When the brain suffers severe shocks, such as those caused by the explosion of a nearby bomb, the delicate tissue is struck against the skull and, as a consequence, if the person survives, a temporary bruising, hemorrhage, or permanent traumatic brain injury, which can even lead to the early onset of Parkinson's or Alzheimer's.

Bioengineers from Harvard University have identified, for the first time, the mechanism of diffuse axonal injury and have explained why the cerebral vasospasm It is more common in brain injuries induced by explosions than in brain injuries suffered by civilians.

In the words of the principal investigator, Kevin Kit Parker, professor of bioengineering in School of Engineering and Applied Sciences (SEAS) of Harvard, and commander in the United States Army, "many young men and women of military service with brain injuries return, and we do not know how to help them."

Using the most advanced techniques in tissue engineering - essentially creating a living brain on a chip - biologists, physicists, engineers, and materials scientists collaborate to study brain injuries and their treatment. The results of the research, collected in two articles, published in 'Proceedings of the National Academy of Sciences' (PNAS) and in 'PLoS One', offer the most complete explanation to date of how mechanical forces can be translated into subtle Disastrous physiological changes for neurons of the brain and blood vessels.

Researchers have identified the cellular mechanism that initiates a diffuse axonal lesion, which offers guidance to research on therapeutic treatments. His studies show that integrins, proteins of the receptors integrated in the cell membrane, are the crucial link between external forces and internal physiological changes. Integrins connect the structural components of the cell (such as actin and other cytoskeletal proteins) with the extracellular matrix that binds the cells in the tissue. Together, this network of structural components is known as a complex of focal adhesion.

The forces unleashed by an explosion cause a chain reaction of molecular destruction within the nerve cells of the brain

Parker's research has shown that forces unleashed by a physical explosion alter the structure of the focal adhesion complex, which causes a chain reaction of molecular destruction within nerve cells of the brain.

Another part of the research carried out in Parker's laboratory has solved another mystery about traumatic brain injury, explaining why cerebral vasospasm, a dangerous remodeling of brain blood vessels, is more frequent in traumatic brain injury caused by the explosions than in other types of brain trauma.

As reported in the journal 'PNAS', the forces exerted on the arteries are different during an explosive charge than during a trauma from a blow. Subarachnoid hemorrhage, which can occur in severe head injuries, can cause vasospasm, but new research by Parker shows that only the force of an explosion can also cause vasospasm on its own.

An explosion creates an increase in blood pressure, which spreads to the walls of the blood vessels in the brain. For this study, Parker's bioengineers team built artificial arteries, made from living vascular cells, and used a special machine to stretch them in a rapid motion, simulating an explosion. In the 24 hours following the simulated explosion, the vascular tissues underwent hypercontraction and a complete phenotypic change, which altered the general function of the tissues. Both behaviors are characteristic of cerebral vasospasm.

The researchers observed that the Rho-ROCK signaling pathways play an important role in the behavior of the actin and the contraction of the cells. Parker's team found that Rho inhibition shortly after injury can mitigate the damaging effects of the explosion on the vascular system of the brain.


Concussion / Traumatic Brain Injury (TBI) (November 2019).