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


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.

Download full-text


Available from: Nozomi Nishimura
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    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.
    Full-text · Article · Sep 2014 · Neuron
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    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.
    Full-text · Article · Aug 2014 · Biomedical Optics Express
  • Source
    • "In the present study we developed a protocol for inducing focal ischemic stroke in fully awake mice using the photothrombotic method (Watson et al., 1985). An advantage of this approach is that ischemic stroke can be targeted to a specific brain region or artery (Nishimura et al., 2006; Schaffer et al., 2006; Sigler et al., 2008) without extensive surgical training or invasive procedures. Here we show that not only can isoflurane anesthesia reduce the extent of ischemic damage after stroke, but it can mask the protective effects of a stroke therapy. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Anesthetics such as isoflurane are commonly used to sedate experimental animals during the induction of stroke. Since these agents are known to modulate synaptic excitability, inflammation and blood flow, they could hinder the development and discovery of new neuroprotection therapies. To address this issue, we developed a protocol for inducing photothrombotic occlusion of cerebral vessels in fully conscious mice and tested two potential neuroprotectant drugs (a GluN2B or α4β2 nicotinic receptor antagonist). Our data show in vehicle treated mice that just 20 min of exposure to isoflurane during stroke induction can significantly reduce ischemic cortical damage relative to mice that were awake during stroke. When comparing potential stroke therapies, none provided any level of neuroprotection if the stroke was induced with anesthesia. However, if mice were fully conscious during stroke, the α4β2 nicotinic receptor antagonist reduced ischemic damage by 23% relative to vehicle treated controls, whereas the GluN2B antagonist had no significant effect. These results suggest that isoflurane anesthesia can occlude the benefits of certain stroke treatments and warrant caution when using anesthetics for pre-clinical testing of neuroprotective agents.
    Full-text · Article · Apr 2014 · Frontiers in Neuroenergetics
Show more