Intensity- and Interval-Specific Repetitive Traumatic Brain Injury Can Evoke Both Axonal and Microvascular Damage

Abstract In the experimental setting several investigators have recently reported exacerbations of the burden of axonal damage and other neuropathological changes following repetitive traumatic brain injuries (TBI) that were sustained at intervals from hours to days following the initial insult. These same studies also revealed that prolonging the interval between the first and second insult led to a reduction in the burden of neuropathological changes and/or their complete elimination. Although demonstrating the capability of repetitive TBI to evoke increased axonal and other neuropathological changes, these studies did not address the potential for concomitant microvascular dysfunction or damage, although vascular dysfunction has been implicated in the second-impact syndrome. In this study we revisit the issue of repetitive injury in a well-controlled animal model in which the TBI intensity was bracketed from subthreshold to threshold insults, while the duration of the intervals between the injuries var...