Dr. Deane Vascular Barrier Research

My interest in the CNS vascular barriers [blood-brain barrier (BBB) and blood-CSF barrier (choroid plexus, CP)] and CSF in health and disease was reinforced during my Ph.D. training at St. Thomas’ Hospital (London), supervised by Dr. M.B. Segal, an expert on the choroid plexus/CSF secretion. I investigated sugar transport and CSF secretion mechanisms by the choroid plexus. Training on CSF development and mathematical modeling of CSF flow and its dynamics in developing rats was obtained in the lab of Dr. Hazel Jones (University of Hull). Concepts of BBB dysfunction were further developed during my postdoctoral fellowship at King’s college, in the lab of Prof. M. B. Bradbury, a BBB expert, where we elucidated the mechanism of lead transport across the BBB and into CSF across the CP.

In addition, we were the first to show a functional significance of albumin clearance from CSF to blood via the cervical lymphatic system (1980). After a period (1987-2002) of lecturing/Couse Development as a Program Director (Pathway Leader), at the University of Greenwich, I returned to active research in 2002. I joined Dr. Berislav Zlokovic, at the University of Rochester (NY, USA), one of the leading neurovascular experts who was conducting pioneering work on the vascular concept of AD and neurodegeneration. Here I used state-of-the-art techniques to study the role of the BBB and brain clearance in neurodegeneration. We investigated the mechanisms of Aβ and apoE isoform transport into and out of the brain using radio-labeled Aβ and apoEs, or ELISA and Western bot analysis. We also analyzed BBB permeability from in vivo time-lapse multiphoton microscopy images of different size dextran tracers, and from radio-labeled tracers, and convective flow of interstitial fluid in brain clearance.

In 2012, I collaborated with Dr. Maiken Nedergaard (Co-Director, Center for Translational Neuromedicine (CTN)), an expert on astrocytes, who was reinvestigating the CSF/ISF exchange and coined the term glymphatic system for this process. In 2017, I joined the Department of Neuroscience and remain in the Department of Neurosurgery. Thus, my long and extensive experience in the blood/brain/CSF areas puts me in a unique position to objectively complete these interesting studies. Completion of the proposed studies will lead to a better understanding on the role of CSF in protein clearance that may lead to the development of new approaches to restore CSF flow and thus, brain clearance. This may slow the on-set of the AD cognitive decline and the pending AD tsunami.