Current State and Prospects of Development of Blood-based Biomarkers for Mild Traumatic Brain Injury

Abstract

Highlights• There are many unresolved clinical problems about mild traumatic brain injury (mTBI) such as a low sensitivity of standard neuroimaging studies, and absence of reliable predicting models.• It is very difficult to diagnose mTBI in symptomatic patients in the absence of witnesses, clear signs of head trauma, and abnormalities on neuroimaging.• Blood proteins have great potential as diagnostic and prognostic biomarkers of mTBI.• Technological advances in the targeted proteomics are expected to realize the clinical potential of blood-based protein biomarkers. ABSTRACTThe current understanding of the pathophysiology of mild traumatic brain injury (mTBI) is, without doubt, incomplete. Nevertheless, we tried to summarize the state-of-the-art explanation of how the brain is continuously injured even after a single impact. We also reviewed the real struggle of diagnosing mTBI, which culminated in showing the potential of blood-based biomarkers as an alternative or complementary way to overcome this difficulty. Pathophysiology of mTBI is subdivided into primary and secondary injuries. Primary injury is caused by a direct impact on the head and brain. Secondary injury refers to the changes in energy metabolism and protein synthesis/degradation resulting from the biochemical cascades as follows; calcium influx, mitochondrial dysfunction, fractured microtubules, and Wallerian degeneration, neuroinflammation, and toxic proteinopathy. Since the diagnosis of mTBI is made through the initial clinical information, it is difficult and inaccurate to diagnose mTBI without the absence of a witness or sign of head trauma. Blood-based biomarkers are expected to play an important role in diagnosing mTBI and predicting functional outcomes, due to their feasibility and the recent progress of targeted proteomics techniques (i.e., liquid chromatography tandem mass spectrometry [LC-MS/MS]).

Transcranial direct current stimulation combined with amantadine in repetitive mild traumatic brain injury in rats

“…GFAP is a protein found only in the central nervous system. GFAP levels are increased when astrocytes are damaged [ 30 ]. A low GFAP integral intensity indicates a decrease in reactive astrocytosis, which can play a neurotoxic role and aggravate neural death [ 31 , 32 ] Previous study showed that GFAP could determine patients with mTBI with subtle injuries detected only through MRI [ 33 ] 30 days after all treatments and evaluations (Day 36), 12 rats (3 rats from each group were randomly selected) were euthanized by carbon dioxide inhalation using an approved standard protocol.…”