McGowan Institute for Regenerative Medicine
faculty member Patrick Kochanek, MD (pictured), director of the Safar Center for Resuscitation Research and professor in the Departments of Critical Care Medicine, Pediatrics and Anesthesiology, leads a team of University of Pittsburgh researchers trying to sort through the chaotic pathogenesis of the new, war-borne disease: traumatic brain injury (TBI). As reported by Reid Frazier in the Winter 2009/10 PittMed, armor, helmets, and better battlefield medicine have saved thousands of soldiers in the conflicts in Iraq and Afghanistan. (The killed-to-injured ratio in Iraq and Afghanistan is 1-to-10, compared to 1-to-2.5 for all other American wars.) But survivors are often severely injured. Soldiers with TBI induced by a blast suffer from headaches, dizziness, vertigo, gaze instability, and motion intolerance. Complicating care for these soldiers is the fact that blast TBI shares symptoms with post-traumatic stress disorder. Dr. Kochanek’s team is helping the Department of Defense by studying the neuropathology of blast.
Pitt researchers have found that, unlike its civilian cousin, blast TBI appears far more damaging to the synapses, axons, and dendrites of the brain—its white matter connective tissues and cables. These are the lines through which the electrochemical signaling of neurotransmission occurs.
“We’re getting an idea of how different this is from the conventional [civilian injury] model,” Kochanek says.
One culprit in the prevalence of axonal injury seems to be the increase in calcium signaling that occurs during blast TBI. Researchers have found that calcium pours through ion channels in injured neurons, releasing proteases suspected of cleaving proteins in the axons. (The prevalence of these cleaved proteins could serve as a biomarker for TBI on the battlefield.) So Safar researchers are looking at molecules known to moderate the calcium pathway—namely the immunosuppressants cyclosporine and tacrolimus (the now-ubiquitous antirejection drugs tested in organ transplant patients at Pitt). Other team members are researching drugs that target the mitochondria, which are sensitive to “excitatory” calcium signaling.
Blast TBI commonly occurs alongside other injuries—penetrating wounds, traumatically amputated limbs, hemorrhage. This polytrauma only deepens the severity of brain injury and the complication of treating it. Dr. Kochanek and his team of scientists are exploring several types of treatments since there is not likely one silver bullet.
Illustration: McGowan Institute for Regenerative Medicine.
Safar Center for Resuscitation Research
Bio: Dr. Patrick Kochanek