyclooxygenase 2; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009836:Oligodendroglia / Q000378:metabolism*; D011180:Postmortem Changes; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D002097:C-Reactive Protein; D019013:CD40 Antigens; D024141:Collagen Type IV; D051546:Cyclooxygenase 2; D006684:HLA-DR Antigens; D018799:Intercellular Adhesion Molecule-1; D007527:Isoenzymes; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C496540:PTGS2 protein, human