Treatment Tested to Break TBI-Alzheimer’s Link

by U.S. Medicine

August 9, 2015

FRANKFORT, KY — The cascade of events following mild traumatic brain injury (mTBI) appears to increase the risk for developing a progressive degenerative brain disease, and researchers now are testing a treatment that might interrupt the process linking the two events.

For the animal study, the study published recently in the Journal of Neuroscience employed mice that have been genetically altered to make amyloid beta, which is a key to Alzheimer’s disease. The researchers from the University of Kentucky’s Sanders-Brown Center on Aging also developed a surgical procedure to mimic the most common form of TBI.1

“By defining the cascade of events that occurs after a mild brain injury, we ultimately hope to discover ways to disrupt that process,” said co-author Adam Bachstetter, PhD. “Our goal is to uncover the biology that underlies the link between head injury and dementia, and in our latest research, we think we have found evidence that an altered inflammatory response from cells in the brain called glia may be at least part of the link.”

“We wanted to know if we could accelerate the onset of memory problems in these mice, similar to what is believed to occur in humans,” added co-author Scott Webster, PhD. “It gave us a way to ask the important mechanistic questions that might one day lead to a better treatment for head injury patients.”

Bachstetter and Webster experimented with a small molecule drug known as MW151, which blocks overproduction of the molecules that cause inflammation in the brain following TBI. It was given to the mice starting a week after TBI, and after three weeks of treatment, the rodents that received MW151 no longer showed learning and memory problems. The others with a TBI continued to demonstrate profound learning and memory problems.

“MW151 was able to rescue the memory impairments in mice even when treatment was started a week after the injury,” said Webster. “The potential implications are compounded when you factor in that many people who suffer a mild brain injury don’t seek treatment right away.”

Study authors said that could be especially significant for war-injured TBI victims.

“As the signature injury of the Iraq and Afghanistan wars, and with approximately 1.5 million people in the United States each year seeking medical treatment for a traumatic brain injury,” explained co-author Linda J. Van Eldik, “the impact of earlier onset of dementia in such a large number of people is simply unthinkable.”

1Webster SJ, Van Eldik LJ, Watterson DN, Bachstetter AD. Closed Head Injury in an Age-Related Alzheimer Mouse Model Leads to an Altered Neuroinflammatory Response and Persistent Cognitive Impairment. Journal of Neuroscience, April 2015 DOI: 10.1523/JNEUROSCI.0291-15.2015.


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