Vascular integrin immunoreactivity is selectively lost on capillaries during rat focal cerebral ischemia and reperfusion

Brain Res. 2008 Jan 16;1189:189-97. doi: 10.1016/j.brainres.2007.10.085. Epub 2007 Nov 7.

Abstract

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.

MeSH terms

  • Animals
  • Blood-Brain Barrier / metabolism
  • Blood-Brain Barrier / pathology
  • Blood-Brain Barrier / physiopathology
  • Brain / blood supply
  • Brain / physiopathology
  • Brain Edema / metabolism
  • Brain Edema / physiopathology
  • Brain Ischemia / metabolism*
  • Brain Ischemia / pathology
  • Brain Ischemia / physiopathology
  • Capillaries / metabolism*
  • Capillaries / pathology
  • Capillaries / physiopathology
  • Cerebral Arteries / metabolism*
  • Cerebral Arteries / pathology
  • Cerebral Arteries / physiopathology
  • Cerebral Hemorrhage / metabolism
  • Cerebral Hemorrhage / physiopathology
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Immunohistochemistry
  • Integrin alpha1 / metabolism
  • Integrin alpha6 / metabolism
  • Integrin beta1 / metabolism
  • Integrins / immunology
  • Integrins / metabolism*
  • Male
  • Pericytes / metabolism
  • Pericytes / pathology
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / metabolism*
  • Reperfusion Injury / pathology
  • Reperfusion Injury / physiopathology
  • Serum Albumin / metabolism

Substances

  • Integrin alpha1
  • Integrin alpha6
  • Integrin beta1
  • Integrins
  • Serum Albumin