Novel cytogenic and neurovascular niches due to blood-brain barrier compromise in the XXXX brain.

@entity1118 @entity1 @entity158 @entity130
BACKGROUND: The mechanisms by which painful @entity130 are linked to the multitude of @entity158 and neuroplastic changes in the brain remain poorly understood. Here we propose a model that relies on epi-neuronal communication through the vascular system to effect various brain structures. Specifically, we hypothesize that the differential vulnerability of the blood-brain barrier (BBB) in different brain regions is associated with region-specific neuroplastic and neurovascular changes that are in turn associated with particular @entity158 . PRESENTATION OF THE HYPOTHESIS: We will present our hypothesis by focusing on two main points: (A) @entity1118 ( @entity1118 ) is associated with differential BBB compromise. (B) Circulating mediators leaking through the BBB create cytogenic and neovascular niches associated with @entity158 -related co-morbidities. TESTING THE HYPOTHESIS: Pre-clinically, our hypothesis can be tested by observing, in parallel, BBB compromise, (neo)vascularization, neurogenesis, and their co-localization in @entity158 models using imaging, microscopy, biochemical and other tools. Furthermore, the BBB can be experimentally damaged in specific brain regions, and the consequences of those lesions studied on nociception and associated comorbidities. Recently developed imaging techniques allow the analysis of blood brain barrier integrity in @entity1 providing a route for translation of the laboratory findings. Though perhaps more limited, post-mortem examination of brains with available @entity158 histories constitutes a second approach to addressing this hypothesis. IMPLICATIONS OF THE HYPOTHESIS: Understanding changes in BBB permeability in @entity1118 conditions has clear implications both for understanding the pathogenesis of @entity1118 and for the design of novel treatments to prevent @entity1118 and its consequences. More broadly, this hypothesis may help us to understand how peripheral @entity130 impact the brain via mechanisms other than commonly studied efferent sensory pathways.
