Think aBout It 2025- Biomarkers and Brain Injuries

Introduction 

We know that about 2.8 million Americans sustain brain injuries each year, and an estimated 5.3 million Americans are living with disabilities related to traumatic brain injury. That means, for many, the effects of TBIs are long lasting. With brain research as one of the most complex and last frontiers in medical research, we are excited to continue Plus One Foundation’s education campaign on neurological conditions and TBIs and associated research. 

Each quarter we feature educational information and outreach on a neurological topic. Education is at the heart of what we do; our Think aBout It campaign aims to dig deeper into all aspects of TBIs and neurological conditions. This segment is on the medical developments with biomarkers and TBIs. 

Biomarkers 

What is a biomarker? 

Molecular biological markers, or protein biomarkers, are natural products that can be traced to a biological origin. Biomarkers are soluble or suspended molecules (proteins, DNA, microRNA) in circulation or found in secretions. They can be powerful tools used to trace diseases, drugs and environmental contaminants in the human body. There are also imaging biomarkers and genetic biomarkers: however, the most effective biomarkers are organic compounds with specific biological sources.

Why do biomarkers matter with TBIs?

The complexities of TBI pathology, together with the large variation of injury patterns make diagnosis and treatment challenging.  Advancements in biomarker research offer promise in improving the diagnosis, treatment, and ultimately, the optimal outcomes for individuals affected by TBIs because they can enhance diagnosis and tailor treatments. Biomarkers can show normal healthy tissue (brain matter, or any other cell type in the body), or the extent and type of damage that has occurred due to injury or illness. By studying these markers, they can predict the response to therapy (effect modifiers), predict outcomes (surrogate endpoints), risk assessment, screening, diagnosis, pharmacogenetics, and patient monitoring during and after treatment. Similar biomarkers are currently used to treat multiple types of cancers and genetically based diseases. In this segment we will cover the biomarkers that provide better measurable indicators of the biological progression of brain injuries. 

What are the biomarkers in the TBI area? 

Structural proteins: 

We know that proteins are released into the bloodstream following damage to brain cells. To date, the biomarkers discovered after neuronal cell body injury include Ubiquitin Carboxy-terminal Hydrolase L1 (UCH-L1), Neuron Specific Enolase (NSE), astroglial injury (GFAP, S100B), neuronal cell death (αII-spectrin breakdown products), axonal injury (NF proteins), white matter injury (MBP), post-injury neurodegeneration (total Tau and phospho-Tau), post- injury autoimmune response (brain antigen-targeting autoantibodies), and other emerging non- protein biomarkers have been discovered.

UCH-L1 and NSE are currently used to diagnose post-TBI diseases, such as chronic traumatic encephalopathy and Alzheimer’s disease. New research that is measuring levels of GFAP, multi-differentiated UCH-L1, and S100B are advancing treatments for TBIs much earlier in the progression of the damage.

Inflammatory markers: 

TBI triggers a complex inflammatory response in the brain. Cytokines like interleukin-6 and tumor necrosis factor-alpha can be measured to assess the degree of inflammation. As the brain heals or bypasses damaged areas, the biomarker levels change. By monitoring these changes, the effectiveness of treatment can be measured.

Axonal injury markers: 

Neurofilament light chain is a marker of axonal damage, which is a common consequence of TBI. Elevated neurofilament light chain levels can indicate the severity of axonal injury and help predict long-term outcomes and treatments. The increases and decreases of levels of these markers allow scientists and doctors to see the immediate effectiveness of different treatments.

Imaging and Brain Mapping 

Advancement of imaging information about the injury to the brain can be enhanced by data mapping. While CT and MRI scans provide valuable structural information, they can fall short in capturing the full extent of injury, particularly in a diffuse axonal injury. Brain atlases offer a powerful tool for mapping and understanding the complex patterns of TBI. Brain atlases are standardized, three-dimensional representations of the brain that integrate data from multiple sources, including anatomical imaging, functional imaging, and even genetic information. Multiple healthy brains are scanned and the information gained is combined to create a generalized healthy brain structure.

These atlases can be used to:

Visualize injury patterns: 

By overlaying patient-specific imaging data onto a standardized brain atlas, clinicians can visualize the location and extent of injury in relation to specific brain structures.

Quantify injury severity: 

Brain atlases can be used to quantify the volume of damaged tissue and assess the impact of injury on specific brain networks.

Predict outcomes: 

By correlating injury patterns with clinical outcomes, brain atlases can help predict the likelihood of long-term neurological deficits.

Artificial Intelligence 

TBI 2025 will cover AI later this year as a separate topic in addition this overview. AI algorithms can be used to analyze large datasets of clinical and imaging data to identify patterns that predict outcomes and personalize treatment strategies. By building on known anatomy of the brain data mapping AI will provide opportunities for more individualized treatments and ensure best individual outcomes for each person’s TBI.

Conclusion 

The complexities of TBI pathology, together with the large variation of injury patterns make diagnosis and treatment challenging. Advancements in biomarker research offer promise in improving the diagnosis, treatment, and ultimately, the outcomes for individuals affected by TBI.