ABSTRACT
Progesterone (PROG), a steroid classically associated with reproductive functions, also provides neuroprotection to the lesioned peripheral and central nervous system, including the spinal cord. The latter is a target of PROG, as neurons and/or glial cells express intracellular receptors as well as membrane receptors for PROG. When spinal cord injury (SCI) is produced at the thoracic level, several genes become sensitive to PROG in the region caudal to the lesion site. Although the molecular mechanisms implicated in PROG neuroprotection remain elusive, several reports point to neurotrophic factors, their receptors and signaling cascades as possible intermediates of steroid action. Indeed, a 3-day course of PROG treatment to the injured animals increased the mRNA of brain-derived neurotrophic factor (BDNF) and BDNF immunoreactivity in perikaryon and processes of motoneurons, while neuronal chromatolytic changes were strongly prevented. Interestingly, previous data demonstrated that BDNF mimics some of these PROG effects in the spinal cord, suggesting that BDNF and PROG may share common intracellular pathways. Furthermore, PROG enhancement of endogenous BDNF may provide a local trophic support and regulate in a paracrine or autocrine fashion the function of neurons and glial cells to prevent cellular death after injury.