Abstract 14: Estrone Is Neuroprotective in Rats Following Traumatic Brain Injury
Introduction: In various animal and human studies, early administration of 17 beta-estradiol, a strong anti-oxidant, anti-inflammatory, and anti-apoptotic agent significantly decreases the severity of injury in the brain caused by early, devastating cell death. With respect to estrone (predominant estrogen in postmenopausal women), this estrogen has shown to be extremely promising as a neuro-protective agent. For example, in rats following stroke, estrone treatment resulted in a significant decrease in lesion volume after reperfusion injury. The overall goal of this project is to determine if estrone mitigates secondary injury following TBI in rats. Here, we hypothesized that estrone is neuro-protective following TBI.
Methods: In this study, 6 male rats were treated with either placebo (corn oil; n=3) or estrone (0.5mg/kg; n=3) at 30 minutes after severe TBI. In brief, using the controlled cortical impact device in rats that underwent a craniotomy, the right parietal cortex was injured using the impactor tip. Non-injured (n=3) and sham (craniotomy only; n=3) were also included in this study. At 72 hours following injury, the animals were intracardially perfused with 0.9% saline followed by 10% phosphate-buffered formalin. The whole brain was removed, sliced, and stained for active caspase-3 and TUNEL + cells. To test the efficacy of estrone in combating oxidant injury and ischemia, we also treated primary cortical neurons with tert-butyl hydrogen peroxide (100 micro-molar) and iodoacetic acid (IAA;10 micro-molar), respectively. Estrone (10 micro-molar) was added to the cells 15 minutes post-injury.
Results: Estrone significantly decreased the levels of cell death in primary cortical neurons treated with IAA (p<0.00002) and tert-butyl Hydrogen peroxide (p<0.001) at the 24 hour time-point. In addition, the TBI rats treated with estrone had reduced cortical and hippocampal levels of active caspase-3 (~24%) and TUNEL + staining (~18%).
Conclusion: Estrone given acutely after injury results in a decrease in ischemic secondary injury, oxidant injury, and apoptotic-mediated cell death. These results suggest that other estrogens in addition to estradiol may afford individuals protection suffering TBI.
- © 2011 by American Heart Association, Inc.