Abstract # 2065 Markers of peripheral immune cells are increased in regions of blood-brain barrier disruption after repetitive blast injury

Abstract

Cycles of blood-brain barrier (BBB) disruption have been observed in a variety of rodent brain injury models. Changes in BBB permeability are correlated with pro-inflammatory cytokine production and brain infiltration of peripheral leukocytes. Whether the influx of peripheral leukocytes through a permeable BBB affords prolonged neuroprotection, or promotes detrimental changes to the anatomical site of entry remains to be elucidated. In a mouse model of blast-induced traumatic brain injury (TBI), we observed brain-region specific BBB permeability to radiolabeled albumin at 72 h. Moreover, we measured an increase in pro-inflammatory tumor necrosis factor alpha (TNF α ) protein expression and mRNA abundance in brain regions vulnerable to BBB disruption. The nitric oxide synthase inhibitor N(G)-nitro- l -arginine methyl ester (L-NAME) attenuated TNF α levels and abrogated albumin permeability. We hypothesize that leukocyte infiltration into vulnerable brain regions after TBI may also be mediated by nitric oxide dependent mechanisms. Using flow cytometry, we measured an increase of blood-derived monocytes (Ly6C/G-high and CD45-high) and T-cells (CD3+ and CD4+) in brain regions vulnerable to BBB disruption at 72 h post-TBI. The physiological process of leukocyte infiltration could be driven by nitric oxide dependent mechanisms, which could be exploited, at the right time, to assist in chronic neurotrauma resolution.