Engineering Resilience in the Brain, Elastic Properties, Train Tracks and Crossties

Engineering Resilience in the Brain, Elastic Properties, Train Tracks and Crossties

With hundreds of billions of neurons, each with its own inner world of organelles and molecular components, understanding the fundamental wiring of the brain is a major undertaking, one that has received a commitment of at least $100 million worth of federal funding from the National Science Foundation (NSF), the National Institutes of Health and the Defense Advanced Research Projects Agency.

And with all of the brain's interconnected structures, protecting or repairing this complicated machine means thinking like an engineer.

Shenoy applies this approach to a problem very much in the public eye--traumatic brain injury. Even the mildest forms of TBI, better known as concussions, can do irreversible damage to the brain. More serious forms can be fatal.

With a background in mechanical engineering and materials science, one might think that Shenoy's contribution to this problem involves designing new helmets or other safety devices. Instead, he and his colleagues are uncovering the fundamental math and physics behind one of the core mechanisms of the injury: swelling in axons caused by damage to internal structures known as microtubules. These neural "train tracks" transport molecular cargo from one end of a neuron to another; when the tracks break, the cargo piles up and produces bulges in the axons that are the hallmark of fatal TBIs.

Armed with a better understanding of the mechanical properties of these critical structures, Shenoy and his colleagues are laying the foundations for drugs that could one day bolster neurons' reinforcing frames, making them more resilient when faced with a TBI-inducing impact.

Train tracks and crossties

The first step toward this understanding was resolving a paradox: Why were the microtubules, the stiffest elements of the axons, the parts that were breaking when loaded with the stress of a blow to the head?

A recent finding from Shenoy's team shows that the answer rests with a critical brain protein known as tau, which is implicated in several neurodegenerative diseases, including Alzheimer's. If microtubules are like train tracks, tau proteins are the crossties that hold them together. The protein's elastic properties help explain why rapid movement of the brain, whether on a football field or a car crash, leads to TBI.

Shenoy's colleague Douglas Smith, professor of neurosurgery in Penn's Perelman School of Medicine and director of the Penn Center for Brain Injury and Repair, had previously studied the mechanical properties of axons, subjecting them to strains of different forces and speeds.

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Engineering Resilience in the Brain, Elastic Properties, Train Tracks and Crossties