Traumatic brain injury and aging: is a combination of progesterone and vitamin D hormone a simple solution to a complex problem?

Although progress is being made in the development of new clinical treatments for traumatic brain injury (TBI), little is known about whether such treatments are effective in older patients, in whom frailty, prior medical conditions, altered metabolism, and changing sensitivity to medications all can affect outcomes following a brain injury. In this review we consider TBI to be a complex, highly variable, and systemic disorder that may require a new pharmacotherapeutic approach, one using combinations or cocktails of drugs to treat the many components of the injury cascade. We review some recent research on the role of vitamin D hormone and vitamin D deficiency in older subjects, and on the interactions of these factors with progesterone, the only treatment for TBI that has shown clinical effectiveness. Progesterone is now in phase III multicenter trial testing in the United States. We also discuss some of the potential mechanisms and pathways through which the combination of hormones may work, singly and in synergy, to enhance survival and recovery after TBI. Copyright 2010 The American Society for Experimental NeuroTherapeutics, Inc. Published by Elsevier Inc. All rights reserved.