By some estimates, more than 300,000 US troops have suffered traumatic brain injury (TBI) in the current wars in Iraq and Afghanistan. Most of these injuries resulted from roadside bomb blasts and other explosives planted by insurgents. Lack of knowledge on how an explosive blast injures the brain has hampered efforts to treat those injuries. Now, two studies provide a potentially important insight, showing a mechanism that has not been taken into consideration.
The lead author of the study, bioengineer at Harvard University Kevin Kit Parker, said he had an interest in research. Parker moved his heart of attention to research on the brain after two tours in Afghanistan as a US Army infantry officer. "I saw some friends of mine get hit and thought," Okay, I'll take a look at this and see if I can get an angle on it. ""
Back at Harvard, Parker and his laboratory has designed a breath simulator for the cells. In a study published today in PLoS ONE , the researchers grew rat neurons in a culture dish, then joined an elastic polymer sheet. A high-precision motor gave a carefully calibrated to tug the sheet post neurons Parker mechanical forces calculated to be comparable to those produced by an explosion.
Through a microscope, the researchers found that the "explosion" caused swelling, rupture, and other signs of injury to axons and dendrites of neurons slender that send and receive signals from other neurons. A series of biochemical experiments found that the mechanical strength of disturbed proteins called integrins that help anchor cells to the protein scaffold that surrounds them. Integrins play a role in a wide range of biochemical signaling pathways, but Parker's team identified a particular channel which appears to play a role in injury to axons. A drug that blocks a component of this cascade called Rho kinase reduces damage to axons.
This result is intriguing given the recent results from damage to the white matter of the brain, which is composed of axons, Iraq veterans injured in the blasts, said Parker. Still, he warned that much more work is needed to see if these culture dish results are relevant to what happens in the brain of a soldier exposed to a blast. "It would be inappropriate to extrapolate from a flat head to a guy," says Parker.
A second document of the group Parker, published last week in the Proceedings of the national Academy of sciences , suggests that the same integrin signaling mechanism may contribute to vasospasm, another damaging process associated with TBI. in experiments with muscle cells in the wall of blood vessels, the researchers found that a sudden mechanical force returns a genetic switch in these cells, making them more likely to contract. this contraction would choke the blood supply wherever it occurs in the brain and aggravate an injury starving brain tissue of oxygen, said Parker.
"They duplicated in vitro a finding that was confusing for clinicians," says Jack Tsao, a neurologist and neuroscientist at the Uniformed Services University of science health in Bethesda, Maryland. Vasospasm usually results after a blow to the cause of the bleeding head in the space between the brain and the thin tissues that surround it. But in many troops with TBI shots, clinicians see the stroke symptoms as indicative of vasospasm, even when brain scans show no signs of bleeding. The new results provide a possible explanation for how this could happen, says Tsao.
"These are two very stylish documents," said David Hovda, a neuroscientist and director of the Brain Injury Research Center at the University of California, Los Angeles. Most research on the mechanisms of TBI focused on neurochemical changes on the wound site, such as metabolic alterations and ion imbalances within neurons, he said. But the new findings suggest a mechanism that has not been taken into consideration. The idea that integrins may play a role makes much sense and raises interesting possibilities for the treatment of TBI or minimize its effects with drugs given prophylactically, he said.
Hovda said he sees no reason why these mechanisms do not contribute to other types of brain damage also from car accidents to shaken baby syndrome. "I do not think it's specific to explosion."
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