A natural form of vitamin E called alpha-tocotrienol can protect brain cells after a stroke, by producing the MRP1 protein. The multidrug resistance-associated protein 1 works by sweeping away the toxins from the nerve cells.
The MRP1 route is one of three mechanisms identified so far, by which this form of vitamin E may be used to protect brain cells after a stroke - that is, this natural substance might be more potent than drugs targeting single mechanisms for preventing stroke damage.
Vitamin E occurs naturally in eight different forms, and the most commonly known type is called tocopherols. But for their part, the Ohio State University researchers have been focusing on the tocotrienol form (TCT). They have previously reported that in this form, vitamin E protects the brain after a stroke by blocking an enzyme from releasing toxic fatty acids and inhibiting activity of a gene that can lead to neuron death.
TCT is not abundant in the American diet but is available as a nutritional supplement. It is a common component of a typical Southeast Asian diet.
In this new study, the researchers first found MRP1 protein clears away a compound that can cause toxicity and cell death when it builds up in neurons as a result of the trauma of blocked blood flow associated with a stroke.
They then determined that TCT taken orally influences production of this protein by elevating the activity of genes that make MRP1. This appears to occur at the microRNA level; a microRNA is a small segment of RNA that influences a gene's protein-building function.
This is one of the first studies to provide evidence that a safe nutrient - a vitamin - can alter microRNA biology to produce a favorable disease outcome," said Chandan Sen, professor and vice chair for research in Ohio State's Department of Surgery and senior author of the study. "Here, a natural nutritional product is simultaneously acting on multiple targets to help prevent stroke-induced brain damage. That is a gifted molecule."
The research appears online and is scheduled for later print publication in the journal Stroke.
Over the past decade, Sen has led numerous studies on how the TCT form of vitamin E protects the brain against stroke damage in animal and cell models, and intends to eventually pursue tests of its potential to both prevent and treat strokes in humans. Approximately 795,000 Americans suffer new or recurrent strokes each year, and stroke is the third-leading cause of death in the United States, according to the American Stroke Association.
These latest research findings in mice follow a recent Food and Drug Administration certification of TCT as "Generally Recognized as Safe." The scientists conclude in the paper that even before clinical trials can take place, "TCT may be considered as a preventive nutritional countermeasure for people at high risk for stroke."
The researchers compared mice that were treated with TCT supplements or corn oil as a control for 13 weeks before a stroke was induced. The amount of damaged brain tissue was smaller in the mice that received TCT supplementation than in the mice receiving corn oil. In addition, TCT supplementation was associated with a lower level of the candidate microRNA in the damaged brain tissue, as well as an increase in the abundance of MRP1 cells at the stroke site.
"Essentially what we are showing with mechanistic explanation is that tocotrienol protects neural cells. It is anti-neurodegenerative," Sen said. "This form of vitamin E helped us identify three major checkpoints in stroke-related neurodegeneration that were not known before we began testing tocotrienols against neurodegeneration."