Vascular integrin immunoreactivity is selectively lost on capillaries during rat focal cerebral ischemia and reperfusion.
The alpha1-integrin cell adhesion molecules, the principal endothelial receptors for basal lamina (BL) components disappear during transient ischemia. The current study investigated the localization of integrins, the time dependency and vessel size selectivity in the normal rat brain before and after 3 h of cerebral ischemia (I3) and reperfusion (R). Additionally we looked for a correlation to the amount of extravasation and hemorrhage. In the normal brain, there was a clear immunoreactivity for the alpha1, alpha6, and beta1 integrins on the endothelial perivascular cells. After I3 followed by variable reperfusion intervals of 0, 9, and 24 h (R0, R9 and R24; respectively), the number of vessels and staining intensity indicating immunoreactivity in the ischemic area were compared with the contralateral side. The number of the beta1-immunoreactive capillaries was steadily decreasing with the reperfusion time: -12+/-5%, -15+/-7% and -43+/-8% at I3R0, I3R9 and I3R24 (all p<0.05). The beta1-staining intensity decreased homogeneously to -21% at I3R24 (p<0.05). Vascular staining for alpha1 was affected similarly. Interestingly, the alpha6-positive arterioles/venules were also reduced by -21% at I3R24 (p<0.05) in a diameter-selective way on vessels with diameters larger than 15 mum. The correlated break-down of the blood-brain-barrier was demonstrated by the significant rise of the extravasation of BSA from the perfusion solution as well as the increased hemorrhage after MCAO/R (hemoglobin: 103+/-4% versus 330+/-17%; BSA 101+/-3% versus 132+/-9% in I0R0 and I3R24, respectively). The prominent capillary vulnerability contributes significantly to the impairment of the microvascular integrity and after ischemia and reperfusion.
Burggraf
Dorothe
D
Department of Neurology, Ludwig-Maximilians University, Klinikum Grosshadern, Marchioninistr. 15, 81377 Munich, Germany.
Trinkl
Andreas
A
Burk
Jan
J
Martens
Helge K
HK
Dichgans
Martin
M
Hamann
Gerhard F
GF
D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000098:blood supply / Q000503:physiopathology; D001929:Brain Edema / Q000378:metabolism / Q000503:physiopathology; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002196:Capillaries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002536:Cerebral Arteries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002543:Cerebral Hemorrhage / Q000378:metabolism / Q000503:physiopathology; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D039423:Integrin alpha1 / Q000378:metabolism; D039503:Integrin alpha6 / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D016023:Integrins / Q000276:immunology / Q000378:metabolism*; D008297:Male; D020286:Pericytes / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D012709:Serum Albumin / Q000378:metabolism
D039423:Integrin alpha1; D039503:Integrin alpha6; D019012:Integrin beta1; D016023:Integrins; D012709:Serum Albumin