Dynamic changes in vascular permeability, cerebral blood volume, vascular density, and size after transient focal cerebral ischemia in rats: evaluation with contrast-enhanced magnetic resonance imaging

J Cereb Blood Flow Metab. 2008 Aug;28(8):1491-501. doi: 10.1038/jcbfm.2008.42. Epub 2008 May 14.

Abstract

Postischemic cerebral blood flow and blood volume changes have been associated with angiogenesis; nevertheless, the spatiotemporal changes in vascular permeability, vascular density, and vessel size have not been investigated. Here we report a prolonged increase in vascular permeability from day 3 to day 21 after ischemia, in particular in the reperfused outer cortical layers and leptomeninges. Increased cerebral blood volume (CBV) was observed from day 3 to day 14, whereas increased blood volume in small vessels, primarily capillaries, was noticed from day 7 to day 14 in the reperfused cortex. An initial decrease in vascular density and a reciprocal increase in vessel size were observed within the reperfused cortex at days 1 and 3 after ischemia. Immunohistological analysis confirmed a similar decrease in microvessel density and an increase in vessel size in vessels with a diameter greater than 30 microm. These large-sized vessels exhibited intense basic fibroblast growth factor and endothelial nitric oxide synthase immunoreactivity, suggesting the growth of collateral vessels. By contrast, a late increase in vascular density was noticed in the reperfused outer cortex at days 14 and 21 after ischemia. Together, these findings suggest that the early phase of CBV increase is likely because of the improvement in collateral circulation, whereas the late phase of CBV increase is attributed to the surge of angiogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Volume*
  • Brain Ischemia / enzymology
  • Brain Ischemia / pathology
  • Brain Ischemia / physiopathology*
  • Capillary Permeability*
  • Carrier Proteins / metabolism
  • Cerebral Cortex / blood supply*
  • Cerebral Cortex / enzymology
  • Cerebral Cortex / pathology
  • Cerebrovascular Circulation*
  • Magnetic Resonance Imaging* / methods
  • Male
  • Microcirculation / physiopathology
  • Neovascularization, Physiologic
  • Rats
  • Rats, Long-Evans
  • Time Factors
  • Ubiquitin-Protein Ligases

Substances

  • Carrier Proteins
  • NOSIP protein, rat
  • Ubiquitin-Protein Ligases