Development of therapies based on neuroactive steroids and neurosteroids for the treatment of experimental neuropathologies

Steroids showing activity on the nervous system are known as "neuroactive steroids". They exert neuroprotective or neurotoxic activities, depending on their chemical structure, circulating or tissue concentrations, binding to different receptors and the mechanisms of intracellular signalling employed. In order to elucidate these properties, work was performed on animal models of human neuropathologies, including spinal cord injury, neuropathic pain, multiple sclerosis, and amyotrophic lateral sclerosis. In these models, treatment with progesterone has shown great therapeutic effectiveness. In another set of studies, it was shown that hypertensive animals bear a pronounced encephalopathy, possibly caused by an overdrive of the mineralocorticoid system. It has been suggested that overdrive of the mineralocorticoid system plays a neurotoxic role, based on the development of similar brain abnormalities following mineralocorticoid treatment of otherwise normal animals. Hypertensive encephalopathy is similar to that developed by diabetes mellitus and aging animals. In the three cases, estrogen treatment provided strong neuroprotection, as shown by enhanced hippocampal neurogenesis, increased neurotrophic factor expression and decreased astrogliosis. Thus, the use of estrogens supports the regenerative capacity and plasticity of the nervous system. Therefore, animal models become useful tools to transfer experimental data to the human patient in the short-term.