Considerations for Studying Sex as a Biological Variable in Spinal Cord Injury

Andrew N. Stewart, Steven M. MacLean, Arnold J. Stromberg, Jessica P. Whelan, William M. Bailey, John C. Gensel, Melinda E. Wilson

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


In response to NIH initiatives to investigate sex as a biological variable in preclinical animal studies, researchers have increased their focus on male and female differences in neurotrauma. Inclusion of both sexes when modeling neurotrauma is leading to the identification of novel areas for therapeutic and scientific exploitation. Here, we review the organizational and activational effects of sex hormones on recovery from injury and how these changes impact the long-term health of spinal cord injury (SCI) patients. When determining how sex affects SCI it remains imperative to expand outcomes beyond locomotor recovery and consider other complications plaguing the quality of life of patients with SCI. Interestingly, the SCI field predominately utilizes female rodents for basic science research which contrasts most other male-biased research fields. We discuss the unique caveats this creates to the translatability of preclinical research in the SCI field. We also review current clinical and preclinical data examining sex as biological variable in SCI. Further, we report how technical considerations such as housing, size, care management, and age, confound the interpretation of sex-specific effects in animal studies of SCI. We have uncovered novel findings regarding how age differentially affects mortality and injury-induced anemia in males and females after SCI, and further identified estrus cycle dysfunction in mice after injury. Emerging concepts underlying sexually dimorphic responses to therapy are also discussed. Through a combination of literature review and primary research observations we present a practical guide for considering and incorporating sex as biological variable in preclinical neurotrauma studies.

Original languageEnglish
Article number802
JournalFrontiers in Neurology
StatePublished - Aug 5 2020

Bibliographical note

Funding Information:
Technical support for determining plasma estradiol concentrations was provided by the University of Virginia's Center for Research in Reproduction Ligand Assay and Analysis Core Supported by the Eunice Kennedy Shriver NICHD Grant R24 HD102061. Funding. This funding was supported by The National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health (NIH) under Awards: R01NS091582 and F32NS111241.

Publisher Copyright:
© Copyright © 2020 Stewart, MacLean, Stromberg, Whelan, Bailey, Gensel and Wilson.


  • bladder
  • estrogen
  • gender
  • pain
  • stroke
  • testosterone
  • traumatic brain injury (TBI)

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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