Molecular mechanisms of estrogen for neuroprotection in spinal cord injury and traumatic brain injury

Estrogen (EST) is a steroid hormone that exhibits several important physiological roles in the human body. During the last few decades, EST has been well recognized as an important neuroprotective agent in a variety of neurological disorders in the central nervous system (CNS), such as spinal cord injury (SCI), traumatic brain injury (TBI), Alzheimer’s disease, and multiple sclerosis. The exact molecular mechanisms of EST-mediated neuroprotection in the CNS remain unclear due to heterogeneity of cell populations that express EST receptors (ERs) in the CNS as well as in the innate and adaptive immune system. Recent investigations suggest that EST protects the CNS from injury by suppressing pro-inflammatory pathways, oxidative stress, and cell death, while promoting neurogenesis, angiogenesis, and neurotrophic support. In this review, we have described the currently known molecular mechanisms of EST-mediated neuroprotection and neuroregeneration in SCI and TBI. At the same time, we have emphasized on the recent in vitro and in vivo findings from our and other laboratories, implying potential clinical benefits of EST in the treatment of SCI and TBI.