Comorbidities like diabetes, hypertension, hypercholesterolemia, and aging worsen stroke outcomes. Diabetes and stroke both involve multiple inflammatory changes in the pancreas, spleen, thymus, blood, brain, and nerves, and both are associated with dysfunction in re-vascularization and inflammation-related pathways. Inflammation is a major driving force in diabetes complications. We recently completed work showing the beneficial effects of progesterone on diabetes/hyperglycemia-induced damage to the brain, spinal cord and sciatic nerve in male rats without stroke.
We are now testing the effects of progesterone in diabetic stroke in male and female animals. In this endeavor, we are collaborating with Drs. Machelle Pardue and Rachael Stewart, colleagues at the Atlanta VA. We are hoping that the successful completion of these studies will build a foundation for a clinical trial for progesterone in stroke. We are in the process of submitting several proposals to the NIH.
For 2019, we have several ongoing in vitro and in vivo studies. We are using an in vitro model of diabetic neuronal injury using mouse primary cortical neurons. We performed a dose-response curve using progesterone against diabetic neuronal injury and found that in vitro-induced diabetes exacerbated neuronal injury and progesterone reduced this effect significantly. In vivo, we are currently evaluating the effect of diabetes on behavioral and histological outcomes of TBI in adult male and female rats.
The next steps will include: testing progesterone in the treatment of diabetic TBI (short- and long-term); measuring sex differences in the outcomes of diabetic TBI and progesterone treatment; examining age-related differences in the outcomes of diabetic TBI and progesterone treatment; identifying some of the specific mechanisms of progesterone’s action in diabetic TBI. We expect to complete this series of experiments by the end of August 2019.