Penetrating arterioles are a bottleneck in the perfusion of neocortex. Proc Natl Acad Sci U S A

Department of Physics, University of California at San Diego, La Jolla, CA 92093, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 02/2007; 104(1):365-70. DOI: 10.1073/pnas.0609551104
Source: PubMed

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 mum 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.

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Available from: Nozomi Nishimura, Aug 25, 2015
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    • "If we restrict our analysis to the identification of the last neuronal relays, i.e., interneurons and pyramids, many ex vivo experiments from our group have clearly demonstrated that distinct subclasses of interneurons containing VIP, NOS, SOM, and NPY control directly the tone of the smooth muscles of the arterioles (Cauli et al., 2004; Rancillac et al., 2006). Indeed, smooth muscles of the penetrating arterioles are ideally localized to be the main regulators of blood flow and pressure in the cortical cortex (Hillman, 2007; Nishimura et al., 2007). This regulation occurs at the precapillary level through sphincters that are involved in a localized control of capillary tone (Peppiatt et al., 2006; Attwell et al., 2010; Hamilton et al., 2010). "
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    ABSTRACT: Although it is know since more than a century that neuronal activity is coupled to blood supply regulation, the underlying pathways remains to be identified. In the brain, neuronal activation triggers a local increase of cerebral blood flow (CBF) that is controlled by the neurogliovascular unit composed of terminals of neurons, astrocytes, and blood vessel muscles. It is generally accepted that the regulation of the neurogliovascular unit is adjusted to local metabolic demand by local circuits. Today experimental data led us to realize that the regulatory mechanisms are more complex and that a neuronal system within the brain is devoted to the control of local brain-blood flow. Recent optogenetic experiments combined with functional magnetic resonance imaging have revealed that light stimulation of neurons expressing the calcium binding protein parvalbumin (PV) is associated with positive blood oxygen level-dependent (BOLD) signal in the corresponding barrel field but also with negative BOLD in the surrounding deeper area. Here, we demonstrate that in acute brain slices, channelrhodopsin-2 (ChR2) based photostimulation of PV containing neurons gives rise to an effective contraction of penetrating arterioles. These results support the neurogenic hypothesis of a complex distributed nervous system controlling the CBF.
    Frontiers in Pharmacology 06/2012; 3:105. DOI:10.3389/fphar.2012.00105 · 3.80 Impact Factor
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    • "This suggests that, the deeper a vascular segment is situated, the larger is the number of feeding arteries and so the possible compensation. In consequence, the drastic effects on blood speed observed in several generations of branches downstream of a clotobstructed penetrating arteriole, when an experimental approach was used (Nishimura et al., 2007), may not apply to the whole vessel network, since the experimental exploration is technically limited to the upper part of the cortex. Interestingly, infarct volumes generated by occlusion of intra-cortical arterioles do not present a regular cylindrical shape around the damaged arteriole, but a rather conical shape having its base in the upper cortical layers (Blinder et al., 2010). "
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    ABSTRACT: Vascular domains have been described as being coupled to neuronal functional units enabling dynamic blood supply to the cerebral cyto-architecture. Recent experiments have shown that penetrating arterioles of the grey matter are the building blocks for such units. Nevertheless, vascular territories are still poorly known, as the collection and analysis of large three-dimensional micro-vascular networks are difficult. By using an exhaustive reconstruction of the micro-vascular network in an 18 mm(3) volume of marmoset cerebral cortex, we numerically computed the blood flow in each blood vessel. We thus defined arterial and venular territories and examined their overlap. A large part of the intracortical vascular network was found to be supplied by several arteries and drained by several venules. We quantified this multiple potential to compensate for deficiencies by introducing a new robustness parameter. Robustness proved to be positively correlated with cortical depth and a systematic investigation of coupling maps indicated local patterns of overlap between neighbouring arteries and neighbouring venules. However, arterio-venular coupling did not have a spatial pattern of overlap but showed locally preferential functional coupling, especially of one artery with two venules, supporting the notion of vascular units. We concluded that intra-cortical perfusion in the primate was characterised by both very narrow functional beds and a large capacity for compensatory redistribution, far beyond the nearest neighbour collaterals.
    NeuroImage 04/2012; 62(1):408-17. DOI:10.1016/j.neuroimage.2012.04.030 · 6.36 Impact Factor
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    • "However, the parameters of pressure/flow were not tightly controlled. The effects of flow on vascular reactivity has also been evaluated under in vivo conditions (Takano et al. 2006; Nishimura et al. 2007), in larger vessels (Shapiro et al. 1971) as well as in excised parenchymal arterioles of greater diameters (>60 μm) (Shimoda et al. 1996, 1998; Bryan et al. 2001a; Horiuchi et al. 2001, 2002; Cipolla et al. 2004, 2009; Cipolla & Bullinger, 2008; Toth et al. 2011). As the effects of flow on vessel diameter are dependent on the calibre of the vessel, understanding the effects of flow on pre-capillary parenchymal arterioles in situ is essential, and forms the basis for the development of this novel experimental approach. "
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    ABSTRACT: An understanding of the signalling events underlying neurovascular coupling mechanisms in the brain is a crucial step in the development of novel therapeutic approaches for the treatment of cerebrovascular-associated disorders. In this study we present an enhanced in vitro brain slice preparation from male Wistar rat cortical slices that incorporates haemodynamic variables (flow and pressure) into parenchymal arterioles resulting in the development of myogenic tone (28% from maximum dilatation). Moreover, we characterized flow-induced vascular responses, resulting in various degrees of vasoconstrictions and the response to 10 mM K(+) or astrocytic activation with the mGluR agonist, t-ACPD (100 μM), resulting in vasodilatations of 33.6±4.7% and 38.6±4.6%, respectively. Using fluorescence recovery, we determined perfusate velocity to calculate diameter changes under different experimental pH conditions. Using this approach, we demonstrate no significant differences between diameter changes measured using videomicroscopy or predicted from the velocity values obtained using fluorescence recovery after photobleaching. The model is further validated by demonstrating our ability to cannulate arterioles in two brain regions (cortex and supraoptic nucleus of the hypothalamus). Altogether, we believe this is the first study demonstrating successful cannulation and perfusion of parenchymal arterioles while monitoring/estimating luminal diameter and pressure under conditions where flow rates are controlled.
    The Journal of Physiology 02/2012; 590(Pt 7):1757-70. DOI:10.1113/jphysiol.2011.222778 · 4.54 Impact Factor
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