Treatment of Head Injury in Mice, Using a Fructose 1,6-Diphosphate and Dimethyl Sulfoxide Combination

Abstract

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.

Efficacy of a Metalloproteinase Inhibitor in Spinal Cord Injured Dogs

“…Finally, DMSO, when co-administered with a candidate therapeutic, offers potential for synergism, by acting through separate and/or overlapping pathways. While we found no evidence of this in the current study, others have reported synergism in a model of brain ischemia where DMSO was either combined with fructose 1,6-disphosphate, an intermediate of anaerobic metabolism, or prostacyclin (PG I2 ) which blocks aggregation of platelets and functions as a vasodilator [12], [54].…”

“…In summary, while this study and others [12], [13], [52], [54] underscore the potential utility of DMSO for the treatment of brain and SCI, there remain conflicting reports about the efficacy of DMSO. This is illustrated in recent studies reporting either no effects or reduced performance on behavioral tests after traumatic brain injury [55] and others suggesting improved learning ability in cerebellar mutant Lurcher mice [56].…”

“…While DMSO is commonly used as a vehicle to increase solubility of a drug, it has been reported to have neuroprotective properties in traumatic brain injury and SCI [12], [13]. The putative neuroprotective activity of DMSO is thought to arise from its ability to block voltage-sensitive sodium channels and calcium influx into cells, and mitigate opening of ionotropic channels that are activated by glutamate [14].…”

Serofendic Acid, a Sulfur-Containing Diterpenoid Derived from Fetal Calf Serum, Attenuates Reactive Oxygen Species-Induced Oxidative Stress in Cultured Striatal Neurons

“…In addition to its activity as a scavenger of ⅐OH (Reuvers et al, 1973), DMSO has been reported to regulate cell differentiation (Friend et al, 1971;Collins et al, 1978;Isom et al, 1985), the cell cycle (Darling et al, 1989;Sawai et al, 1990;Srinivas et al, 1991), and apoptosis (Marthyn et al, 1998;Fiore and Degrassi, 1999). Administration of DMSO to rodents and primates can reduce neuronal injury in experimental models of ischemic (Albin et al, 1983;de la Torre, 1983;Phillis et al, 1998) and traumatic brain injury (de la Torre, 1983(de la Torre, , 1995, improve cerebral blood flow after injury (de la Torre, 1983), and reduce intracranial pressure after head trauma (Karaca et al, 1991). It is conceivable that the DMSO structure plays important roles in the cellular, molecular, and pharmacological effects of serofendic acid.…”

Matrix Metalloproteinases as a Therapeutic Target to Improve Neurologic Recovery After Spinal Cord Injury

“…In this study, we have used dimethyl sulfoxide (DMSO) in combination with GM6001 [10,11]. While DMSO is commonly used as a vehicle to increase solubility of a drug, it has been reported to have neuroprotective properties in traumatic brain injury and SCI [12,13]. The putative neuroprotective activity of DMSO is thought to arise from its ability to block voltage-sensitive sodium channels and calcium influx into cells, and mitigate opening of ionotropic channels that are activated by glutamate [14].…”