The delayed administration of dehydroepiandrosterone sulfate improves recovery of function after traumatic brain injury in rats.
The goal of the current study was to test the hypothesis that dehydroepiandrosterone-sulfate (DHEAS), a pro-excitatory neurosteroid, could facilitate recovery of function in male rats after delayed treatment following TBI. DHEAS has been found to play a major role in brain development and aging by influencing the migration of neurons, arborization of dendrites, and formation of new synapses. These characteristics make it suitable as a potential treatment to enhance neural repair in response to CNS injury. In our study, behavioral tests were conducted concurrently with DHEAS administration (0, 5, 10, or 20 mg/kg) starting seven days post-injury (PI). These assays included 10 days of Morris Water Maze testing (MWM; 7d PI), 10 days of Greek-Cross (GC; 21d PI), Tactile Adhesive Removal task (TAR; PI days: 6, 13, 20, 27, 34), and spontaneous motor behavior testing (SMB; PI days: 2, 4, 6, 12, 19, 26, 33). Brain-injured rats showed an improvement in performance in all tasks after 5, 10, or 20 mg/kg DHEAS. The most effective dose of DHEAS in the MWM was 10 mg/kg, while in the GC it was 20 mg/kg, in TAR 5 mg/kg, and all doses, except for vehicle, were effective at reducing injury-induced SMB hyperactivity. In no task did DHEAS-treated animals perform worse than the injured controls. In addition, DHEAS had no significant effects on behavioral performance in the sham-operates. These results can be interpreted to demonstrate that after a 7-day delay, the chronic administration of DHEAS to injured rats significantly improves behavioral recovery on both sensorimotor and cognitive tasks.
Brain Research Laboratory, Department of Emergency Medicine, Emory University, 1648 Pierce Drive, Atlanta, GA 30322, USA. swhoffm@emory.edu
Stuart W
SW
Hoffman
Sharad
S
Virmani
Robert M
RM
Simkins
Donald G
DG
Stein
D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy* / Q000503:physiopathology; D019314:Dehydroepiandrosterone Sulfate / Q000008:administration & dosage* / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology
D019314:Dehydroepiandrosterone Sulfate