The Problem

Approximately 2.7 million American troops deployed to Iraq and Afghanistan since the beginning of the war on terror in 2001. The enemy used high explosives, usually improvised explosive devices (IEDs), against our forces, and these were responsible for the majority of combat casualties. Following exposure to blast traumatic brain injury (TBI), many service members developed persistent and debilitating neurobehavioral symptoms such as chronic headache, visual and balance difficulties, sleep disorder, problems concentrating and with memory, substance abuse, abrupt mood swings with periods of depression and despair, often leading to suicide. The presence of such prominent persistent, neuropsychiatric symptoms following blast exposure, accompanied by negative findings on routine neuroimaging (such as MRI exams), caused these episodes to be colloquially known to military physicians as the “invisible wound.” Despite an extensive literature on a variety of animal models, almost nothing was known about the pathophysiology of blast exposure on the human brain.

As Featured In


Dr. Dan Perl (Professor of Pathology and CNRM), and colleagues, identified a previously undescribed pattern of astroglial scarring upon microscopic examination of the brains of deceased U.S. service members with prominent persistent behavioral and neurologic symptoms following exposure to high impact explosions. In five service members who survived six months to nine years after blast exposure, the brain tissues revealed a distinct astroglial scarring pattern, and three additional service members who died days after IED attacks showed very early phases of astroglial scar formation in the same sites providing evidence for a pathophysiological link to damage caused by the actual blast event. In contrast, brain tissues from five deceased civilians with remote history of impact TBI (and small likelihood of blast exposure), five deceased civilians with history of substantial opioid use, and three control subjects with no TBI or opioid history failed to demonstrate the pattern of astroglial scarring as in the blast exposure cases.

Astroglial Scarring


Dr. Perl and colleagues concluded that the blast exposure cases showed a distinct and unique pattern of astroglial scarring at interface neuroanatomical boundaries, particularly between brain parenchyma and fluids (cerebrospinal and blood) and at junctions between gray and white matter.

Dr. Perl published these findings in Lancet Neurology (Lancet Neurol. 15:944-953, 2016), where he conjectures that the interface astroglial scarring pattern within brain could explain many of the symptoms reported in service members exposed to high impact explosions. These findings also challenge the medical community to reassess current clinical diagnostic and treatment paradigms for blast-exposed patients, particularly within the disciplines of neurology and psychiatry. For this landmark publication, Dr. Perl has been actively solicited by the lay press and military leaders for his advice, opinions, and help.