Two-Photon Imaging of Cortical Surface Microvessels Reveals a Robust Redistribution in Blood Flow after Vascular Occlusion

Department of Physics, University of California San Diego, La Jolla, California, USA.
PLoS Biology (Impact Factor: 9.34). 03/2006; 4(2):e22. DOI: 10.1371/journal.pbio.0040022
Source: PubMed

ABSTRACT A highly interconnected network of arterioles overlies mammalian cortex to route blood to the cortical mantle. Here we test if this angioarchitecture can ensure that the supply of blood is redistributed after vascular occlusion. We use rodent parietal cortex as a model system and image the flow of red blood cells in individual microvessels. Changes in flow are quantified in response to photothrombotic occlusions to individual pial arterioles as well as to physical occlusions of the middle cerebral artery (MCA), the primary source of blood to this network. We observe that perfusion is rapidly reestablished at the first branch downstream from a photothrombotic occlusion through a reversal in flow in one vessel. More distal downstream arterioles also show reversals in flow. Further, occlusion of the MCA leads to reversals in flow through approximately half of the downstream but distant arterioles. Thus the cortical arteriolar network supports collateral flow that may mitigate the effects of vessel obstruction, as may occur secondary to neurovascular pathology.

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Available from: Nozomi Nishimura, Sep 26, 2015
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    • "Such data may be used to predict local vulnerability to vascular disruptions, but insight from the data with respect to stroke is still in progress. It is conceivable that interactive computer models could be made of the effects of clots in animal models to validate experiments (Blinder et al., 2010; Schaffer et al., 2006). Future work will be guided by seminal quantitative studies that have focused on rat barrel cortex (Blinder et al., 2013). "
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    ABSTRACT: Connections between neurons are affected within 3 min of stroke onset by massive ischemic depolarization and then delayed cell death. Some connections can recover with prompt reperfusion; others associated with the dying infarct do not. Disruption in functional connectivity is due to direct tissue loss and indirect disconnections of remote areas known as diaschisis. Stroke is devastating, yet given the brain's redundant design, collateral surviving networks and their connections are well-positioned to compensate. Our perspective is that new treatments for stroke may involve a rational functional and structural connections-based approach. Surviving, affected, and at-risk networks can be identified and targeted with scenario-specific treatments. Strategies for recovery may include functional inhibition of the intact hemisphere, rerouting of connections, or setpoint-mediated network plasticity. These approaches may be guided by brain imaging and enabled by patient- and injury-specific brain stimulation, rehabilitation, and potential molecule-based strategies to enable new connections.
    Neuron 09/2014; 83(6):1354-1368. DOI:10.1016/j.neuron.2014.08.052 · 15.05 Impact Factor
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    • "The cause of chronic electrode degradation is thought to arise either from a neuroinflammatory response or from biomaterial failure [19–22]. Cortical vessels can undergo extensive re-modeling in response to injury, as demonstrated in studies of stroke and traumatic brain injury [23–25]. Change to the vascular around an implanted electrode has the potential to be an early indicator or biomarker of signal degradation. "
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    ABSTRACT: Speckle variance optical coherence angiography (OCA) was used to characterize the vascular tissue response from craniotomy, window implantation, and electrode insertion in mouse motor cortex. We observed initial vasodilation ~40% greater than original diameter 2-3 days post-surgery (dps). After 4 weeks, dilation subsided in large vessels (>50 µm diameter) but persisted in smaller vessels (25-50 µm diameter). Neovascularization began 8-12 dps and vessel migration continued throughout the study. Vasodilation and neovascularization were primarily associated with craniotomy and window implantation rather than electrode insertion. Initial evidence of capillary re-mapping in the region surrounding the implanted electrode was manifest in OCA image dissimilarity. Further investigation, including higher resolution imaging, is required to validate the finding. Spontaneous lesions also occurred in many electrode animals, though the inception point appeared random and not directly associated with electrode insertion. OCA allows high resolution, label-free in vivo visualization of neurovascular tissue, which may help determine any biological contribution to chronic electrode signal degradation. Vascular and flow-based biomarkers can aid development of novel neural prostheses.
    Biomedical Optics Express 08/2014; 5(8). DOI:10.1364/BOE.5.002823 · 3.65 Impact Factor
    • "First, TEM and immunofluorescence assays for TJ morphology changes agree with our two-photon imaging data, arguing against a limitation in detecting early TJ defects by two-photon imaging. Second, while t-MCAO typically results in infarction of the basal ganglia with less severe deficits in the cerebral cortex, due to a compensatory circulatory system from surface-communicating arterioles (Schaffer et al., 2006), the parietal cortex area imaged was located within the stroke or penumbra region based on three criteria: (1) early changes in endothelial caveolae and the rates of transcytosis visualized by TEM and tracer uptake, respectively; "
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    ABSTRACT: Brain endothelial cells form a paracellular and transcellular barrier to many blood-borne solutes via tight junctions (TJs) and scarce endocytotic vesicles. The blood-brain barrier (BBB) plays a pivotal role in the healthy and diseased CNS. BBB damage after ischemic stroke contributes to increased mortality, yet the contributions of paracellular and transcellular mechanisms to this process in vivo are unknown. We have created a transgenic mouse strain whose endothelial TJs are labeled with eGFP and have imaged dynamic TJ changes and fluorescent tracer leakage across the BBB in vivo, using two-photon microscopy in the t-MCAO stroke model. Although barrier function is impaired as early as 6 hr after stroke, TJs display profound structural defects only after 2 days. Conversely, the number of endothelial caveolae and transcytosis rate increase as early as 6 hr after stroke. Therefore, stepwise impairment of transcellular followed by paracellular barrier mechanisms accounts for the BBB deficits in stroke.
    Neuron 04/2014; 82(3). DOI:10.1016/j.neuron.2014.03.003 · 15.05 Impact Factor
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