Traumatic brain injury (TBI) is a significant risk factor for the development of neurodegenerative diseases, which may involve diverse underlying pathologies. Chronic traumatic encephalopathy (CTE), in particular, is closely linked to repetitive mild TBI (mTBI) and is pathologically characterized by the accumulation of hyperphosphorylated tau into neurofibrillary tangles (NFTs). CTE may be suspected when individuals experience progressive declines in behavior, cognition, and memory following repeated mTBI episodes. Exposure to blast overpressure from improvised explosive devices (IEDs) has been implicated as a potential precursor to CTE among veterans of the Iraq and Afghanistan conflicts. This study investigates biomarker signatures in rats subjected to repetitive low-level blast exposure who develop chronic anxiety-related traits, as well as in human veterans exposed to IED blasts during deployment and presenting with behavioral, cognitive, or memory complaints.
Rats exposed to repetitive low-level blasts exhibited abnormal accumulation of hyperphosphorylated tau in neuronal perikarya and perivascular astroglial processes. Using positron emission tomography (PET) with the [18F]AV1451 (flortaucipir) tau ligand, five out of ten veterans displayed excessive retention of [18F]AV1451 at the white/gray matter junction in frontal, parietal, and temporal brain regions—consistent with the typical localization of CTE-associated tauopathy.RPL10 Antibody Protocol Additionally, elevated levels of neurofilament light (NfL) chain protein were detected in the plasma of veterans showing increased [18F]AV1451 retention. These findings suggest a biological link between blast injury, tau pathology, and neuronal damage. Further research is needed to determine whether clinical, neuroimaging, and fluid biomarker profiles can enhance the early diagnosis of long-term neuropsychiatric sequelae resulting from mTBI.
The study utilized a well-established and validated battlefield-relevant rat model of blast-induced mTBI that exhibits chronic anxiety-like behaviors. In parallel, a clinical biomarker investigation was conducted on human veterans with histories of multiple blast exposures and persistent post-concussive symptoms. The integration of animal and human data provides a comprehensive approach to understanding the neuropathological consequences of blast trauma. Immunohistochemical analysis revealed increased phosphorylation of tau at Thr181 in the anterior cortex and hippocampus of rats at 6 weeks and 10 months post-blast exposure. Notably, this phosphorylation was accompanied by somatodendritic redistribution of tau and abnormal perivascular accumulation in astroglial processes—features previously associated with CTE pathology.
In humans, PET imaging with [18F]AV1451 identified excess ligand retention in 50% of the veteran cohort, primarily localized to the depths of cortical sulci at the white/gray matter interface—a hallmark of CTE. No such retention was observed in healthy comparison subjects. Plasma NfL levels were significantly higher in veterans with positive [18F]AV1451 scans compared to those without, suggesting that NfL may serve as a peripheral indicator of ongoing neuronal injury.BTK Antibody Biological Activity These results support the hypothesis that blast exposure can trigger pathological changes resembling CTE, detectable both in animal models and living humans.PMID:35169028
MRI and cortical diffusivity analysis further supported these findings. While structural MRI revealed minimal abnormalities in most veterans, cortical diffusivity analysis indicated microstructural disruption in several cases, particularly among those with elevated [18F]AV1451 retention. This suggests that subtle changes in tissue integrity may precede overt structural damage and could represent an early biomarker of neurodegeneration.
Despite limitations including small sample size and the absence of postmortem confirmation, this study offers compelling evidence that blast-related mTBI can lead to tauopathy and neuronal injury detectable in vivo. The convergence of findings across species strengthens the case for using combined multimodal biomarkers—PET imaging, blood-based NfL, and advanced neuroimaging—for early detection and monitoring of CTE-like conditions. Future studies should focus on larger cohorts, longitudinal assessments, and validation through autopsy to solidify diagnostic criteria for CTE during life.MedChemExpress (MCE) offers a wide range of high-quality research chemicals and biochemicals (novel life-science reagents, reference compounds and natural compounds) for scientific use. We have professionally experienced and friendly staff to meet your needs. We are a competent and trustworthy partner for your research and scientific projects.Related websites: https://www.medchemexpress.com
