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

Chris B Schaffer,David Kleinfeld,Patrick D Lyden,Lee F Schroeder,Ford F Ebner,Nozomi Nishimura,Beth Friedman,Philbert S Tsai,Maurizio Corbetta

doi:10.1371/journal.pbio.0040022

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.

Highlights

Normal brain function requires adequate levels of blood flow to ensure the delivery of oxygen and nutrients to cells and to facilitate the removal of metabolites and heat
A high degree of redundancy in the surface arteriole network is apparent, with anastomoses formed between vessels from both the same and different middle cerebral artery (MCA) branches (Figure 1B)
In which the laser focus is repetitively scanned along the axis of each vessel (Figure 1C), are used to form a space–time image in which the non-fluorescent red blood cell (RBC) are represented as dark streaks (Figure 1D) [14,15,23,24]

Summary

Introduction

Normal brain function requires adequate levels of blood flow to ensure the delivery of oxygen and nutrients to cells and to facilitate the removal of metabolites and heat. At the level of the supply to the brain, a pair of ‘‘communicating’’ arteries connects the carotid arteries to form the Circle of Willis. This loop is known to ensure a substantial level of fault tolerance to an occlusion of one of the member vessels [3]. At the level of cerebral cortex, the branches of each cerebral artery form the artery’s own network of communicating arterioles on the surface of its cortical territory [4]. This network, in turn, gives rise to arterioles that plunge into the cortex and branch into the capillary bed. Previous efforts to test this hypothesis, as well as the more general issue of the relationship between network topology and compensatory flow after an occlusion [3,9,10], have been hampered by a lack of methodology in which small vascular occlusions can be precisely targeted in time and space and in which flow can be quantified throughout multiple neighboring branches in a network

Methods

Results

Conclusion