Newly Published Collaboration Shows Promise in Saving Brain Cells Following Stroke

W. Dalton Dietrich, Ph.D., Scientific Director, The Miami Project, Kinetic Concepts Distinguished Chair in Neurosurgery, Senior Associate Dean for Discovery Science, and Professor, Neurological Surgery, Neurology and Cell Biology, and colleagues, recently published The Neuroprotective Compound P7C3-A20 Promotes Neurogenesis and Improves Cognitive Function after Ischemic Stroke in the journal Experimental Neurology.

Stroke is the leading worldwide cause of adult long-term disability. Over the last decade tremendous advances in acute stroke therapy have been made to reduce mortality rate. However, currently only one FDA approved drug, tissue plasminogen activator, is used in the clinic to improve neurological function in acute stroke patients. Unfortunately, very few patients receive treatment. Additional research is required to develop and test novel neuroprotective therapies that can help improve outcomes.

The current experimental study that was conducted by Zachary B. Loris, a 4th year doctoral Neuroscience candidate, and colleagues who evaluated the effects of a novel neuroprotective compound P7C3-A20 after stroke. P7C3-A20 has been reported in many pre-clinical studies to protect mature neurons as well as enhance the formation of new immature neurons (i.e., neurogenesis). In this study, animals that had been given an experimental stroke were treated with P7C3-A20 to determine the long-term benefits on behavior and tissue damage. The authors hypothesized that early treatment after experimental stroke would protect adult neurons from irreversible damage, while also promoting the formation of new neurons that would result in better functional outcomes.

“Currently there are limited treatments for acute stroke that make a real difference in patient’s lives. There is an urgent need to identify, test and translate new therapies to the clinic,” explains Dr. Dietrich. “The ability to both protect and repair the injured nervous system has major implications on how we think about improving outcomes in millions of people each year with acute neurological injuries.”

The manuscript reports that P7C3-A20 treatment significantly improved behavioral outcomes including sensorimotor and memory function compared to non-treated animals. Treated animals also had an increased numbers of newly formed adult neurons in two specific brain regions and reductions in lesion size. Together these studies provide the first data showing that the novel proneurogenic compound P7C3-A20 is beneficial in experimental stroke and leads to improvements and long-term function. Dr. Dietrich emphasized that novel compounds like P7C3-A20, that are currently targeted for drug development, may potentially be translated into the clinic to protect against secondary injury mechanisms after brain injury, as well as enhance reparative strategies leading to clinically relevant behavioral recovery.

“If we could prevent the mature brain cells from dying that would be beneficial,” says Dr. Andrew Pieper a co-author and University of Iowa Professor. “But if we could also support or enhance this surge in neurogenesis (birth of new neurons), we might be able to further foster recovery, especially in terms of cognitive function, which is critically dependent on the hippocampus.”

The research was supported by funding from the American Heart Association, The Miami Project to Cure Paralysis, the Mary Alice Smith Fund for Neuropsychiatry Research, the Titan Neurologic Research fund, and the University of Iowa and the Department of Veterans Affairs.