$1.36 million grant “Polarized initiation of varicosity formation in central neuron mechanosensation” supported by National Institute of Neurological Disorders and Stroke

An Ohio State researcher has received a nearly $1.36 million federal grant to help determine why the mechanical impact of mild traumatic brain injuries (TBIs) varies among individuals who experience them.

Chen Gu, PhD, associate professor in the College of Medicine, Department of Biological Chemistry and Pharmacology, received the grant from the National Institute of Neurological Disorders and Stroke, a division of the National Institutes of Health, for a study titled “Polarized Initiation of Varicosity Formation in Central Neuron Mechanosensation.”
 
Individuals with a mild TBI, which occurs when the brain or head sustains minor injury, trauma or concussion, typically lose consciousness or become disoriented for a period lasting under 30 minutes. The mechanical effects of mild TBIs can vary, depending on the individual, and Gu—whose research focuses on fundamental sensation mechanisms of the brain’s nerve cells—hopes to learn why.

In the project abstract, he notes that the study findings may contribute to the development of new strategies for diagnosing and treating mild traumatic brain and nerve injuries, as well as chronic disorders such as glaucoma, Alzheimer's and Parkinson's diseases, and multiple sclerosis.

 

Gu hypothesizes that the mechanical stress of brain injuries affects parts of nerve cells with a strong bias. Nerve cells, or neurons, are the key functional unit in the brain and possess a fascinating polarized structure, he says, adding that his team’s pilot studies have identified a potential rapid mechanism at the primary stage of brain injury, like during a concussion, that can be regulated by the products of several DNA fragments embedded in the genome. Gu and his team are the first to propose and test this hypothesis.

 

To investigate, Gu and his team are utilizing various methods, including collaborations with a biomedical engineering team at Ohio State to mimic the micromechanical stress that a brain may experience at the time of injury, and with a team at Washington University to establish in vivo mouse models of repeated, close-skull impact. At the genetic level, Gu says, knockout mice will allow for the deletion of certain proteins, such as ion channels and microtubule binding proteins, to determine the reversibility of injury compared to the wild type.

 

Previous research alludes to why some injuries are permanent and why others can be repaired. Shown by in vivo and in vitro models, evidence points to younger kids and their susceptibility to mechanical stress on the brain. Generally, they are more susceptible than adults; however, their neurons may have the ability to recover at a faster rate than adult neurons. This means that kids are more susceptible to head injury, but are able to recover better if the injury happens below a specific threshold.

 

One of Gu’s goals is to determine the threshold limit that defines brain injury.

 

“At the end of the study, we will hopefully understand the differential point that defines harmless vs. harmful impact,” he says. “The important question to answer in the field of brain injury is, ‘what is the limit?’”

 

Gu and his team hope to learn why some forms of impact on the brain are accumulative and others are not. Extremity of impact and its relative effects are a core foundation of neuroscience that is yet to be understood, he says.

 

Mild TBI is an important issue in sports, but also in daily life. Gu’s research has the potential to benefit all people of all ages. More importantly, he hopes that this mild TBI research will help identify potential strategies to prevent and reduce the risk of concussive injury.

 

“We can send a man to the moon, but we still don’t know enough about our own brain,” Gu notes. “Our data are becoming more and more interesting, so we are apparently on the right path to important discovery.”