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Mild, Repetitive Chronic Brain Injury

2016-02-29

Here is the abstract from a study on a mouse model of repeated mild brain injuries:

Mild traumatic brain injury (mTBI) is an emerging risk for chronic behavioral, cognitive, and neurodegenerative conditions. Athletes absorb several hundred mTBIs each year; however, rodent models of repeat mTBI (rmTBI) are often limited to impacts in the single digits. Herein, we describe the effects of 30 rmTBIs, examining structural and pathological changes in mice up to 365 days after injury. We found that single mTBI causes a brief loss of consciousness and a transient reduction in dendritic spines, reflecting a loss of excitatory synapses. Single mTBI does not cause axonal injury, neuroinflammation, or cell death in the gray or white matter. Thirty rmTBIs with a 1-day interval between each mTBI do not cause dendritic spine loss; however, when the interinjury interval is increased to 7 days, dendritic spine loss is reinstated. Thirty rmTBIs cause white matter pathology characterized by positive silver and Fluoro-Jade B staining, and microglial proliferation and activation. This pathology continues to develop through 60 days, and is still apparent at 365 days, after injury. However, rmTBIs did not increase β-amyloid levels or tau phosphorylation in the 3xTg-AD mouse model of Alzheimer disease. Our data reveal that single mTBI causes a transient loss of synapses, but that rmTBIs habituate to repetitive injury within a short time period. rmTBI causes the development of progressive white matter pathology that continues for months after the final impact.

In simpler terms, mice showed a pattern of inflammation in the brain after repeated mild injuries (severe enough to cause momentary loss of consciousness but no more) that differed from the changes seen after a single injury.  In the first injury, there is a loss of some dendritic spines (projections on the cell surface) that is repaired in 24 hours; the injury is mild enough that there is no death of nerve cells, inflammation, or axon (signaling end) injury.  In contrast, after repeated injuries suffered on a daily basis, thirty times, there is pathology seen in the brain layer that carries the signalling projections consisting of inflammation and increases in the number of active supporting cells (microglia).  These findings, in mice, show that repeated injuries without sufficient recovery time cause inflammation in the brain, not a sign of Alzheimer’s disease but equally serious.  Individuals with this type of injury have difficulty keeping their balance and clumsiness.

This is only an experiment with mice, but it shows that pathologically serious damage in the brain can be caused by repeated blows to the head that are relatively minor by themselves.  There is no reason to suspect that humans are any more resistant to microtrauma than mice.

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