Endothelial-derived
prostacyclin is an important regulator of microvascular function, and its main actions are inhibition of platelet/leukocyte aggregation and adhesion, and vasodilation. Disturbances in endothelial integrity following
traumatic brain injury (TBI) may result in insufficient
prostacyclin production and participate in the pathophysiological sequelae of
brain injury. The objective of this study was to evaluate the potential
therapeutic effects of a low-dose
prostacyclin infusion on cortical lesion volume, CA3 neuron survival and functional outcome following TBI in the rat. Anesthetized animals (
sodium pentobarbital, 60 mg/kg, i.p.) were subjected to a lateral fluid percussion
brain injury (2.5 atm) or
sham injury. Following TBI, animals were randomized to receive a constant infusion of either
prostacyclin (1 ng/kg x min(-1) i.v.) or vehicle over 48 h. All
sham animals received vehicle (n = 6). Evaluation of neuromotor function, lesion volume, and CA3 neuronal loss was performed blindly. By 7 days postinjury, cortical lesion volume was significantly reduced by 43% in the
prostacyclin-treated group as compared to the vehicle treated group (p < 0.01; n = 12
prostacyclin, n = 12 vehicle). No differences were observed in neuromotor function (48 h and 7 days following TBI), or in hippocampal cell loss (7 days following TBI) between the
prostacyclin- and vehicle-treated groups. We conclude that
prostacyclin in a low dose reduces loss of neocortical neurons following TBI and may be a potential clinical therapeutic agent to reduce neuronal cell death associated with
brain trauma.