New Brain-Injury Research Starts Small -- With Fruit Flies

Tue, 2013-10-15 12:33 -- llancaster
Oct 15 2013 - 12:30pm
By: Chris Gorski, Senior Editor, Inside Science
Fruitflies exhibit human-like symptoms of traumatic brain injury following mechanical impact. | Image courtesy of Grace Boekhoff-Falk and David Wassarman, University of Wisconsin-Madison.

Traumatic brain injuries represent one of the biggest ongoing stories in sports. These injuries can happen off the field, as a result of accidents or trauma, or due to a collision during a game -- football gets the most press coverage for them, but they can occur in many sports. When the head stops moving suddenly, the brain sloshes around inside the skull, and that sudden movement can cause an injury, with a severity, duration, and long-term effect that can vary greatly.

There's a lot of research going on in the area, and it's the subject of PBS documentariesbooks, articles, and lawsuits. The science of brain injuries is still relatively young, and the exact cause-and-effect relationships somewhat uncertain.

A new study published this week joins the growing body of research on the subject and approaches these injuries in a new way. Scientists have developed a way to study brain injuries in fruit flies, specifically the species Drosophila melanogaster. Scientists have long used fruit flies to study genetics. The well-established techniques and tools to analyze fruit flies and their genetics make the insects attractive for the study of brain injuries. In fact, scientists have already begun examining the relationship between genetics and brain injuries.

As I wrote in a previous post:

"In David Epstein's recent book, 'The Sports Gene,' he describes research that demonstrates a genetic element to concussion risk. He explains that a gene called ApoE seems to be related to brain injury and also Alzheimer's disease risk. People carry two copies, inherited from their father and mother, and if one of them is a variety [or allele] known as ApoE4, the risk of Alzheimer's is increased three-fold. If both copies are ApoE4, the risk is eight times higher. Epstein wrote that one researcher told him the risk of dementia for people with 'a single ApoE4 copy is roughly similar to the risk from playing in the NFL, and that the two together are even more dangerous.'"

Working with a team of researchers, David A. Wassarman, a professor of cell & regenerative biology at the University of Wisconsin-Madison, developed a way to investigate the consequences of brain injuries in fruit flies. They described the research in an article for the latest issue of the journal Proceedings of the National Academies of Sciences. It may help lead to an increased understanding of the relationships between head trauma and brain injury.

Wassarman answered the following questions in an email exchange.

Inside Science: Why make a Drosophila model of brain injuries? Why work with an insect instead of something like a small mammal?

Wassarman: The major advantages of flies over small animals is that we can rapidly and inexpensively study many animals under many conditions. For example, in our paper, we studied hundreds of thousands of flies and we were able to determine the effect of different conditions, i.e., sex, age at the time of injury, and genetic background, on TBI [traumatic brain injury] outcomes.  

IS: What sorts of insights do you foresee that your team or others might be able to develop from your model? 

Wassarman: Our major goal is to understand the cellular and molecular events that cause TBI outcomes. Right now we are using genetic approaches to identify genes that make wild-type flies resistant or susceptible to TBI outcomes. This understanding will lead to approaches to diagnose and treat TBI patients.

IS: Please describe the how the model works.  

Wassarman: Closed-head TBI in humans is caused by mechanical damage to the brain that results from rapid acceleration and deceleration of the brain. To mimic this in flies, we built a Hit-Impact Trauma (HIT) device. The device consists of a large metal spring that is attached at one end to a board. Flies in a plastic container are attached to the free end of the spring. We inflict injury by bending and releasing the spring; the vial hits a plastic pad and the flies impact the side of the container. Important features of this approach are that we can inflict injury to many flies at the same time and we can reproducibly inflict the same injury.    

IS: It seems like such a basic place to start, studying Drosophila. Does the need for such a model imply that the state of current knowledge about brain injuries and concussions is in its infancy?  

Wassarman: I think that TBI research is in its infancy. Most of what we know about TBI is correlative. For example, it is known from examining the brains of athletes in contact sports that injuries to the brain correlate with a form of neurodegeneration called Chronic Traumatic Encephalopathy (CTE), which shares features with Alzheimer's disease. But, it is not known whether injuries to the brain are the sole cause of CTE, it is not known how to predict whether and when an individual will get CTE from a brain injury, and it is not known how to prevent or delay CTE.   

IS: Your research paper mentions the well-developed genetic techniques used to study Drosophila as one of the advantages of using them in this field of research. Down the line, do you think you might be able to learn more about the ApoE4 allele, or others that might suggest genetic predisposition or vulnerability to brain injuries?  

Wassarman: Yes, this is one of our major goals. We have used a genetic approach to identify a number of genes that correlate with either predisposition or vulnerability to one of the outcomes of brain injury. Interestingly, 3/4 of these fly genes are also found in humans and some of these have already been implicated in neurological disorders. We are collaborating with a clinical researcher to determine if these genes are predictors of TBI outcomes in humans.

Previous coverage of traumatic brain injuries and concussions on Inside Science is available at the following links:

Measuring Forces, Impacts on Youth Football Helmets

Football, Explosions Rattle Brain in Similar Ways 

Concussions: Lots Of Ink, More To Come

Protecting Against Concussions in Football and Beyond

Protecting Against Concussions: Helmet Research


 
Chris Gorski is a Senior Editor for Inside Science and tweets at @c_gorski.
 
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