Progesterone in the Experimental Treatment of Central and Peripheral Nervous System Injuries

Although traumatic brain injury (TBI) is a serious medical problem, no clinically effective acute-stage treatments exist. Over the last few decades, dozens of pharmacological agents have been tested and many appeared to work well in animal models of TBI, but then failed in clinical trials. These agents were often designed to work on a specific molecular target – a receptor mechanism or an excitatory or inhibitory neurotransmitter – but when administered to patients with brain trauma, they performed no better than placebos or had substantially negative side effects. Recently, laboratory and clinical investigators have been examining the role of neurosteroids in the treatment of TBI, ischemic stroke and certain peripheral nervous system disorders. Progesterone and its metabolite allopregnanolone act on a number of molecular and physiological processes in the cascade of cellular damage that follows a TBI, ischemic attack or peripheral nerve crush injury. This paper reviews the literature showing that progesterone and allopregnanolone may hold considerable promise for the safe and effective treatment of TBI and stroke patients.