Neurology Central

Potential marker of non-reversible brain damage following concussion identified

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A new study carried out at the University of Pennsylvania (PA, USA) and the University of Glasgow (Glasgow, UK) has highlighted increases in the protein termed alpha II-spectrin N-terminal fragment (SNTF), following mild traumatic brain injury, (mTBI) as a potential marker of diffuse axonal injury, a specific type of brain damage often associated with cognitive impairments. The findings were published recently in Acta Neuropathologica and suggest that blood tests detecting SNTF could one day provide a method for diagnosing diffuse axonal injury and predicting cognitive impairment in concussion patients.

SNTF was identified as a potential biomarker by the study team due to its presence as a by-product of the axon-destroying enzyme activity associated with the mechanism of long-term brain damage following concussion. Previous work by study co-author Robert Siman (University of Pennsylvania) illustrated that in the days following concussion, blood levels of SNTF rose, reaching higher levels in individuals with greater cognitive dysfunction.

The current study looked to confirm this association between SNTF and axonal injury specifically in both experimental studies and in humans.

SNTF staining in brains with severe traumatic brain injury and consequently many pathological changes primarily identified only injured axons. Experimental concussion models also showed a similar pattern with SNTF, only identifying a subpopulation of degenerating axons in an environment where diffuse axonal injury is the main pathology.

The presence of APP, the current standard marker of axonal damage, was also assessed in the brain tissue and indicated that there was almost no overlap between damaged axons identified with APP and those stained with SNTF. The team suggest that this is due to the non-specificity of APP, marking all axons that are injured, including those with the potential to recover as opposed to only axons with non-reversible damage.

“Once an axon disconnects and degenerates, it’s never going to regrow to restore that communication pathway across the brain. We think it’s probably the end of the road for those axons” commented Douglas Smith, co-author on the study. “We’re starting to believe that the term ‘mild traumatic brain injury’ is an oxymoron. For some people there’s nothing mild about it.”

On the results, Siman commented: “This suggests that we may soon have a blood biomarker for concussion akin to the standard blood test used to detect cardiac damage from heart attacks. SNTF in the blood of a concussed individual may provide a specific diagnosis of diffuse axonal injury as well as the process of axonal degeneration.”

Source: Perelman School of Medicine, University of Pennsylvania press release

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