@article{ref1,
title="Repeated primary blast injury causes delayed recovery, but not additive disruption, in an in vitro blood-brain barrier model",
journal="Journal of neurotrauma",
year="2014",
author="Hue, Christopher Donald and Cao, Siqi and Bass, Cameron 'dale' and Meaney, David and Morrison, Barclay",
volume="31",
number="10",
pages="951-960",
abstract="Recent studies have demonstrated increased susceptibility to breakdown of the cerebral vasculature associated with repetitive traumatic brain injury. We hypothesized that exposure to two consecutive blast injuries would result in exacerbated damage to an in vitro model of the blood-brain barrier (BBB) compared to exposure to a single blast of the same severity. However, contrary to our hypothesis, repeated mild or moderate primary blast delivered within 24 or 72 hours did not significantly exacerbate reductions in trans-endothelial electrical resistance (TEER) across a brain endothelial monolayer compared to sister cultures receiving a single exposure of the same intensity. Permeability of the barrier to a range of different-sized solutes remained unaltered after single and repeated blast, supporting that the effects of repeated blast on BBB integrity were not additive. Single blast exposure significantly reduced immunostaining of ZO-1 and claudin-5 tight junction proteins, but subsequent exposure did not cause additional damage to tight junctions. Although repeated blast did not further reduce TEER, the second exposure delayed TEER recovery in BBB cultures. Similarly, recovery of hydraulic conductivity through the BBB was delayed by a second exposure. Extending the inter-injury interval to 72 hours, the effects of multiple injuries on the BBB were found to be independent given sufficient recovery time between consecutive exposures. Careful investigation of the effects of repeated blast on the BBB will help identify injury levels and a temporal window of vulnerability associated with BBB dysfunction, ultimately leading to improved strategies for protecting warfighters against repeated blast-induced disruption of the cerebral vasculature.<p /> <p>Language: en</p>",
language="en",
issn="0897-7151",
doi="10.1089/neu.2013.3149",
url="http://dx.doi.org/10.1089/neu.2013.3149"
}