Effect of Progesterone on Cerebral Vasospasm and Neurobehavioral Outcomes in a Rodent Model of Subarachnoid Hemorrhage

Nefize Turan, Brandon A. Miller, J. Russell Huie, Robert A. Heider, Jun Wang, Bushra Wali, Seema Yousuf, Adam R. Ferguson, Iqbal Sayeed, Donald G. Stein, Gustavo Pradilla

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Background Subarachnoid hemorrhage (SAH) induces widespread inflammation leading to cellular injury, vasospasm, and ischemia. Evidence suggests that progesterone (PROG) can improve functional recovery in acute brain injury owing to its anti-inflammatory and neuroprotective properties, which could also be beneficial in SAH. We hypothesized that PROG treatment attenuates inflammation-mediated cerebral vasospasm and microglial activation, improves synaptic connectivity, and ameliorates functional recovery after SAH. Methods We investigated the effect of PROG in a cisternal SAH model in adult male C57BL/6 mice. Neurobehavioral outcomes were evaluated using rotarod latency and grip strength tests. Basilar artery perimeter, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptor 1 (GluR1)/synaptophysin colocalization, and Iba-1 immunoreactivity were quantified histologically. Results PROG (8 mg/kg) significantly improved rotarod latency at day 6 and grip strength at day 9. PROG-treated mice had significantly reduced basilar artery vasospasm at 24 hours. GluR1/synaptophysin colocalization, indicative of synaptic GluR1, was significantly reduced in the SAH+Vehicle group at 24 hours, and PROG treatment significantly attenuated this reduction. PROG treatment significantly reduced microglial cell activation and proliferation in cerebellum and cortex but not in the brainstem at 10 days. Conclusions PROG treatment ameliorated cerebral vasospasm, reduced microglial activation, restored synaptic GluR1 localization, and improved neurobehavioral performance in a murine model of SAH. These results provide a rationale for further translational testing of PROG therapy in SAH.

Original languageEnglish
Pages (from-to)e150-e159
JournalWorld Neurosurgery
StatePublished - Feb 2018

Bibliographical note

Funding Information:
Conflict of interest statement: This work was supported by Kristen's Legacy of Love Chair of Research (G.P.) and Karen M. Schurr Memorial Chair of Research (B.A.M.) Grants by the Brain Aneurysm Foundation, Emory Medical Care Foundation (G.P.), Emory University Department of Neurosurgery departmental funds (G.P.) and Emory University Integrated Cellular Imaging Microscopy Core. Along with Emory University, D.G.S. and I.S. hold several patents on the use of progesterone for traumatic brain injury but currently have no licensing, royalty, or payment agreements associated with this intellectual property.

Publisher Copyright:
© 2017 Elsevier Inc.

Copyright 2019 Elsevier B.V., All rights reserved.


  • Glutamate receptors
  • Microglia
  • Neurobehavioral tests
  • Progesterone
  • Subarachnoid hemorrhage
  • Vasospasm

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology


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