Studies on the neuroprotective and promyelinating effects of progesterone in the 
nervous system are of great interest due to their potential clinical 
connotations. In peripheral neuropathies, progesterone and reduced derivatives 
promote remyelination, axonal regeneration and the recovery of function. In 
traumatic brain injury (TBI), progesterone has the ability to reduce edema and 
inflammatory cytokines, prevent neuronal loss and improve functional outcomes. 
Clinical trials have shown that short-and long-term progesterone treatment 
induces a significant improvement in the level of disability among patients with 
brain injury. In experimental spinal cord injury (SCI), molecular markers of 
functional motoneurons become impaired, including brain-derived neurotrophic 
factor (BDNF) mRNA, Na,K-ATPase mRNA, microtubule-associated protein 2 and 
choline acetyltransferase (ChAT). SCI also produces motoneuron chromatolysis. 
Progesterone treatment restores the expression of these molecules while 
chromatolysis subsided. SCI also causes oligodendrocyte loss and demyelination. 
In this case, a short progesterone treatment enhances proliferation and 
differentiation of oligodendrocyte progenitors into mature myelin-producing 
cells, whereas prolonged treatment increases a transcription factor (Olig1) 
needed to repair injury-induced demyelination. Progesterone neuroprotection has 
also been shown in motoneuron neurodegeneration. In Wobbler mice spinal cord, 
progesterone reverses the impaired expression of BDNF, ChAT and Na,K-ATPase, 
prevents vacuolar motoneuron degeneration and the development of mitochondrial 
abnormalities, while functionally increases muscle strength and the survival of 
Wobbler mice. Multiple mechanisms contribute to these progesterone effects, and 
the role played by classical nuclear receptors, extra nuclear receptors, 
membrane receptors, and the reduced metabolites of progesterone in 
neuroprotection and myelin formation remain an exciting field worth of 
exploration.