Abstract
Microvascular disease leads to alterations of cerebral vasculature including the formation of microembolic (ME) strokes. Though ME are associated with changes in mood and the severity and progression of cognitive decline, the effect of ME strokes on cerebral microstructure and its relationship to behavioral endpoints is unknown. Here, we used adult and aged male rats to test the hypotheses that ME lesions result in subtle changes to white and gray matter integrity as detected by high-throughput diffusion tensor imaging (DTI) and that these structural disruptions correspond to behavioral deficits. Two weeks post-surgery, aged animals showed depressive-like behaviors in the sucrose consumption test in the absence of altered cerebral diffusivity as assessed by ex-vivo DTI. Furthermore, DTI indices did not correlate with the degree of behavioral disruption in aged animals or in a subset of animals with observed tissue cavitation and subtle DTI alterations. Together, data suggest that behavioral deficits are not the result of damage to brain regions or white matter tracts, rather the activity of other systems may underlie functional disruption and recovery.
Highlights
Microvascular pathology is common in the aged population and the incidence of microvascular disease is growing [1]
Our results demonstrate that the induction of diffuse microsphere lesions is not sufficient to produce lasting alterations to metrics of diffusion tensor imaging (DTI) in adult or aged animals eighteen days following the procedure
High-throughput ex vivo DTI analysis of ME-treated aged rodent brains revealed no changes in tract strength or gray matter tissue integrity in any brain region measured
Summary
Microvascular pathology is common in the aged population and the incidence of microvascular disease is growing [1]. Small vessel pathology, including within the context of microvascular pathology, and microvascular events (e.g. thickening of arterial walls, microvascular lesions, and microembolic strokes [2,3]) are known contributors to depressive behaviors late in life [4,5,6,7,8,9,10], and have been implicated in the progression of cognitive impairment and Alzheimer’s disease [11,12] Despite these links and the high correlation between microvascular disruption and behavioral deficits, the mechanisms behind this relationship remain a topic of debate [13]. Because ME lesions are typically detected following a larger ischemic event or after death, preventative measures and treatment strategies are greatly hindered
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