2020 Barriers of the CNS GRC/GRS

Project Summary / Abstract This proposal requests support for partial funding of the 2020 ?Barriers of the Central Nervous System (CNS)? GRC and GRS that will be held at Colby Sawyer College, New Hampshire, on June 13-14, 2020 (GRS) and June 14-19, 2020 (GRC). The overall goal of this international conference is to improve understanding of the highly complex cellular and molecular mechanisms regulating the function of the endothelial (e.g., blood-brain barrier (BBB) or neurovascular unit (NVU)) and epithelial (e.g., blood-CSF barrier (BCSFB) and arachnoid) brain barriers in development, maintenance and disease. The 2020 meetings will achieve this goal by covering major aspects of CNS barrier sciences and by making a special translational effort to include novel methods of drug delivery to the CNS, including focused ultrasound, convection- enhanced delivery (CED), delivery of macromolecules (such as antibodies and siRNA), nanotechnology-based methods and how interstitial flow influences drug distribution in the CNS. Moreover, we have a session on in vitro models of the BBB and how these may be employed to examine drug delivery and BBB (NVU) development and regulation. This interdisciplinary, highly translational knowledge exchange will be fostered by invited talks, daily poster presentations and ample time for non-structured scientific discussions amongst participants. The program will start with a keynote session addressing the role of the brain barriers in drug delivery and novel approaches to overcome the barrier, and a proteomic analysis of four different barriers in the CNS. The conference will conclude with a trendsetting keynote session on fluid flow and exchange in the interstitial fluid space (ISF) and the cerebrospinal fluid (CSF) space (e.g., ?glymphatics?), and how these impact drug distribution and delivery. An additional 7 sessions will address: i) the role of experimental models of brain barriers in CNS using novel bioengineering principles, ii) changes in brain barriers structure/function in disease states, iii) delivery of macromolecules to the brain, iv) understudied barriers of the CNS, v) novel methods of drug delivery across the brain barriers, vi) influence of neuroinflammation on the BBB, and, vii) CSF/ISF fluid flow and exchange in the CNS. Inclusion of clinicians in the meeting is a critical part of fostering translational discussion, with a particular goal of establishing new collaborations between basic and clinical scientists in this field. This application addresses a major public health concern; diseases of the CNS. Improving our knowledge regarding brain barrier structure and function is prerequisite to overcome these barriers to achieve appropriate diagnosis and therapy of neurological disorders ranging from brain tumors to Alzheimer's disease, diseases that are often limited to symptomatic and palliative measures. Instructing young researchers to think of innovative and novel solutions, and to bridge disciplinary interfaces in established laboratories will advance the capacity to bring new approaches to realize the untapped potential for the treatment of CNS disease.