The role of pluronic F68 and F127 combined growth factors and stem cells in reducing ketamine induced neurotoxicity

Ketamine is an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist which is used as human and animal medicine as an injectable anesthetic. Recently it was shown that Ketamine gives rise to neurotoxicity and cell death during surgical operations. Furthermore, long-term Ketamine administration increases the number of hyperphosphorylated tau positive cells, which is a hallmark of Alzheimer?s Disease. In this study, we aimed to decrease the Ketamine induced neurotoxicity on SH-SY5Y neuroblastoma and primary mix brain culture cells applying several growth factors, namely; Fibroblast Growth Factor-2 (FGF-2) Insulin-Like Growth Factor-1 (IGF-1), Brain-Derived Neurotrophic Factor (BDNF), Nerve Growth Factor (NGF), Vascular Endothelial Growth Factor (VEGF) and stem cell conditioned medium in the presence of Pluronic F68 and F127. Moreover the effect of stem cells on this toxicity was investigated using stem cell co-culture system. Pluronics used in this study were reported to act as drug delivery reagents and membrane stabilizers which are important agents in the treatment neurodegenerative diseases. The stem cells used in this study were derived from Human Tooth Germs and not only comprise mesenchymal stem cell properties but also possess the capacity to differentiate into neurogenic cells. Our results demonstrated that the administration of either stem cell conditioned medium or direct stem cells in co-culture system protect cells from the Ketamine induced toxicity. The growth factors tested were also protective on SH-SY5Y and primary mix brain culture cells to some extent. Both stem cells and growth factors administered in combination with the Pluronics F68 and F127 were much more effective in reducing the neurotoxicity. These data suggested that stem cells and growth factors play an important role in ameliorating the adverse effects of Ketamine and the administration of Pluronics might increase the protection and healing of cells from the Ketamine induced stress. Pluronics can also provide an alternate approach for the treatment of other neurodenerative diseases.