Infusion of prostacyclin following experimental brain injury in the rat reduces cortical lesion volume

Endothelial-derived prostacyclin is an important regulator of microvascular function, and its main actions are inhibition of platelet/leukocyte aggreg ation and adhesion, and vasodilation. Disturbances in endothelial integrity following traumatic brain injury (TBI) may result in insufficient prostacy clin production and participate in the pathophysiological sequelae of brain injury. The objective of this study was to evaluate the potential therapeu tic effects of a low-dose prostacyclin infusion on cortical lesion volume, CA3 neuron survival and functional outcome following TBI in the rat. Anesth etized animals (sodium pentobarbital, 60 mg/kg, i.p.) were subjected to a l ateral fluid percussion brain injury (2.5 atm) or sham injury. Following TB I, animals were randomized to receive a constant infusion of either prostac yclin (1 ng/kg . min(-l) i.v.) or vehicle over 48 h. All sham animals recei ved vehicle (n = 6). Evaluation of neuromotor function, lesion volume, and CA3 neuronal loss was performed blindly. By 7 days postinjury, cortical les ion volume was significantly reduced by 43% in the prostacyclin-treated gro up 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 T BI) between the prostacyclin- and vehicle-treated groups. We conclude that prostacyclin in a low dose reduces loss of neocortical neurons following TB I and may be a potential clinical therapeutic agent to reduce neuronal cell death associated with brain trauma.