Evaluation of combined fibroblast growth factor-2 and moderate hypothermiatherapy in traumatically brain injured rats

Both the exogenous administration of fibroblast growth factor-2 (FGF-2) or the induction of moderate hypothermia have been shown to attenuate histopat hology and improve functional outcome after traumatic brain injury (TBI). S ince combined therapeutic strategies may be more beneficial than single the rapies, we examined the potential synergistic effect of FGF-2 combined with moderate hypothermia treatment induced 10 min after TBI on functional and histological outcome following controlled cortical impact (CCI) injury. Fif ty male Sprague-Dawley rats were randomized to one sham and four CCI treatm ent groups: Sham+vehicle (VEH); FGF-2 (45 mug/kg/h for 3 h i.v.)+Normotherm ia (37 +/- 0.5 degreesC); FGF-2+Hypothermia (32 +/- 0.5 degreesC for 3 h); VEH+Norm; VEH+Hypo. Vestibulomotor performance on the beam balance and beam -walk (BW) tasks on post-operative days 1-5 and spatial memory acquisition in the Morris water maze (MWM) on days 14-18 were assessed. After 4 weeks s urvival, histological evaluations (CA(1) and CA(3) cell counts and lesion v olume) were performed. MWM performance improved in all treatment groups, bu t combined treatment was not more efficacious than either alone. The FGF-2Hypo group performed significantly better than the other injured treatment groups in the BW task. Lastly, no significant group differences in beam bal ance or histological outcome were observed. These data suggest a suboptimal and incomplete synergy of combined FGF-2 and hypothermia treatment. These data may indicate that either our dose of FGF-2 or combination therapy was not optimized in our model. (C) 2000 Elsevier Science BN. All rights reserv ed.