The Role of Age and Model Severity on Cortical Vascular Response Following Traumatic Brain Injury

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Virginia Tech


Traumatic brain injury (TBI) is a growing health concern worldwide that affects a broad range of the population. As TBI is the leading cause of disability and mortality in children, several pre-clinical models have been developed using rodents at a variety of different ages; however, key brain maturation events are overlooked that leave some age groups more or less vulnerable to injury. Thus, there has been a large emphasis on producing relevant animal models to elucidate molecular pathways that could be of therapeutic potential to help limit neuronal injury and improve behavioral outcome. TBI involves a host of different biochemical events, including disruption of the cerebral vasculature and breakdown of the blood brain barrier (BBB) that exacerbate secondary injuries. A better of understanding of the mechanism(s) underlying cerebral vascular regulation will aid in establishing more effective treatment strategies aimed at improving cerebral blood flow restoration and preventing further neuronal loss. Our studies reveal an age-at- injury dependence on the Angiopoetin-Tie2 axis, which mediates neuroprotection in a model of juvenile TBI following cortical controlled impact (CCI) that is not seen in adult mice. The protection observed was mediated, in part, by the microvascular response to CCI injury and prompted further detailed analysis of the larger arteriole network across several mouse strains and models of TBI. Our second study revealed both a model and species dependent effect on a specialized network of arteriole vessels, called collaterals after trauma. We demonstrated that a repetitive mild TBI (rmTBI) can induce collateral remodeling in C57BL/6 but not CD1 mice; however, CCI injury had no effect on collateral changes in either strain. Together, these findings demonstrate an age-dependent and species/model dependent effect on vascular remodeling that highlights the importance of individualized therapeutics to TBI.



traumatic brain injury, arteriole vessels, angiopoietin, endothelial cell, blood brain barrier, juvenile TBI