Abstract W P257: Progesterone Improves Long-term Neurobehavioral Outcome in Models of Intracerebral Hemorrhage (ICH)
Introduction: Progesterone is known to improve recovery in traumatic and ischemic brain injury models. For potential translation, the present study sought to define efficacy of exogenous progesterone administration in murine models of ICH.
Methods: Young and aged C57/Bl6 male, female, and ovariectomized (OVX) mice underwent left intrastriatal collagenase (0.075U) or autologous whole blood (35ul) injection. Mice were randomized to receive progesterone at pre-specified doses (4-16 mg/kg), administered SQ at 2 and 5 hours after injury and then daily for 3 days. Rotorod (RR) and water maze (WM) latencies were measured by blinded observers on Days 1-7 and Days 28-31 after injury, respectively. Hematoma volume, brain water content, stereology of complementary immunohistochemistry, and multiplex cytokine arrays were measured at pre-specified time points after injury.
Results: Progesterone (4mg/kg) administration after injury increased RR and decrease WM latencies (See Figure), decreased cerebral edema (p=0.03), and decreased microglial proliferation and activation in young and aged male and OVX, but not female mice, while maintaining stable hematoma volumes. Progesterone (4mg/kg) administration also increased RR latencies and decreased cerebral edema in male mice after autologous blood injection. In male mice only, progesterone (4mg/kg) reduced brain IL6, TNF-α and KC/GRO production in multiplex cytokine measurement after injury.
Conclusions: Progesterone improves neurobehavioral recovery in male and OVX, but not gonad-intact female, mice by modulating neuroinflammation after ICH. Future study should address timing and length of administration prior to translation to clinical trial.
Author Disclosures: M.L. James: None. B. Lei: None. H. Sheng: None. H. Dawson: None. S. Jeong: None. J. Hsieh: None. D.T. Laskowitz: None. D.S. Warner: None.
- © 2015 by American Heart Association, Inc.