Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Crit Care Med. May 4, 2017; 6(2): 107-115
Published online May 4, 2017. doi: 10.5492/wjccm.v6.i2.107
Female gonadal hormone effects on microglial activation and functional outcomes in a mouse model of moderate traumatic brain injury
Odera Umeano, Haichen Wang, Hana Dawson, Beilei Lei, Afoma Umeano, Dawn Kernagis, Michael L James
Odera Umeano, School of Medicine, Duke University, Durham, NC 27710, United States
Haichen Wang, Hana Dawson, Department of Medicine, Division of Neurology, Duke University, Durham, NC 27710, United States
Beilei Lei, Michael L James, Multidisciplinary Neuroprotection Laboratories, Department of Anesthesiology, Duke University, Durham, NC 27710, United States
Afoma Umeano, Department of Chemistry, Harvard University, Cambridge, MA 27710, United States
Dawn Kernagis, Department of Anesthesiology, Duke University, Durham, NC 27710, United States
Author contributions: All authors contributed to this manuscript.
Institutional review board statement: This study was approved by the Duke University Animal Care and Use Committee.
Conflict-of-interest statement: All authors have no conflicts of interest to declare.
Data sharing statement: All data and all data are reposited at Duke University in Durham, NC.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Michael L James, Associate Professor of Anesthesiology and Neurology, Multidisciplinary Neuroprotection Laboratories, Department of Anesthesiology, Duke University, DUMC 3094, Durham, NC 27710, United States. michael.james@duke.edu
Telephone: +1-919-6816472 Fax: +1-919-6814698
Received: June 30, 2016
Peer-review started: July 1, 2016
First decision: August 5, 2016
Revised: December 20, 2016
Accepted: January 11, 2017
Article in press: January 11, 2017
Published online: May 4, 2017
Processing time: 306 Days and 7.3 Hours
Abstract
AIM

To address the hypothesis that young, gonad-intact female mice have improved long-term recovery associated with decreased neuroinflammation compared to male mice.

METHODS

Eight to ten week-old male, female, and ovariectomized (OVX) mice underwent closed cranial impact. Gonad-intact female mice were injured only in estrus state. After injury, between group differences were assessed using complementary immunohistochemical staining for microglial cells at 1 h, mRNA polymerase chain reaction for inflammatory markers at 1 h after injury, Rotarod over days 1-7, and water maze on days 28-31 after injury.

RESULTS

Male mice had a greater area of injury (P = 0.0063), F4/80-positive cells (P = 0.032), and up regulation of inflammatory genes compared to female mice. Male and OVX mice had higher mortality after injury when compared to female mice (P = 0.043). No group differences were demonstrated in Rotarod latencies (P = 0.62). OVX mice demonstrated decreased water maze latencies compared to other groups (P = 0.049).

CONCLUSION

Differences in mortality, long-term neurological recovery, and markers of neuroinflammation exist between female and male mice after moderate traumatic brain injury (MTBI). Unexpectedly, OVX mice have decreased long term neurological function after MTBI when compared to gonad intact male and female mice. As such, it can be concluded that the presence of female gonadal hormones may influence behavioural outcomes after MTBI, though mechanisms involved are unclear.

Keywords: Traumatic brain injury; Microglia; Functional recovery; Inflammation; Sex

Core tip: Differences in mortality, long-term neurological recovery, and markers of neuroinflammation exist between female and male mice after moderate traumatic brain injury (MTBI). Unexpectedly, ovariectomized mice have decreased long term neurological function after MTBI when compared to gonad intact male and female mice.