Buffers and H2O2 reduce neuronal death and/or enhance differentiation of neurons and astrocytes in dissociated mouse brain cultures.
Tissue of the mammalian central nervous system (CNS) undergoes complex and uncoordinated pathological responses upon injury. Efforts to develop pharmacological approaches to achieve functionally meaningful regeneration largely have been unsuccessful. Assuming that anoxia and drop in tissue H are initiating factors in most pathological sequences consequent to CNS injury, we studied the effects of increasing the buffering and oxygenating capacities of the medium on dissociated embryo brain cultures. The presence of H2O2 in the medium led to greatly enhanced neuronal survival and/or differentiation. Increased buffering capacity favored enhanced neurite outgrowth with remarkable elongation of fibers. A combination of the two gave a synergistic effect in which both of the above responses were seen. Both buffers and H2O2 enhanced astrocytic differentiation and extension of processes while reducing DNA synthesis. The results favor the view that attempts to encourage self-repair in CNS tissue or to enhance repair of CNS damage with potential therapeutic agents or procedures should be carried out in the context of a near optimal environment in which, at the least, pH and pO2 values are stably maintained within normal operational limits.
D000818:Animals; D001253:Astrocytes / Q000032:analysis / Q000187:drug effects* / Q000648:ultrastructure; D001921:Brain / Q000187:drug effects / Q000648:ultrastructure; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004983:Ethanolamines / Q000494:pharmacology*; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D006531:HEPES / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007381:Intermediate Filament Proteins / Q000032:analysis; D051379:Mice; D016900:Neurofilament Proteins; D009474:Neurons / Q000032:analysis / Q000187:drug effects* / Q000648:ultrastructure; D010879:Piperazines / Q000494:pharmacology*
D004983:Ethanolamines; D005904:Glial Fibrillary Acidic Protein; D007381:Intermediate Filament Proteins; D016900:Neurofilament Proteins; D010879:Piperazines; C009546:triethanolamine; D006861:Hydrogen Peroxide; D006531:HEPES