Despite huge efforts from the U.S. government and private sector, new research published in the Journal of Neuroscience suggests the Holy Grail in brain injury diagnosis may not be possible after all.
The animal study says complications involving the brain’s waste removal system – which has been only recently discovered – could potentially prevent researchers from ever identifying biomarkers which can be effectively used to detect traumatic brain injury.
Due to the brain’s waste removal system, proteins triggered by brain injuries are prevented from reaching the levels needed in the blood stream for precise diagnosis.
These findings come after several years of hunting for a blood biomarker for TBI which has been facilitated by tens of millions of dollars from the American government and countless investments from the private sector.
“These findings show that a blood-based biomarker for TBI is unlikely to be effective for routine clinical use,” said Maiken Nedergaard, M.D., D.M.Sc., co-director of the University of Rochester Medical Center (URMC) Center for Translational Neuromedicine and lead author of the study. “Both the injury itself and the clinical approach to TBI can impair the ability of the brain to remove waste, resulting in variable and – for the purpose of detection and diagnosis – unreliable protein levels in the blood.”
While new tools are being quickly developed to aid in the diagnosis of traumatic brain injury, a large amount of the testing and evaluation rely solely from consulting with patients and gaining subjective information. Health professionals have hoped to find a biomarker which could be used to provide quick, objective diagnosis, but these findings indicate those hopes may be in vain.
Researchers have only recently started to understand how the brain manages waste. The unique waste removal system within the brain was only discovered in 2012, and was titled the glymphatic system by scientists at the University of Rochester. This system acts as a plumbing network along the brain’s blood vessels and pumps cerebral spinal through brain tissue in order to flush out waste. This waste is taken to the lymph nodes where it eventually is sent to the general blood circulation system and, finally, the liver.
During a brain injury, specific proteins are released from the brain, which has fueled the hope of measuring these proteins to provide a brain injury diagnosis.
The scientists from Rochester performed several tests on mice who had been given traumatic brain injuries, including testing the animal’s blood for three proteins commonly thought to be strong candidates for a blood-based biomarker for TBI.
The team noticed the glymphatic system was surprisingly delicate, and can be easily disrupted by brain injuries. Due to this disruption, the brain is unable to properly remove these proteins from the brain.
On top of this, the recent study also shows that treatment for brain injuries also have the potential to impair the brain’s ability to remove waste. Similar to a water pump, the glymphatic system needs pressure to properly function, but excess pressure is a common issue in moderate to severe TBI. The most common treatments for this issue involve working to relieve swelling and pressure after an injury, but this has the side effect of “depressurizing” the glymphatic system.
“This study shows that even small changes can modulate the brain’s ability to clear waste,” said Benjamin Plog, an M.D./Ph.D. student in Nedergaard’s lab and a co-author of the study. “Consequently, we need to recalibrate our efforts and begin to think about measuring brain damage in a manner that takes into account the level of impairment to the glymphatic system.”