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Progesterone Improves Neurobehavioral Outcome in Models of Intracerebral Hemorrhage.

Publication ,  Conference
Lei, B; Wang, H; Jeong, S; Hsieh, JT; Majeed, M; Dawson, H; Sheng, H; Warner, DS; James, ML
Published in: Neuroendocrinology
2016

In models of acute brain injury, progesterone improves recovery through several mechanisms including modulation of neuroinflammation. Secondary injury from neuroinflammation is a potential therapeutic target after intracerebral hemorrhage (ICH). For potential translation of progesterone as a clinical acute ICH therapeutic, the present study sought to define efficacy of exogenous progesterone administration in ICH-relevant experimental paradigms. Young and aged C57BL/6 male, female, and ovariectomized (OVX) mice underwent left intrastriatal collagenase (0.05-0.075 U) or autologous whole blood (35 μl) injection. Progesterone at varying doses (4-16 mg/kg) was administered at 2, 5, 24, 48, and 72 h after injury. Rotarod and Morris water maze latencies were measured on days 1-7 and days 28-31 after injury, respectively. Hematoma volume, brain water content (cerebral edema), complementary immunohistochemistry, multiplex cytokine arrays, and inflammatory proteins were assessed at prespecified time points after injury. Progesterone (4 mg/kg) administration improved rotarod and water maze latencies (p < 0.01), and decreased cerebral edema (p < 0.05), microglial proliferation, and neuronal loss (p < 0.01) in young and aged male, young OVX, and aged female mice. Brain concentration of proinflammatory cytokines and Toll-like receptor-associated proteins were also decreased after progesterone (4 mg/kg) treatment (p < 0.01). Progesterone-treated young female mice showed no detectable effects. Exogenous progesterone improved short- and long-term neurobehavioral recovery and modulated neuroinflammation in male and OVX mice after ICH. Future studies should validate these findings, and address timing and length of administration before translation to clinical trial.

Duke Scholars

Published In

Neuroendocrinology

DOI

EISSN

1423-0194

Publication Date

2016

Volume

103

Issue

6

Start / End Page

665 / 677

Location

Switzerland

Related Subject Headings

  • Treatment Outcome
  • Toll-Like Receptors
  • Progestins
  • Progesterone
  • Ovariectomy
  • Mice, Inbred C57BL
  • Mice
  • Maze Learning
  • Male
  • Hematoma
 

Citation

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Chicago
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MLA
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Lei, B., Wang, H., Jeong, S., Hsieh, J. T., Majeed, M., Dawson, H., … James, M. L. (2016). Progesterone Improves Neurobehavioral Outcome in Models of Intracerebral Hemorrhage. In Neuroendocrinology (Vol. 103, pp. 665–677). Switzerland. https://doi.org/10.1159/000442204
Lei, Beilei, Haichen Wang, Seongtae Jeong, Justin T. Hsieh, Mohammed Majeed, Hana Dawson, Huaxin Sheng, David S. Warner, and Michael L. James. “Progesterone Improves Neurobehavioral Outcome in Models of Intracerebral Hemorrhage.” In Neuroendocrinology, 103:665–77, 2016. https://doi.org/10.1159/000442204.
Lei B, Wang H, Jeong S, Hsieh JT, Majeed M, Dawson H, et al. Progesterone Improves Neurobehavioral Outcome in Models of Intracerebral Hemorrhage. In: Neuroendocrinology. 2016. p. 665–77.
Lei, Beilei, et al. “Progesterone Improves Neurobehavioral Outcome in Models of Intracerebral Hemorrhage.Neuroendocrinology, vol. 103, no. 6, 2016, pp. 665–77. Pubmed, doi:10.1159/000442204.
Lei B, Wang H, Jeong S, Hsieh JT, Majeed M, Dawson H, Sheng H, Warner DS, James ML. Progesterone Improves Neurobehavioral Outcome in Models of Intracerebral Hemorrhage. Neuroendocrinology. 2016. p. 665–677.
Journal cover image

Published In

Neuroendocrinology

DOI

EISSN

1423-0194

Publication Date

2016

Volume

103

Issue

6

Start / End Page

665 / 677

Location

Switzerland

Related Subject Headings

  • Treatment Outcome
  • Toll-Like Receptors
  • Progestins
  • Progesterone
  • Ovariectomy
  • Mice, Inbred C57BL
  • Mice
  • Maze Learning
  • Male
  • Hematoma