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: 9.67). 02/2007; 104(1):365-70. DOI: 10.1073/pnas.0609551104
Source: PubMed


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, Sep 29, 2015
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    • "Two-photon microscopy [9] was the first technology to perform cellular imaging at depths of several hundred µm in the living brain, and has significantly impacted neuroscience research over the past 15 years. Recently, two-photon microscopy has emerged as an in vivo method to investigate changes in hemodynamics [10]–[12] and synaptic networks [13]–[16] in ischemic stroke and spreading depression [17], [18]. However, while two-photon microscopy achieves subcellular spatial resolution, the imaging speed, penetration depth, and field-of-view are limited. "
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    ABSTRACT: Progress in experimental stroke and translational medicine could be accelerated by high-resolution in vivo imaging of disease progression in the mouse cortex. Here, we introduce optical microscopic methods that monitor brain injury progression using intrinsic optical scattering properties of cortical tissue. A multi-parametric Optical Coherence Tomography (OCT) platform for longitudinal imaging of ischemic stroke in mice, through thinned-skull, reinforced cranial window surgical preparations, is described. In the acute stages, the spatiotemporal interplay between hemodynamics and cell viability, a key determinant of pathogenesis, was imaged. In acute stroke, microscopic biomarkers for eventual infarction, including capillary non-perfusion, cerebral blood flow deficiency, altered cellular scattering, and impaired autoregulation of cerebral blood flow, were quantified and correlated with histology. Additionally, longitudinal microscopy revealed remodeling and flow recovery after one week of chronic stroke. Intrinsic scattering properties serve as reporters of acute cellular and vascular injury and recovery in experimental stroke. Multi-parametric OCT represents a robust in vivo imaging platform to comprehensively investigate these properties.
    PLoS ONE 08/2013; 8(8):e71478. DOI:10.1371/journal.pone.0071478 · 3.23 Impact Factor
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    • "Physiologically, the intravascular oxygen tensions may indicate extreme tissue hypoxia surrounding the vessel. Microcirculation studies observing substantial cell death in the cortical layers around single descending arterioles following occlusion may have sampled similar latent branching vessels [24,30]. The inherent sensitivity of the phosphorescent quenching oximetry technique noted in Figs. "
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    ABSTRACT: Occlusions in single cortical microvessels lead to a reduction in oxygen supply, but this decrement has not been able to be quantified in three dimensions at the level of individual vessels using a single instrument. We demonstrate a combined optical system using two-photon phosphorescence lifetime and fluorescence microscopy (2PLM) to characterize the partial pressure of oxygen (pO2) in single descending cortical arterioles in the mouse brain before and after generating a targeted photothrombotic occlusion. Integrated real-time Laser Speckle Contrast Imaging (LSCI) provides wide-field perfusion maps that are used to monitor and guide the occlusion process while 2PLM maps changes in intravascular oxygen tension. We present the technique’s utility in highlighting the effects of vascular networking on the residual intravascular oxygen tensions measured after occlusion in three dimensions.
    Biomedical Optics Express 07/2013; 4(7):1061-1073. DOI:10.1364/BOE.4.001061 · 3.65 Impact Factor
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    • "In addition to visualizing vascular topology, we measured the diameter and blood flow speed and direction in individual vessels, as described previously [26]. For hemorrhages, we targeted cortical penetrating arterioles (PA), i.e. arterioles that branch from the surface arteriole network and dive into the brain to feed capillary beds [27]. These vessels were identified by tracing through the vascular network from readily-identifiable surface arterioles and we confirmed they were penetrating arterioles by checking that the blood flow direction was into the brain. "
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    ABSTRACT: Tissue plasminogen activator (tPA) is the only FDA-approved treatment for reperfusing ischemic strokes. But widespread use of tPA is still limited by fears of inadvertently administering tPA in patients with intracerebral hemorrhage (ICH). Surprisingly, however, the assumption that tPA will worsen ICH has never been biologically tested. Here, we assessed the effects of tPA in two models of ICH. In a mouse model of collagenase-induced ICH, hemorrhage volumes and neurological deficits after 24 hrs were similar in saline controls and tPA-treated mice, whereas heparin-treated mice had 3-fold larger hematomas. In a model of laser-induced vessel rupture, tPA also did not worsen hemorrhage volumes, while heparin did. tPA is known to worsen neurovascular injury by amplifying matrix metalloproteinases during cerebral ischemia. In contrast, tPA did not upregulate matrix metalloproteinases in our mouse ICH models. In summary, our experimental data do not support the assumption that intravenous tPA has a deleterious effect in acute ICH. However, due to potential species differences and the inability of models to fully capture the dynamics of human ICH, caution is warranted when considering the implications of these findings for human therapy.
    PLoS ONE 02/2013; 8(2):e54203. DOI:10.1371/journal.pone.0054203 · 3.23 Impact Factor
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