Differential effects of the anticonvulsant topiramate on neurobehavioral and histological outcomes following traumatic brain injury in rats.
The efficacy of topiramate, a novel therapeutic agent approved for the treatment of seizure disorders, was evaluated in a model of traumatic brain injury (TBI). Adult male rats were anesthetized (sodium pentobarbital, 60 mg/kg, i.p.), subjected to lateral fluid percussion brain injury (n = 60) or sham injury (n = 47) and randomized to receive either topiramate or vehicle at 30 min (30 mg/kg, i.p.), and 8, 20 and 32 h postinjury (30 mg/kg, p.o.). In Study A, memory was evaluated using a Morris water maze at 48 h postinjury, after which brain tissue was evaluated for regional cerebral edema. In Study B, animals were evaluated for motor function at 48 h and 1, 2, 3, and 4 weeks postinjury using a composite neuroscore and the rotating pole test and for learning ability at 4 weeks. Brains were analyzed for hemispheric tissue loss and hippocampal CA3 cell loss. Topiramate had no effect on posttraumatic cerebral edema or histologic damage when compared to vehicle. At 48 h, topiramate treatment improved memory function in sham but not brain-injured animals, while at one month postinjury it impaired learning performance in brain-injured but not sham animals. Topiramate significantly improved composite neuroscores at 4 weeks postinjury and rotating pole performance at 1 and 4 weeks postinjury, suggesting a potentially beneficial effect on motor function following TBI.
Hoover
Rachel C
RC
Head Injury Center, Department of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania 19103, USA.
Motta
Melissa
M
Davis
Jason
J
Saatman
Kathryn E
KE
Fujimoto
Scott T
ST
Thompson
Hilaire J
HJ
Stover
John F
JF
Dichter
Marc A
MA
Twyman
Roy
R
White
H Steve
HS
McIntosh
Tracy K
TK
D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D001929:Brain Edema / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology*; D005632:Fructose / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology*; D013997:Time Factors; D000077236:Topiramate; D016896:Treatment Outcome
D000927:Anticonvulsants; D000077236:Topiramate; D005632:Fructose