Research Effectively Models Rotational TBI and Uncovers Potential Neuroprotective Therapies

Every year, millions of people suffer from Traumatic Brain Injury (TBI) around the world. Caused by an external force – like a blow to the head that disrupts normal brain function – TBIs can often lead to a wide range of symptoms after an injury. Many patients have reported headaches, memory loss, difficulty concentrating and paying attention, mood swings, and even trouble sleeping.

“These symptoms can be incredibly disruptive to a person’s day-to-day life, leading to reduced quality of life, difficulty at work and strained relationships with loved ones,” said James A. Bibb, Ph.D.chair of the Department of Translational Neuroscience at the University of Arizona College of Medicine – Phoenix.

Despite the prevalence of head trauma, the treatment options available are limited; and, currently, most treatments focus on managing the symptoms rather than the underlying injury. Dr. Bibb attributes these approaches to a lack of understanding of the mechanisms behind TBI and how they affect the brain.

Most head injuries are the result of falls, traffic accidents, or sports-related head injuries – where the brain is damaged by the rapid acceleration/deceleration of the brain within the skull. Recreating these experiments in a controlled laboratory environment is very difficult. “Very few preclinical models of TBI recapitulate these negative rotational lesions. This made it difficult to study the effects of TBI and test potential treatments in a controlled environment,” Dr. Bibb said.

Yet a recent study by Umfress et. Al- Posted in Scientific reports and conducted in Dr. Bibb’s lab – highlights the development of a new model of TBI induced by rotational acceleration.

Using complex mechanical engineering and high-speed telemetry, Dr. Bibb and his colleagues were able to design and characterize this new model, which unveiled numerous neuropathological consequences of injury.

The researchers used in vivo translational imaging of resident immune cells to demonstrate diffuse neuroinflammation after rotational head trauma. In partnership with cell signaling technology, they also used proteomic strategies to identify cyclin-dependent kinase 5 (Cdk5) as the primary perpetrator of TBI-induced memory impairment.

They paired it with a new Cdk5 inhibitor – also discovered by Dr. Bibb’s lab – to demonstrate neuroprotection against these memory impairments and other neuropathological changes. Their progress provides fundamental steps toward modeling clinically relevant forms of TBI, identifying biochemical alterations in the brain, and developing novel neuroprotective therapies.

“The chronic effects of TBI include an increased risk of developing neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease. And repetitive TBI can lead to degenerative conditions such as chronic traumatic encephalopathy (CTE) – a condition commonly seen in professional soccer players and other contact sports athletes,” Dr. Bibb explained. It is vital that researchers develop more effective therapies.

This multi-institutional study included collaborative contributions from the University of Texas at Dallas Erik Jonsson School of Engineering and Computer Science, University of Texas Southwestern, University of Alabama at Birmingham, Cell Signaling Technology and from the UArizona College of Medicine – Phoenix Department of Translational Neurosciences.