New data spotlights key molecular mechanisms that enable human neural stem cells to assist in recovery from traumatic axonal injury, according to researchers at the University of Texas Medical Branch (UTMB), headquartered in Galveston, Texas. UTMB professor Ping Wu, MD, PhD, led the study. Wu explains that, “In this study, we found that our stem cell transplantation both prevents further axonal injury and promotes axonal re-growth, through a number of previously unknown molecular mechanisms.”
Researchers report that prior studies suggested neural stem cells secrete a substance known as glial derived neurotrophic factor (GDNF), which appeared to assist injured rat brains in recovery from injury. Using this previous data, researchers reportedly focused their efforts on spotlighting the mechanics behind the process that yields the beneficial effects of GDNF and neural stem cell transplantation. According to the research team, proteomic techniques were used to compare injured rat brains into which neural stem cells had been transplanted to injured rat brains that had not received the transplant.
Wu says that the team identified 400 proteins that respond differently after injury and after grafting with neural stem cells. After grouping the proteins using a sophisticated internet database, “we found that a group of cytoskeleton proteins was being changed, and in particular one called alpha-smooth muscle actin…” Wu explains.
The study’s focus reportedly shifted to traumatic axonal injury, using a rat model. Study results suggested that when axons and dendrites suffered damage from trauma, implanted neural stem cells reduced harm and lowered levels of alpha-smooth muscle actin inside neurons that were elevated following trauma. To spotlight GDNF’s role in reducing traumatic axonal injury, researchers say the goal of their “rapid stretch injury model” was to simulate the sudden compression and stretching forces exerted on brain cells by a blow to the head. To accomplish this, the team reportedly placed human neurons on a flexible membrane, which was then distended with a calibrated puff of gas. The model’s initial findings mirrored those exhibited in the rat model, researchers say, suggesting that alpha-smooth muscle actin levels elevated by simulated injury were significantly reduced by the implanted neural stem cells and that GDNF protected axons.
Researchers add that they also identified evidence that links alpha-smooth muscle actin with RhoA, a small protein hat blocks axonal growth after injury. “…We know much more about how GDNF protects axons and dendrites from further injury and promotes their re-growth after trauma,” Wu says, adding, “This kind of detailed study is essential to developing safe and effective therapies for traumatic brain injury.”