Regional variation in brain capillary density and vascular response to ischemia

Differences in brain neuroarchitecture have been extensively studied and re cent results demonstrated that regional differences in the physiological pr operties of glial cells are equally common. Relatively little is known on t he topographic differences in vascular supply, distribution and density of brain capillaries in different CNS regions. We developed a simple method co nsisting of intravascular injection of fluorescent dyes coupled to immunocy tochemical techniques that allows for simultaneous observation of glia-neur onal-vascular interactions in immersion-fixed brain specimens from small ro dents. This technique permits quantitative evaluation of regional differenc es in glial/neuronal distribution and the study of their relationship to va scular densities. Variations of this technique also allow the detection of abnormal microvasculature (i.e. `leaky' vessels), a useful feature for stud ies of blood-brain barrier function in health and disease. By use of quanti tative confocal microscopy, the three-dimensional geometry of cortical and hippocampal structures revealed remarkable differences in vascularization b etween cortical gray/white matter junction, and hippocampal formation (CAI and CA3 regions). Significant differences were also observed within the sam e investigative region: CA1 was characterized by low capillary density comp ared to neighboring CA3. Following an ischemic insult, CAI vessels had more extensive blood-brain barrier leakage than CA3 vessels. We conclude that i n addition to neuronal and glial heterogeneity, cortical structures are als o endowed with region-specific vascular patterns characterized by distinct pathophysiological responses. (C) 2001 Elsevier Science B.V. All rights res erved.