A rodent model of mild traumatic brain injury
Perez-Polo JR., Johnson RKM., Parsley MA., Xy G-Y., Infante K., DeWitt DS., Grill RJ., Hulsebosch CE. Journal of Neurotrauma. 2013; ahead of print
Take Home Message: Among rats, inflammatory markers may be detected within 3 hours of a concussion injury and other markers of brain tissue dysfunction may be detected up to 18 days after injury.
Following a head injury there are numerous inflammatory consequences that persist over time and could contribute to prolonged recovery. Unfortunately, the pathologic changes after a concussion are still poorly understood. Therefore, the purpose of this research was to characterize the inflammatory markers as well as brain tissue’s integrity and function 3-6 hours and 18 days after an injury. The authors divided the rats into two groups: 1) rats given a mild traumatic brain injury or 2) control rats who were uninjured. The rats then recovered for 3 hours, 6 hours, or 18 days; at which point their brain tissue was evaluated. On day 11 rats performed 10 trials of beam balance assay (rat is timed while walking from center of balance beam to a platform) and foot fault assay (rat walks on wire mesh and researchers count the number of times forelimb or hindlimb falls through) to assess balance and motor coordination, respectively. Within 3 hours of injury, there were increases in several inflammatory markers within 3 different regions of the brain on the side of the injury compared to the non-injured side of the brain. These increases were even more pronounced at 6 hours post injury and an anti-inflammatory protein had become elevated. Rats exposed to the mild traumatic brain injury had impaired balance and locomotor coordination compared to control animals at day 11. There was also an increase in specific glial inflammatory proteins (promote scarring and have detrimental affects on neuron health), decrease in myelin (an electrical insulating tissue that facilitates neuron efficiency), and an increase proteins that reflect blood-brain barrier dysfunction (tightly packed layer of capillaries that protects the brain) that persisted for 18 days.
In this study, the authors found that the injured side of the brain becomes inflamed shortly after a head injury and over time these regions may develop scarring, tissue damage (myelin loss), and blood-brain barrier dysfunction. This may suggest that the brain is like other tissues in that tissue damage after an injury is a result of a combination of the initial mechanical trauma and the delayed secondary events. The inflammatory markers that were abundant following the injury are involved in several inflammatory pathways that can stimulate DNA damage, cellular machinery dysfunction, and cell death. The glial inflammatory proteins that were abundant following the injury can result in scaring and neurodegenerative outcomes, which could lead to prolonged recovery and adverse outcomes later in life. Furthermore, the blood-brain barrier dysfunction may contribute to impaired vascular function, which can leave the brain more susceptible to further downstream inflammation. This is particular interesting in light of a recent small study that found repeated head impacts, without a concussion, may be related to blood brain barrier dysfunction. In addition with blood-brain barrier impairment, myelin loss could explain adverse balance and locomotor outcomes following a brain injury. Myelin facilitates an efficient transmission of nerve signals and if it is damaged then signals can be compromised, which leads to less effective muscle movement. The authors hypothesize that if treatments could alter the secondary inflammatory cycles then perhaps we could preserve neuronal function and decrease long-term problems. In many ways, this is similar to our concerns about secondary injury after a musculoskeletal injury. The question remains, what is the most effective way to reduce the secondary injury in the brain? Do you think these inflammatory markers could also lead to concussion biomarkers for diagnosing concussions?
Written by: Jane McDevitt MS, ATC, CSCS
Reviewed by: Jeffrey Driban
Related Posts:Perez-Polo JR Ph D, Rea HC, Unabia GC, Xu G, Parsley MO, Infante SK, Dewitt D, Grill RJ Jr, & Hulsebosch C (2013). Inflammatoroy consequences mild traumatic brain injury. Journal of Neurotrauma PMID: 23360201