The neuroprotective effects of estrogen and estrogenic compounds in spinal cord injury

Artur Shvetcov; Marc J Ruitenberg; Fabien Delerue; Wendy A Gold; David A Brown; Caitlin A Finney

doi:10.1016/j.neubiorev.2023.105074

The neuroprotective effects of estrogen and estrogenic compounds in spinal cord injury

Neurosci Biobehav Rev. 2023 Mar:146:105074. doi: 10.1016/j.neubiorev.2023.105074. Epub 2023 Feb 2.

Authors

Artur Shvetcov¹, Marc J Ruitenberg², Fabien Delerue³, Wendy A Gold⁴, David A Brown⁵, Caitlin A Finney⁶

Affiliations

¹ Black Dog Institute, Sydney, Australia; School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, Australia.
² School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, Australia.
³ Dementia Research Centre, Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, Australia.
⁴ School of Medical Sciences, Faculty of Medicine Health, The University of Sydney, Sydney, Australia; Molecular Neurobiology Research Laboratory, Kids Research, Children's Hospital at Westmead and the Children's Medical Research Institute, Westmead, Australia; Kids Neuroscience Centre, Kids Research, Children's Hospital at Westmead, Westmead, Australia.
⁵ Neuroinflammation Research Group, Centre for Immunology and Allergy Research, Westmead Institute for Medical Research, Sydney, Australia; Department of Immunopathology, Institute for Clinical Pathology and Medical Research-New South Wales Health Pathology, Westmead Hospital, Sydney, Australia; Westmead Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.
⁶ School of Medical Sciences, Faculty of Medicine Health, The University of Sydney, Sydney, Australia; Neuroinflammation Research Group, Centre for Immunology and Allergy Research, Westmead Institute for Medical Research, Sydney, Australia. Electronic address: caitlin.finney@wimr.org.au.

PMID: 36736846
DOI: 10.1016/j.neubiorev.2023.105074

Abstract

Spinal cord injury (SCI) occurs when the spinal cord is damaged from either a traumatic event or disease. SCI is characterised by multiple injury phases that affect the transmission of sensory and motor signals and lead to temporary or long-term functional deficits. There are few treatments for SCI. Estrogens and estrogenic compounds, however, may effectively mitigate the effects of SCI and therefore represent viable treatment options. This review systematically examines the pre-clinical literature on estrogen and estrogenic compound neuroprotection after SCI. Several estrogens were examined by the included studies: estrogen, estradiol benzoate, Premarin, isopsoralen, genistein, and selective estrogen receptor modulators. Across these pharmacotherapies, we find significant evidence that estrogens indeed offer protection against myriad pathophysiological effects of SCI and lead to improvements in functional outcomes, including locomotion. A STRING functional network analysis of proteins modulated by estrogen after SCI demonstrated that estrogen simultaneously upregulates known neuroprotective pathways, such as HIF-1, and downregulates pro-inflammatory pathways, including IL-17. These findings highlight the strong therapeutic potential of estrogen and estrogenic compounds after SCI.

Keywords: Estrogen; Estrogenic compounds; Neuroprotection; Spinal cord injury.

Publication types

Review

MeSH terms

Animals
Estrogens / metabolism
Humans
Neuroprotective Agents* / therapeutic use
Rats
Rats, Sprague-Dawley
Spinal Cord
Spinal Cord Injuries*

Substances

Estrogens
Neuroprotective Agents