At present, there is no effective pharmacological agent to enhance neurobehavioral recovery after traumatic brain injury (TBI). The long-term objective of this research is to develop a safe and effective treatment that would enhance neurorehabilitation after traumatic injuries to the central nervous system. After the initial cascade of destructive events occurs, the brain is in a state of dysfunction due to injured neurons, disrupted synapses, continuing inflammatory responses, and decreased neuronal activity. However, the brain has the capability to recover significantly from this post-injury state, if proper behavioral or pharmacological therapies are administered. In this proposal, it is the investigators'goal to demonstrate that dihydroepiandrosterone (DHEA) will significantly increase recovery of function. DHEA is a special type of steroid hormone that is synthesized both inside and outside of the nervous system in both males and females. DHEA, a known neurosteroid, can stimulate the formation of new synapses, modulate the immune system, and increase neuronal activity involved in cognitive function. These same characteristics make DHEA worth considering as potential therapy to facilitate recovery of cognitive function after brain injury. In addition, long-term administration of DHEA has shown that it produces no adverse side-effects in rodents or humans. In this proposal, the investigators will investigate whether DHEA can promote a more complete recovery of function after experimental TBI. The investigators will use a controlled cortical impactor to create bilateral medial frontal contusions in rats to model TBI. The investigators goals will be to: (1) determine whether DHEA can promote functional recovery in both males and females, a subject that has received virtually no attention in the experimental literature; (2) determine the most effective dose of DHEA; (3) determine whether treatment with DHEA can affect the morphology and survival of neurons as well as the proliferation of glial cells; and (4) determine if the effects of DHEA on recovery of function can produce a dose dependent causal effect on histological measures.
| Hoffman, Stuart W; Virmani, Sharad; Simkins, Robert M et al. (2003) The delayed administration of dehydroepiandrosterone sulfate improves recovery of function after traumatic brain injury in rats. J Neurotrauma 20:859-70 |
