The Transport of Neurotoxicant Antidotes Across the Blood-Brain Barrier
Abstract
The blood-brain barrier comprises 600 km of capillaries that supply nutrients and other essential molecules to the brain while maintaining tight control of the microenvironment in which neurons and other brain cells function. Since the blood-brain barrier is designed to regulate entry of non-essential molecules into the brain, the delivery of drugs to treat diseases of the brain is extremely challenging. Elucidating the mechanisms of transport of neurotoxicant antidotes and other small molecules across the blood-brain barrier is key to develop new delivery strategies and methods for screening next-generation antidotes. Neurotoxicant antidotes are molecules that can reverse the effects of exposure to chemical substances that disrupt the nervous system resulting in neurological dysfunction or cognitive impairment. The objective of this multidisciplinary project is to provide new insight into the transport of neurotoxicant antidotes across the blood-brain barrier. Combining a novel artificial microvessel assay, in vivo imaging using two-photon microscopy, and molecular dynamics simulations, we will elucidate the influence of nerve agents on the structure and function of the blood-brain barrier, and assess the mechanism of transport of oximes and other related molecules across the blood-brain barrier. Together, the output from this project will enable improved delivery of neurotoxicant antidotes, and provide new tools to enable other researchers to advance risk assessment and the development of medical countermeasures.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- May 26, 2016
- Source ID
- HDTRA11510046
Entities
People
- Peter C. Searson
Organizations
- Defense Threat Reduction Agency
- Johns Hopkins University