Effect of valproic acid and injury on lesion size and endothelial glycocalyx shedding in a rodent model of isolated traumatic brain injury

BACKGROUND: In isolated traumatic brain injury (TBI), little is known about the endothelial response and the effects of endothelial glycocalyx shedding. We have previously shown that treatment with valproic acid (VPA) improves outcomes following TBI and hemorrhagic shock. In this model, we hypothesized that severe isolated TBI would cause shedding of the endothelial glycocalyx, as measured by serum syndecan-1 (sSDC-1) levels. We further hypothesized that VPA treatment would reduce this response and reduce lesion size volume. METHODS: Forty Sprague-Dawley rats were allocated to TBI + VPA (n = 8), TBI + saline vehicle control infusion (n = 8), sham + saline vehicle control infusion (n = 6), or sham + VPA (n = 8). TBI animals were subjected to severe controlled cortical impact and killed 6 hours after injury. VPA 300 mg/kg was given as an intravenous bolus 30 minutes after injury. Serum samples were analyzed for sSDC-1, and lesion size was determined on Nissl-stained cryosections. RESULTS: sSDC-1 was significantly elevated in injured compared with uninjured animals at 3 hours (p = 0.0009) and 6 hours (p = 0.0007) after injury. This effect was significantly more pronounced in the animals treated with VPA (p = 0.019) 3 hours after injury, in which sSDC-1 levels were also significantly inversely correlated with lesion size (Q = -0.55, p = 0.038). Lesion size was significantly smaller in TBI + VPA (40.45 mm(3) +/- 13.83 mm(3)) as compared with vehicle control (59.57 mm(3) +/- 16.83 mm(3)) (p = 0.023). CONCLUSION: Severe isolated TBI caused shedding of the endothelial glycocalyx. Treatment with VPA was associated with increased glycocalyx shedding and reduced lesion size volume in injured animal Copyright (C) 2014 by Lippincott Williams & Wilkins