Towards brain repair: Insights from teleost fish.

In the adult mammalian brain, the ability to minimize secondary cell death after injury, and to repair nervous tissue through generation of new neurons, is severely compromised. By contrast, certain taxa of non-mammalian vertebrates possess an enormous potential for regeneration. Examination of one of these taxa, teleost fish, has revealed a close link between this phenomenon and constitutive adult neurogenesis. Key factors mediating successful regeneration appear to be: elimination of damaged cells by apoptosis, instead of necrosis; activation of mechanisms that prevent the occurrence of secondary cell death; increased production of new neurons that replace neurons lost to injury; and activation of developmental mechanisms that mediate directed migration of the new cells to the site of injury, the differentiation of the young cells, and their integration into the existing neural network. Comparative analysis has suggested that constitutive adult neurogenesis is a primitive vertebrate trait, the main function of which has been to ensure a numerical matching between muscle fibers/sensory receptor cells and central elements involved in motor control/processing of sensory information associated with these peripheral elements. It is hypothesized that, when in the course of the evolution of mammals a major shift in the growth pattern from hyperplasia to hypertrophy took place, the number of neurogenic brain regions and new neurons markedly decreased. As a consequence, the potential for neuronal regeneration was greatly reduced, but remnants of neurogenic areas have persisted in the adult mammalian brain in form of quiescent stem cells. It is likely that the study of regeneration-competent taxa will provide important information on how to activate intrinsic mechanisms for successful brain regeneration in humans.