Traumatic brain injury has been in the news lately because even mild traumatic brain injury, or concussion, can increase the risk of developing neurodegenerative diseases like Parkinson’s disease (1). Many parents have understandably been worried about their children suffering from concussion as a result of playing contact sports like American football. Sports-related injuries and falls are the two most common causes of concussions in civilians (2). Blast injuries are the most common cause of traumatic brain injuries in the military.
Concussion is a widespread problem, affecting up to 40 million people around the world every year (2). Traumatic brain injuries are predicted to become the third most common cause of death by 2020 (3). However many people suffer concussion, or even more severe brain injuries and do not develop a neurodegenerative disease.
How does traumatic brain injury contribute to Parkinson’s disease?
While we know that concussion and more severe brain injuries can increase the risk of neurodegenerative diseases like Parkinson’s, it is not clear how that happens at a molecular level. Part of the problem is that is can be difficult to accurately diagnose a case of mild traumatic brain injury. There are no objective diagnostic measurements to confirm concussion (2).
Researchers around the world are searching for a rapid, accurate, objective test to diagnose mild traumatic brain injury and monitor patient recovery. If such a test were developed, clinicians could use it to assess whether athletes are fit to return to their sport after a brain injury, and when members of the military are fit to return to service.
Metabolomic biomarkers of traumatic brain injury
Researchers from the University of California, Irvine, Georgetown University and the University of Rochester have identified a panel of plasma metabolites that change after mild traumatic brain injury.
The researchers collected blood samples from 38 college athletes suffering from concussion. Students were only enrolled in the study if they had normal cognitive function in their pre-season assessment and then had an in-season concussion injury diagnosed by their team physician. Athletes were paired with age-, sex- and sport-matched controls. Blood from participating athletes was collected into EDTA tubes within 6 hours of injury, stored on ice and processed within one hour of collection.
Scientists at the Metabolomics Shared Resource at Georgetown University performed metabolomic analysis on plasma from the participating athletes. The scientists first used liquid chromatography-mass spectrometry (LC-MS) to discover any metabolites altered in plasma after brain injury and then used tandem mass spectrometry (MS-MS) to confirm these changes. They found a panel of 6 metabolites that changed in plasma samples within 6 hours of a mild traumatic brain injury (2). These metabolites remained significantly different from control samples for up to 7 days post-injury.
The researchers confirmed this panel of 6 metabolites on a separate independent cohort of 31 traumatic brain injury patients.
Glutamic acid might link traumatic brain injury and Parkinson’s disease
In a second separate study, authors looked for metabolomic biomarkers in subacute traumatic brain injury and in patients with Parkinson’s disease. This study enrolled 75 active duty sailors and marines who had suffered a traumatic brain injury in the past 3-6 months and 20 controls. They also enrolled 20 Parkinson’s disease patients, 20 Parkinson’s disease dementia patients and 20 controls (4). The brain injury study population was skewed because 71 of the 75 brain injury patients were male.
The results of this study showed that glutamic acid remains significantly increased in the plasma of patients 3-6 months after traumatic brain injury. In contrast, glutamic acid is significantly decreased in patients with Parkinson’s disease compared with controls. These data support previous studies showing that the ratio of glutamic acid to glutamate changes in children and adults after traumatic brain injury. Glutamic acid is an excitatory neurotransmitter that regulates brain cell function. These results suggest that glutamate might be part of the molecular mechanisms by which traumatic brain injury contributes to Parkinson’s disease. However, it still isn’t clear why this happens in some patients and not in others.
These studies show that circulating metabolites in plasma might be useful biomarkers of traumatic brain injury. If researchers can find a reliable panel of plasma biomarkers, this test could be used to objectively diagnose brain trauma and to monitor patient recovery. However, both these studies had small populations. Furthermore, the brain injury population in the second study was 95% male. Therefore, the results of these studies need to be confirmed in larger populations to verify the reliability of the metabolomic biomarkers.
- Gardner et al. Mild TBI and risk of Parkinson disease: A Chronic Effects of Neurotrauma Consortium Study. 2018.
- Fiandaca et al. Plasma metabolomic biomarkers accurately classify acute mild traumatic brain injury from controls. PLoS One. 2018.
- Meaney et al. The mechanics of traumatic brain injury: a review of what we know and what we need to know for reducing societal burden. J Biomech Eng. 2014
- Fiandaca et al. Potential Metabolomic Linkage in Blood between Parkinson’s Disease and Traumatic Brain Injury. Metabolites. 2018