Role of thyroid hormones in different aspects of nervous system regeneration in vertebrates.

Spontaneous functional recovery from injury in the adult human nervous system is rare and trying to improve recovery remains a clinical challenge. Nervous system regeneration is a complicated sequence of events involving cell death or survival, cell proliferation, axon extension and remyelination, and finally reinnervation and functional recovery. Successful recovery depends on the cell-specific and time-dependent activation and repression of a wide variety of growth factors and guidance molecules. Thyroid hormones (THs), well known for their regulatory role in neurodevelopment, have recently emerged as important modulators of neuroregeneration. This review focuses on the endogenous changes in the proteins regulating TH availability and action in different cell types of the adult mammalian nervous system during regeneration as well as the impact of TH supplementation on the consecutive steps in this process. It also addresses possible differences in TH involvement between different vertebrate classes, early or late developmental stages and peripheral or central nervous system. The available data show that THs are able to stimulate many signaling pathways necessary for successful neurogeneration. They however also suggest that supplementation with T4 and/or T3 may have beneficial or detrimental influences depending on the dose and more importantly on the specific phase of the regeneration process.