Spatial flow-volume dissociation of the cerebral microcirculatory response to mild hypercapnia

Elizabeth B. Hutchinson, Bojana Stefanovic, Alan P. Koretsky, Afonso C. Silva

Research output: Contribution to journalArticlepeer-review

103 Scopus citations


The spatial and temporal response of the cerebral microcirculation to mild hypercapnia was investigated via two-photon laser-scanning microscopy. Cortical vessels, traversing the top 200 μm of somatosensory cortex, were visualized in α-chloralose-anesthetized Sprague-Dawley rats equipped with a cranial window. Intraluminal vessel diameters, transit times of fluorescent dextrans and red blood cells (RBC) velocities in individual capillaries were measured under normocapnic (PaCO2 = 32.6 ± 2.6 mm Hg) and slightly hypercapnic (PaCO2 = 45 ± 7 mm Hg) conditions. This gentle increase in PaCO2 was sufficient to produce robust and significant increases in both arterial and venous vessel diameters, concomitant to decreases in transit times of a bolus of dye from artery to venule (14%, P < 0.05) and from artery to vein (27%, P < 0.05). On the whole, capillaries exhibited a significant increase in diameter (16 ± 33%, P < 0.001, n = 393) and a substantial increase in RBC velocities (75 ± 114%, P < 0.001, n = 46) with hypercapnia. However, the response of the cerebral microvasculature to modest increases in PaCO2 was spatially heterogeneous. The maximal relative dilatation (range: 5-77%; mean ± SD: 25 ± 34%, P < 0.001, n = 271) occurred in the smallest capillaries (1.6 μm-4.0 μm resting diameter), while medium and larger capillaries (4.4 μm-6.8 μm resting diameter) showed no significant changes in diameter (P > 0.08, n = 122). In contrast, on average, RBC velocities increased less in the smaller capillaries (39 ± 5%, P < 0.002, n = 22) than in the medium and larger capillaries (107 ± 142%, P < 0.003, n = 24). Thus, the changes in capillary RBC velocities were spatially distinct from the observed volumetric changes and occurred to homogenize cerebral blood flow along capillaries of all diameters.

Original languageEnglish (US)
Pages (from-to)520-530
Number of pages11
Issue number2
StatePublished - Aug 15 2006
Externally publishedYes


  • Brain
  • Cerebral blood flow
  • Hypercapnia
  • Red blood cell velocity
  • Two-photon microscopy

ASJC Scopus subject areas

  • Neurology
  • Cognitive Neuroscience


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