Abstract
Neuronal and vascular brain components are interrelated morphologically, physiologically and developmentally. Due to this close interrelationship, it is often difficult to understand the cause and effect relationship between neuronal vs. vascular dysfunction and pathology. This review will discuss four of the more promising recent developments for detecting vascular pathology, and will compare them with the labeling pattern seen with markers of glial and neuronal pathology; following exposure to well characterized neurotoxicants. To detect the vascular dysfunction in the brain, we recently developed a Fluoro-Turquoise gelatin conjugate (FT-gel), a fluorescent probe that helps to delineate between healthy vs. sclerotic vessels. Similarly, we have investigated the potential for Fluoro-Gold to label in vivo all the endothelial cells in the brain as they co-localize with RECA, an endothelial cell marker. We have also developed Amylo-Glo, a fluorescent tracer that can detect neurotoxic A-beta aggregates in the brain. In this article, we will discuss the potential use of these novel histochemical markers to study the neurotoxicant induced brain. We will also discuss neurovascular strategies that may offer novel therapeutic opportunities for neurodegenerative disorders.
Highlights
Vasculature in the brain plays a crucial role in maintaining homeostatic conditions
The association of pericytes with endothelial cells or astrocytes is critical since loss of the contact between them or pericyte dysfunction can lead to development of diseases such as stroke [30], multiple sclerosis [31,32] and brain tumors [33,34]
Since pericytes are key components of the neurovascular units (NVU) of the brain and help mediate vascular function [18,35], understanding the mechanism by which pericytes interact with other components of the NVU as well as other factors that result in dysfunctional pericytes in pathological conditions, are important
Summary
Vasculature in the brain plays a crucial role in maintaining homeostatic conditions. In normal conditions, the human brain receives around 20% of the cardiac output. Hyperemia that denotes the link between neuronal activity and regional blood flow (CBF) play an important role in neurovascular disease Neurodegenerative disorders such as in AD, Parkinson’s disease (PD) and Amyotrophic lateral sclerosis (ALS) are associated with microvascular dysfunction and degeneration in the brain, neurovascular disintegration, defective BBB function or vascular elements [7,8,9]. In these neurodegenerative conditions, blood flow to the brain diminishes and subsequently reduces the supply of oxygen, energy and nutrients., this kind of deficit could impair the ability of the BBB to clear the toxic molecules that accumulate or are deposited in the non-neuronal cells or neurons. In this review we will elaborate how our novel histochemical tracers have been useful to delineate the difference in microvascular morphology following exposures to different neurotoxins
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