Sequential pharmacotherapy with magnesium chloride and basic fibroblast growth factor after fluid percussion brain injury results in less neuromotor efficacy than that achieved with magnesium alone.
Combinational pharmacotherapy with individually efficacious agents is a potential strategy for the treatment of traumatic central nervous system (CNS) injury. Basic fibroblast growth factor (bFGF) has been shown to be neuroprotective against excitotoxic, ischemic, and traumatic injury to the CNS, while acute posttraumatic treatment with magnesium (Mg2+) has been shown to decrease the motor and cognitive deficits following experimental brain injury. In this study, bFGF and Mg2+ were evaluated separately and in combination to assess their potential additive effects on posttraumatic neurological recovery and histological cell loss (lesion volume). Twenty minutes after fluid percussion (FP) brain injury of moderate severity (2.2-2.4 atm), anesthetized rats received a 15-min intravenous infusion of either 125 mumol of MgCl2 or vehicle, followed 5 min later by a 24-h constant intravenous infusion of either bFGF (16 micrograms/h) or vehicle. Injured animals had a significant motor deficit when compared to sham (uninjured) animals at both 48 h and 7 days postinjury. At 48 h postinjury, there were no significant differences among injured animals when compared by treatment. By 7 days postinjury, injured animals treated with MgCl2 alone displayed significantly improved motor function when compared to brain-injured, vehicle-treated animals (p < 0.05). Animals treated with either bFGF alone or a combination of MgCl2 and bFGF displayed no significant neurological improvement relative to vehicle-treated injured animals at 7 days. No effect of any drug treatment of combination was observed on the extent of the postinjury lesion volume in the injured cortex. These results suggest that caution must be exercised when combining "cocktails" of potentially neuroprotective compounds in the setting of traumatic brain injury.
Guluma
K Z
KZ
Department of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia, USA.
Saatman
K E
KE
Brown
A
A
Raghupathi
R
R
McIntosh
T K
TK
D000704:Analysis of Variance; D000818:Animals; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000293:injuries / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000627:therapeutic use*; D015636:Magnesium Chloride / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D009069:Movement Disorders / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D013997:Time Factors; D016896:Treatment Outcome
D018696:Neuroprotective Agents; D015636:Magnesium Chloride; D016222:Fibroblast Growth Factor 2