Synergy Between Exercise and a Connexin Hemichannel Blocker After SCI
Abstract
The objective of the proposed research is to understand whether physical activity is necessary for the enhanced functional recovery observed in mice with a spinal cord injury (SCI) that are treated with new orally active drug candidate, boldine. The mice have an SCI that is analogous to that experienced by patients who sustain an SCI due to trauma, such as that resulting from a motor vehicle accident, the most common cause of SCI. Boldine is thought the be the major active ingredient of a nutritional supplement made from the Boldo tree, a tree that grows in Chile. Boldo is used to prepare teas taken as an herbal remedy for a variety of disorders. Recent studies have demonstrated that one molecular effect of boldine is to plug small holes in cell membranes, through which excitatory molecules such as glutamate leak from the cell, causing toxicity to nearby nerve cells. The holes are formed by proteins called connexins, and are increased in number on non-neural cells called astrocytes following SCI. In preliminary studies, boldine administered orally to mice increased function of the back legs of mice with spinal cord contusion when evaluated using either of two different tests. These exciting findings stimulated the current proposal which, as noted above, is focused on whether physical activity is necessary for these benefits of boldine to occur. This is an important question for several reasons. First, it is well established that increasing physical activity through physical therapy can increase function after SCI. Second, there are a few studies showing that physical activity improves functional gains afforded by cell transplant therapies. Third, the current animal models of SCI allow free movement around the cage, which is thought to provide a kind of self-rehabilitation through passive movement of the limbs, which SCI patients who cannot walk do not experience. Thus, a comprehensive approach to understanding the impact of physical activity on functional outcomes, with or without treatments, is needed. The proposed research will set a paradigm for such studies of the intersection of physical activity and drug or cell transplant therapies. In addition, it will establish the role of physical activity in functional improvements resulting from treatment of mice with boldine following a clinically relevant SCI.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010328
Entities
People
- Christopher Cardozo
Organizations
- James J. Peters VA Medical Center
- United States Army