A blood clot forming in the carotid artery. Credit: copyright American Heart Association
P7C3 compound protects mature and newborn neurons in rats, and also improves physical and cognitive outcomes, following stroke. Researchers from the University of Iowa Carver College of Medicine and University of Miami Miller School of Medicine have shown a neuroprotective compound tested in rats provides two-pronged protection for brain cells during stroke and improves physical and cognitive outcomes in the treated animals.
Every year, nearly 800,000 Americans have a stroke and almost 130,000 die. When a stroke interrupts the brain’s blood supply, neurons die. In addition, reestablishing blood flow, ie reperfusion, also leads to processes that cause cell death. A part of the brain’s natural response to stroke injury is to increase production of new brain cells in two specific regions (subgranular zone of the hippocampal dentate gyrus and the subventricular zone of the lateral ventricles), which normally make a smaller number of new brain cells every day. Unfortunately, the most newborn cells die within 1 – 2 weeks, limiting the benefit of this repair process. Minimizing the loss of brain cells is a primary goal for new stroke therapies.
“If we could prevent the mature brain cells from dying that would be beneficial,” says Prof, Andrew Pieper, MD, PhD. “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.” Using rats, Pieper and his colleagues tested P7C3-A20. Blood flow to the rats’ brains was interrupted for 90 minutes and then the blockage was cleared allowing reperfusion. One group of rats was given the P7C3-A20 compound twice daily for 7 days following the stroke. P7C3-A20 has previously been shown to prevent brain cell death in other animal models of neurologic injury, including Parkinson’s disease, amyotrophic lateral sclerosis (ALS), stress-associated depression, and traumatic brain injury (TBI).
In terms of the brain itself, the P7C3-A20 compound reduced atrophy and increased survival of newborn neurons 6 weeks after stroke. In addition to the improved survival of both mature and newborn neurons, rats that received P7C3-A20 for 7 days after stroke also had better physical and cognitive outcomes than untreated rats. Treated rats had improved balance and coordination 1 week after stroke, and improved learning and memory 1 month after stroke.
“There is no previous demonstration of a pharmacologic agent that both protects mature neurons from dying and also boosts the net magnitude of neurogenesis,” Pieper says. “Our compound is beneficial in this animal model of stroke, and we’re hopeful that it might eventually benefit patients.”
The neuronal protection provided by the P7C3-A20 compound was also associated with a boost in the levels of nicotinamide adenine dinucleotide (NAD) in the rats’ brains. NAD is emerging as an important player in neuronal health and survival. Levels of this substance are depleted during stroke, and it has been proposed that increasing NAD levels may be a therapeutic target for treating stroke. In this study, P7C3-A20 treatment restored NAD to normal levels in the rats’ cortex after a stroke.
The sustained physical and cognitive improvement seen in the rats up to one month after the stroke suggests that the P7C3-A20 compound provides a long-term benefit. In recent years, advances in treatments that break up or remove stroke-causing blood clots have reduced the death rate for stroke and are improving outcomes for patients. The researchers hope that a treatment based on P7C3-A20 used in addition to the clot-clearing therapies might further improve outcomes by protecting brain cells during the traumatic ischemia/reperfusion period. http://www.sciencedirect.com/science/article/pii/S0014488617300055 https://medicalxpress.com/news/2017-03-brain-cells.html
Recent Comments