Exogenous progesterone is neuroprotective following injury to the male zebra finch brain

Abstract

The use of progesterone following brain injury has a controversial history. On one hand, some lab-based models have showed progesterone as being neuroprotective, but on the other, clinical trials have showed quite the opposite. One of many complaints that arose from this discrepancy was the lack of a diverse pool of animal models and paradigms employed during the preclinical phase. However, over the past decade, the zebra finch has emerged as an optimal organism for the study of steroid-mediated neuroprotection. Following an injury, steroid hormones and receptors are upregulated, serving to decrease neuroinflammation and overall damage to the brain. As compared to other vertebrate models, zebra finches can upregulate expression of both estrogens and androgens at a faster and more robust response, suggesting that vertebrates differ in their neuroprotective mechanisms and timing following injury. Therefore, to expand the types organisms studied in pre-clinical trials, we chose to use zebra finches. While the majority of work in the zebra finch brain has focused on estrogens and androgens, we sought to clarify the role of progesterone following injury. Adult male zebra finches were given daily injections of progesterone following a penetrating injury and then were assessed for the size of injury and expression of various genes associated with neuroinflammation and cell survival. Treatment with progesterone decreased the injury size in zebra finches over controls and increased expression of various genes associated with cell survival and neuroinflammation. These data suggest that progesterone does mediate neuroprotection, most likely through the alteration of neuroinflammatory and cell survival pathways.