Porcine Model of Focal Traumatic Brain Injury

Summary

Traumatic brain injury (TBI) is one of the leading causes of death and long-term disability among persons in the United States with toddler age children being one of the largest populations affected. Despite the number of people who are affected by TBI, there remains to be no effective treatment. One of the difficulties in developing effective treatments for TBI has been the poor translatability of therapies from the widely-used rodent models to human patients. In this study we develop a novel piglet focal traumatic brain injury model comparable to toddler age children. The developed piglet model displays brain lesioning, loss of neurons and motor function deficits similar to human patients. These data suggest that the piglet model is comparable to human patients and will likely be more predictive of human out comes for drug, device and other therapeutic treatments.

Situation

A traumatic brain injury (TBI) occurs when an external force causes damage to the brain. Each year, on average, TBIs are associated with an estimated 1.1 million emergency department visits, 235,000 hospitalizations, and 50,000 deaths in the United States. Persons of all ages, ethnicities, and incomes can be affected by a TBI. Babies, toddlers, and young children make up the largest percentage of individuals that experience a concussive TBI- largely due to falls. Due to the large number of persons effected by TBI, significant efforts have been made to produce effective treatments, yet there is still no FDA approved treatment for TBI.

Response

One of the major limitations of treatment development has been the lack of treatments developed in rodents to be effective in human clinical trials- resulting in the loss of significant time and resources. This suggests that an animal more similar to humans may lead to better predictability of a human outcome in response to a therapeutic. To address this need, our team tested the ability of blunt force trauma to lead to human like changes in the brain at a cellular, tissue and functional level in a novel piglet TBI model. At the cellular level, injury resulted in increased levels of reactive astrocytes and a decreased number of neurons. At the tissue level, injury resulted in a significant brain lesioning. Motor function analysis showed that animals increased time in a 3 limb support phase and had an increased stride duration suggesting decreased stability characteristic of motor function problems due to TBI. These data suggest that the piglet model is comparable to human patients and will likely be more predictive of human out comes for drug, device and other therapeutic treatments.

Impact

The development of a robust and more predictive piglet TBI model will enable more rapid and cost effective development of TBI therapies. This model has broad reaching implications for the study of the pathophysiology of other neurological diseases and injuries.

State Issue

Other Issue

Details

• Year: 2016
• Geographic Scope: International
• County: Clarke
• Program Areas:
  • Agriculture & Natural Resources