Penetrating arterioles are a bottleneck in the perfusion of neocortex

Abstract

Penetrating arterioles bridge the mesh of communicating arterioles on the surface of cortex with the subsurface microvascular bed that feeds the underlying neural tissue. We tested the conjecture that penetrating arterioles, which are positioned to regulate the delivery of blood, are loci of severe ischemia in the event of occlusion. Focal photothrombosis was used to occlude single penetrating arterioles in rat parietal cortex, and the resultant changes in flow of red blood cells were measured with two-photon laser-scanning microscopy in individual subsurface microvessels that surround the occlusion. We observed that the average flow of red blood cells nearly stalls adjacent to the occlusion and remains within 30% of its baseline value in vessels as far as 10 branch points downstream from the occlusion. Preservation of average flow emerges 350 m away; this length scale is consistent with the spatial distribution of penetrating arterioles. We conclude that penetrating arterioles are a bottleneck in the supply of blood to neocortex, at least to superficial layers.blood flow ͉ hemodynamics ͉ ischemia ͉ stroke ͉ two photon

Topological basis for the robust distribution of blood to rodent neocortex

“…6). Consistent with the role of loops in the redistribution of blood from surrounding regions to the center, this area exceeds the estimate of 0.94 mm 2 for the average area of a loop and far exceeds the estimates of 0.13 mm 2 for average area sourced by a penetrating arteriole (35) (Fig. S3) and 0.2 mm 2 for the minimize size of an infarct (17,20).…”

“…As a positive control, we compare these findings with damage caused by the complete loss of flow to a single penetrating arteriole. In this case, the photothrombotic clot was formed in the surface branch of a penetrating arteriole before it descends into the parenchyma (35). Occlusions to penetrating arterioles generated infarctions that were an order of magnitude larger in volume than those to a surface vessel, averaging (n = 6) 0.17 ± 0.03 mm 3 (mean ± SE) (Fig.…”

“…Occlusions were targeted to single pial and penetrating vessels, as described (14,35,50). Animals were allowed to recover and were killed for histological analysis 6 to 8 d after the occlusion.…”

Fine Detail of Neurovascular Coupling Revealed by Spatiotemporal Analysis of the Hemodynamic Response to Single Whisker Stimulation in Rat Barrel Cortex

“…have increased the magnification of our images by a factor of four by developing new procedures to perform 2D-OIS through a stereo microscope. With this system, we have seen a small network of arterioles on the surface of the cortex that lie between the main branches of the middle cerebral artery [as recently shown by Kleinfeld's group (Nishimura et al 2007)]. These arterioles appear to remain dilated after the main branch of the MCA has returned to baseline.…”

Simulation study of brain blood flow regulation by intra-cortical arterioles in an anatomically accurate large human vascular network. Part II: Flow variations induced by global or localized modifications of arteriolar diameters

“…Thus, as pointed out by Harrison et al, 2002, further detailed mapping studies of blood pathways and associated control points are needed to estimate the ultimate spatial resolution of hemodynamic-based functional imaging methods such as fMRI. However, experimental techniques enabling to perform such mapping studies, such as twophoton laser microscopy, are restricted to small fields of view (between 180 × 180 μm 2 and 400 × 400 μm 2 , Hillman et al, 2007;Hutchinson et al, 2006;Nishimura et al, 2007;Chaigneau et al, 2003), typically smaller or of the same order as voxel size in fMRI. Fluid dynamic modeling is a powerful alternative tool for studying blood flow reorganizations at larger scale.…”