Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Penn Researchers Model a Key Breaking Point Involved in Traumatic Brain Injury

11.03.2014

Even the mildest form of a traumatic brain injury, better known as a concussion, can deal permanent, irreparable damage. Now, an interdisciplinary team of researchers at the University of Pennsylvania is using mathematical modeling to better understand the mechanisms at play in this kind of injury, with an eye toward protecting the brain from its long-term consequences.

Their recent findings, published in the Biophysical Journal, shed new light on the mechanical properties of a critical brain protein and its role in the elasticity of axons, the long, tendril-like part of brain cells. This protein, known as tau, helps explain the apparent contradiction this elasticity presents. If axons are so stretchy, why do they break under the strain of a traumatic brain injury?    


The protein tau acts as "cross ties" for the microtuble "train tracks" that run the length of the axon.

Tau’s own elastic properties reveal why rapid impacts deal permanent damage to structures within axons, when applying the same force more slowly causes them to safely stretch. This understanding can now be used to make computer models of the brain more realistic and potentially can be applied toward tau-related diseases, such as Alzheimer’s.

The team consists of Vivek Shenoy, professor of materials science and engineering in the School of Engineering and Applied Science, Hossein Ahmadzadeh, a member of Shenoy’s lab, and Douglas Smith, professor of neurosurgery in Penn’s Perelman School of Medicine and director of the Penn Center for Brain Injury and Repair

“One of the main things you see in the brains of patients who have died because of a TBI is swellings along the axons,” Shenoy said. “Inside axons are microtubules, which act like tracks for transporting molecular cargo along the axon. When they break, there’s an interruption in the flow of this cargo and it starts to accumulate, which is why you get these swellings.”  

Smith had previously studied the mechanical properties of axons as a whole. By patterning axons in culture in parallel tracts, Smith and his colleagues could apply a stretch to the axons at different forces and speeds and measure how they responded.

“What we saw is that with slow loading rates, axons can stretch up to at least 100 percent with no signs of damage,” Smith said. “But at faster rates, axons start displaying the same swellings you see in the TBI patients. This process occurs even with relatively short stretch at fast rates. So the rate at which stretch is applied is the important component, such as occurs during rapid movement of the brain and stretching of axons due to head impact from a fall, assault or automobile crash.”

This observation still did not explain to researchers why microtubules, the stiffest part of the axon, were the parts that were breaking. To solve that puzzle, the researchers had to delve even deeper into their structure.

Microtubules are closely packed together inside axons, somewhat like a bundle of straws. Binding the individual straws together is the protein tau. Other biophysical modelers had previously accounted for the geometry and elastic properties of the axon during a stretching injury based on Smith’s work but did not have good data for representing tau’s role in the overall behavior of the system when it is loaded with stress over different lengths of time. 

“You need to know the elastic properties of tau,” Shenoy said, “because when you load the microtubules with stress, you load the tau as well. How these two parts distribute the stress between them is going to have major impact on the system as a whole.”

Shenoy and his colleagues had a sense of tau’s elastic properties but did not have hard numbers until a 2011 experiment from a Swiss and German research team physically stretched out lengths of tau by plucking it with the tip of an atomic force microscope.

“This experiment demonstrated that tau is viscoelastic,” Shenoy said. “Like Silly Putty, when you add stress to it slowly, it stretches 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 protein that forms neurofibrillary tangles, one of the hallmark brain pathologies of chronic traumatic encephalopathy, or CTE, which is linked to a history of concussions and higher levels of TBI,” said Smith. “Uncovering the role of tau at the time of trauma may provide insight into how it is involved in long-term degenerative processes.”

The research was supported by the National Science Foundation, National Institutes of Health and Department of Defense.

Evan Lerner | EurekAlert!
Further information:
http://www.upenn.edu

Further reports about: Brain TBI Traumatic axons break damage elastic elasticity injury microtubules properties strain

More articles from Health and Medicine:

nachricht Organ-on-a-chip mimics heart's biomechanical properties
23.02.2017 | Vanderbilt University

nachricht Researchers identify cause of hereditary skeletal muscle disorder
22.02.2017 | Klinikum der Universität München

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>