Neurophotonic Advances for Mechanistic Investigation of the Role of Capillary Dysfunction in Stroke Recovery

ABSTRACT
Neuroimaging methods are invaluable for managing the treatment of stroke patients in the acute phase of guiding
reperfusion and salvaging tissue, and are being used more and more to understand the effect of and ultimately
guide treatments in the chronic phase of functional brain recovery. At least some degree of functional recovery
is widely observed in most patients in the months following stroke. The exact biological mechanism directing this
recovery is under active investigation. BOLD functional Magnetic Resonance Imaging (fMRI) and functional Near
Infrared Spectroscopy (fNIRS), both of which non-invasively measure the vascular response to brain activity, are
valuable tools for longitudinal monitoring of stroke patients during this recovery period. However, these vascular
responses to external stimuli in brain regions damaged by ischemic stroke are almost always altered relative to
that in brain regions contra-lateral to the stroke and to that seen in healthy individuals. It is not known if this
alteration is a reflection of underlying differences in the neuronal function or simply a result of damaged
vasculature altering the vascular response to activity. In other words, we do not know the effect of stroke on
neurovascular coupling and are thus limited in our ability to use these valuable neuroimaging tools to study
functional recovery in stroke survivors. It is known that stroke triggers a prominent vascular reorganization and
neurovascular unit changes in the periinfarct cortex. It is not known whether the efficiency of this vascular
reorganization contributes to the neurophysiological recovery of the periinfarct cortex, and whether it is linked to
the final functional outcome. Further, it is not known whether periinfarct neurovascular unit changes and capillary
flow quality are a simple reflection of underlying neural recovery or can be a primary determinant of subsequent
neural reorganization. Therefore, there is a great need for studies in well-established and properly controlled
preclinical stroke models to evaluate the evolution of the structural and functional aspects of chronic
neurovascular recovery, for a better mechanistic understanding of these biological interactions, and to
understand their prognostic value for predicting behavioral outcomes following stroke. Our aims are designed to
meet these needs by using a novel combination of optical technologies and a preclinical stroke model. We first
establish the utility of the novel technology for longitudinal imaging of stroke. We will then utilize these
approaches to find the association of hemodynamic recovery signatures with capillary flow stalls. Finally, we
investigate mechanistic explanations for the heterogeneity of these changes.

Grant Number: 5R01NS127156-04
NIH Institute/Center: NIH
Principal Investigator: David Boas