ADMINISTRATION OF VALPROIC ACID IN CLINICALLY APPROVED DOSE IMPROVES NEUROLOGIC RECOVERY AND DECREASES BRAIN LESION SIZE IN SWINE SUBJECTED TO HEMORRHAGIC SHOCK AND TRAUMATIC BRAIN INJURY.

Traumatic brain injury (TBI) and hemorrhage remain the leading causes of death after trauma. We have previously shown that a dose of Valproic Acid (VPA) at (150 mg/kg) can decrease brain lesion size & hasten neurologic recovery. The current FDA approved dose of VPA is 60 mg/kg. We evaluate neurologic outcomes and brain lesion size of a single dose of VPA at a level currently within FDA approved dose in swine subjected to TBI and hemorrhagic shock.
Swine (n=5/group) were subjected to TBI and 40% blood volume hemorrhage. Animals remained in shock for 2 hours before randomization to normal saline (NS) resuscitation alone (Control), NS + VPA 150 mg/kg (VPA 150), or NS +VPA 50 mg/kg (VPA 50). Neurologic severity scores (NSS; Range 0-32) were assessed daily for 14 days and brain lesion size was measured via MRI on post injury day (PID) 3.
Shock severity and laboratory values were similar in all groups. VPA treated animals demonstrated significantly less neurologic impairment on PID1 and returned to baseline faster (PID 1 mean NSS score: control = 22 ± 3 versus VPA 150mg/kg = 8 ± 7 or VPA 50 mg/kg = 6 ± 6; p = 0.02 and 0.003). VPA treated animals had significantly smaller brain lesion sizes (mean volume in mm: Control =1268.0 ± 241.2 versus VPA 150 mg/kg =620.4 ± 328.0 or VPA 50 mg/kg =438.6 ± 234.8; p= 0.007 and 0.001).
In swine subjected to TBI and hemorrhagic shock, VPA treatment, in a dose that is approved for clinical use, decreases brain lesion size & reduces neurologic impairment compared to resuscitation alone.
Therapeutic, level 5.