Comparative analysis of gonadal steroid-mediated neuroprotection after transient focal ischemia in rats: route of application and substrate composition.

Progesterone (P) and 17ß-estradiol (E2) mitigate neuronal damage after experimentally induced traumatic brain injury (TBI) and ischemic stroke. Fish oil components such as omega-3 polyunsaturated fatty acids (PUFA n3) also provide neuroprotection in these traumatic models. Steroids and PUFA n3 dampen neuroinflammatory processes and regulate glial function in the affected brain areas. Using a transient focal ischemic rat model, we demonstrate that the co-application of PUFA n3 and P/E2 and the choice of the application route have a clear impact on the prevention of ischemia-induced infarct volume and behavioral recovery. A combinatory PUFA n3 plus P/E2 emulsion intravenously administered was most effective in reducing the infarct size and in restoring behavioral reconstitution compared to other oil emulsions and subcutaneous depot medication. These data encourage to refining clinical treatment protocols for TBI and stroke with gonadal steroids and to establishing combinatory drugs of steroids and fish oil-enriched emulsions thereby creating a win-win situation with two effective components.