Drs. Helen M. Bramlett and W. Dalton Dietrich Receive $2 million NIH Research Grant
Helen M. Bramlett, Ph.D., professor of neurosurgery and psychology, and W. Dalton Dietrich, Ph.D., Scientific Director of the Miami Project to Cure Paralysis, Senior Associate Dean for Discovery Science, and professor of neurological surgery, neurology and cell biology, have been awarded a five-year $2 million grant by the National Institute of Neurological Disorders and Stroke to investigate the efficacy of combining therapeutic hypothermia and a novel pharmacological intervention to promote hippocampal neurogenesis and improve cognitive function following experimental traumatic brain injury (TBI).
The dual-PI grant will test the benefits of combining two powerful therapeutic interventions targeting different TBI-induced pathophysiological processes. Bramlett and Dietrich have a history of investigating the importance of therapeutic hypothermia and targeted temperature management in protecting the brain and spinal cord microenvironment following cerebral ischemia and trauma.
These studies, conducted with other collaborators at the University of Miami Miller School of Medicine, have helped lead to successful clinical trials targeting several neurological disorders. Most recently this research team, including Meghan Blaya, Ph.D., a post-doctoral fellow, tested the ability of the novel proneurogenic compound P7C3-A20 to enhance hippocampal neurogenesis and improve cognitive function after TBI. The overall purpose of the newly funded research is to investigate the cellular and molecular mechanisms underlying protection and enhanced neurogenesis and to demonstrate a potentially synergistic benefit of combining the treatments.
“It is hypothesized that this combination approach will target multiple secondary injury cascades, thereby providing a more permissive environment for enhanced neurogenesis, resulting in superior functional recovery,” said Dietrich. The proposal includes state-of-the-art 3D imaging approaches combined with transgenic mice to allow for hippocampal neurogenesis to be genetically ablated to test causative effects between protection, neurogenesis and functional outcomes.
“We are excited about this new work that will examine the synergistic benefits of hypothermia with P7C3-A20 treatment on both protection and repair using clinically relevant TBI models,” said Bramlett. “If positive, these findings could help promote clinical trials in patients with severe TBI.”
The new research is a dual-PI initiative, in which both Drs. Bramlett and Dietrich will be conducting the experimental protocols. Their research team includes Daniel Liebl, Ph.D., professor of neurological surgery, who will provide expertise in the proposed transgenic mouse experiments, and Pantelis Tsoulfas, M.D., associate professor of neurological surgery, who helped establish tissue-clearing strategies with 3D light fluorescence microscope imaging to critically assess regenerative processes, and who will help with the neurogenesis studies.
“Because there are limited treatments that can be provided to patients with TBI, we are excited about this new project from the basic and translational research perspectives as well as the translatable possibilities of moving this treatment strategy into the clinic,” noted Bramlett and Dietrich.