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.
Hoffman
Stuart W
SW
Brain Research Laboratory, Department of Emergency Medicine, Emory University, 1648 Pierce Drive, Atlanta, GA 30322, USA. swhoffm@emory.edu
Virmani
Sharad
S
Simkins
Robert M
RM
Stein
Donald G
DG
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