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Penn researchers model a key breaking point involved in traumatic brain injury
Date:3/10/2014

retches a lot. But if you add stress to it rapidly, like in an impact, it breaks."

This behavior is because the strands of tau protein are coiled up and bonded to themselves in different places. Pulled slowly, those bonds can come undone, lengthening the strand without breaking it.

"The damage in traumatic brain injury occurs when the microtubules stretch but the tau doesn't, as they can't stretch as far," Shenoy said. "If you're in a situation where the tau doesn't stretch, such as what happens in fast strain rates, then all the strain will transfer to the microtubules and cause them to break."

With a comprehensive model of the tau-microtubule system, the researchers were able to boil down the outcome of rapid stress loading to equations with only a handful of variables. This mathematical understanding allowed the researchers to produce a phase diagram that shows the dividing line between strain rates that leave permanent damage versus safe and reversible loading and unloading of stress.

"Predicting what kind of impacts will cause these strain rates is still a complicated problem," Shenoy said. "I might be able to measure the force of the impact when it hits someone's head, but that force then has to make its way down to the axons, which depends on a lot of different things.

"You need a multiscale model, and our work will be an input to those models on the smallest scale."

In the longer term, knowing the parameters that lead to irreversible damage could lead to better understanding of brain injuries and diseases and to new preventive measures. It may even be possible to design drugs that alter microtubule stability and elasticity of axons in traumatic brain injury; Smith's group has demonstrated that treatment with the microtubule-stabilizing drug taxol reduced the extent of axon swellings and degeneration after stretch injury.

"Intriguingly, it may be no coincidence that tau is also the same prote
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Contact: Evan Lerner
elerner@upenn.edu
215-573-6604
University of Pennsylvania
Source:Eurekalert  

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