Rotational Force-Induced Brain Injury Model

This innovation is a new instrument, model, and treatment for repetitive rotational head trauma in rodents that demonstrates the acute and prolonged pathological, behavioral, and electrophysiological effects of rotational traumatic brain injury (rTBI). Aberrant Cyclin-dependent kinase 5 (Cdk5) activity is a principal mediator of rTBI. Cdk5-enriched phosphoproteomics is used to uncover potential downstream mediators of rTBI and show that pharmacological inhibition of Cdk5 reduces both cognitive and pathological consequences of injuries. 

Background: 
Millions of traumatic brain injuries (TBIs) occur annually. TBIs can result from falls, traffic accidents, sports-related injuries, explosions, and other rotational accelerations/decelerations of the brain. During these events, the brain endures a multitude of primary injuries, including compression of brain tissue, damaged vasculature, and diffuse axonal injury. These deleterious effects can contribute to secondary brain ischemia, cellular death, and neuroinflammation that progress for weeks, months, or a lifetime after injury. While the linear effects of TBIs have been extensively modeled, less is known about how rotational injuries mediate neuronal damage following injury. This novel instrument, model, and treatment can contribute meaningfully to revealing the mechanisms of rTBI and how they may be effectively treated.

Applications:

• Research: the instrument and model can be used in preclinical research to study the acute and long-term effects of rotational traumatic brain injuries on neuronal function, cognitive outcomes, and electrophysiological changes
• Treatment development: the treatment using pharmacological inhibition of Cdk5 could be developed into a therapeutic option for individuals with rTBI, pending further research and clinical trials
• Diagnostics: the production of models for rTBIs and regulation of Cdk5 can improve a patient’s diagnosis and outcome

Advantages: 

• Increased understanding: the instrument and model can help researchers and clinicians better understand the mechanisms of rTBI and identify potential targets for intervention
• Improved outcomes: the treatment using pharmacological inhibition of Cdk5 could potentially improve cognitive outcomes and reduce pathological consequences of rTBI, thereby improving the overall quality of life for individuals who suffer from this type of injury