Cerebral bioenergetics in hypovolemic shock: Mechanistic insights into the efficacy of EF24.

Since the primary determinant of mortality in hypovolemic shock is the host inflammatory response affecting multiple organs, addressing systemic inflammation is most vital in the critical first 60 min of blood loss. We investigated the effects EF24 (3,5-bis(2-flurobenzylidene)piperidin-4-one), an NF-kB inhibitor, on the status of rat brain suffering from severe (45%) blood loss because NF-kB activation contributes to neuronal cell death in prolonged ischemia. The hypovolemic rats were treated with EF24 solution (0.1ml, 0.4mg/Kg) within 1h of shock. No other resuscitation was provided; brain was collected at 6 h. Despite continued hypovolemia, EF24 reduced PARP and Casp 3 (proapototic proteins), HMGB1 (damage-associated molecular pattern), and increased Bcl2 (antiapoptotic) expression. Compared to vehicle-treated rats, EF24-treated rats showed significant (p<0.05) recovery of ATP, PCr and NAD/NADH ratio; Shock-induced changes in tissue citrate synthase activity, lactate and TBARS levels were not altered by...