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 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.
Bentzer
P
P
Department of Physiological Sciences, Lund University, Sweden. peter.bentzer@mphy.lu.se
Mattiasson
G
G
McIntosh
T K
TK
Wieloch
T
T
Grande
P O
PO
D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology; D011464:Epoprostenol / Q000008:administration & dosage*; D008297:Male; D019579:Neocortex / Q000187:drug effects* / Q000293:injuries / Q000473:pathology; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley
D010975:Platelet Aggregation Inhibitors; D011464:Epoprostenol