Neurological disorders, such as stroke and brain tumors, affect up to one billion people worldwide. Finding new treatments and understanding how these neurological disorders develop requires a better understanding of the complex interactions that occur in the brain. Our lab’s primary interest is studying interactions between brain vasculature (blood vessels) and the nervous system (glial cells and neurons). By combining electrophysiology and in vivo imaging with genetic methods, we hope to determine how the brain builds the gliovascular and neurovascular network during development and how this network can be damaged as a result of a stroke and then repaired.
Although pericytes are located along vessels in both the central nervous system and other organs, astrocytic endfeet cover only the vasculature in the central nervous system. It remains unclear whether there are subtypes of pericytes in blood vessels and, if so, what their functions are in the brain. There is also little information available about how different subtypes of pericytes interact with glial cells or neurons in the brain.
To answer these questions, we will introduce techniques including electrophysiology and in vivo imaging into the study of brain pericytes. The goal is to isolate pericytes from several sources (arterioles, precapillaries, capillaries, postcapillaries and venules) to characterize the molecular and cellular profile of pericytes from these different locations. We have already established an electrophysiological technique to record individual pericytes within different segments of blood vessels in acutely isolated brain slices.
Formation of Gliovascular Interface
Glial cells constitute approximately half of the cells in the human brain. As the largest population of glial cells, astrocytes are crucial for the survival and function of neurons. Together with brain vasculature, astrocytic endfeet form an intricate structure called the gliovascular interface. This interface is critical for the transport of glucose from the blood to neurons, the regulation of cerebral blood flow and the maintenance of the blood-brain barrier. Detachment of astrocytic endfeet from the vascular membrane is responsible for brain edema and results in neurodegeneration. Restoring this function after stroke is critical to improving functional brain recovery in patients.
How the gliovascular interface forms and develops is unclear. We are studying the cellular and molecular mechanisms for interactions between brain vasculature and astrocytes with genetic manipulation and time-lapse slice or in vivo imaging.