Treatment of head injury in mice, using a fructose 1,6-diphosphate and dimethyl sulfoxide combination

Mice were subjected to moderate (800 g/cm force) or severe (900 g/cm force) head injury and treated 5 minutes later with various compounds. Treatments consisted of intravenous administration of the following compounds: 1) fructose 1,6-diphosphate (FDP), 2) dimethyl sulfoxide (DMSO), 3) FDP + DMSO, and 4) vehicle nontreated. Sensory-motor evaluations 1 and 2 hours after 800 g/cm-force head injury showed that significant protection of motor function (grip test) was achieved with FDP + DMSO but not with treatment by either drug alone. Evaluation of mice following a severe 900-g/cm force injury demonstrated significant survival after treatment with FDP + DMSO but not with the vehicle or treatment by either of these agents alone. Histopathological morphometry indicated that cortical and hippocampal CA1 neurons were markedly protected from damage when mice were treated with combined FDP + DMSO. More modest protection of CA1 but not of cortical neurons was observed after treatment with DMSO alone but not after treatment with FDP alone or administration of the vehicle. These findings indicate that combining FDP with DMSO results in considerable synergy in protecting animals from sensory-motor loss and neuronal brain damage and in ultimate survival stemming from a moderate or severe closed head injury.