雌激素及雌激素类化合物在脊髓损伤中的神经保护作用。

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

作者信息

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

机构信息

Black Dog Institute, Sydney, Australia; School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, Australia.

School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, Australia.

出版信息

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

DOI:10.1016/j.neubiorev.2023.105074

PMID:36736846

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.

摘要

脊髓损伤（SCI）是指脊髓因创伤性事件或疾病而受损。SCI的特征是多个损伤阶段，这些阶段会影响感觉和运动信号的传递，并导致暂时或长期的功能缺陷。目前针对SCI的治疗方法很少。然而，雌激素和雌激素类化合物可能有效地减轻SCI的影响，因此是可行的治疗选择。本综述系统地研究了SCI后雌激素和雌激素类化合物神经保护作用的临床前文献。纳入研究的几种雌激素包括：雌激素、苯甲酸雌二醇、普雷马林、异补骨脂素、染料木黄酮和选择性雌激素受体调节剂。在这些药物治疗中，我们发现有充分证据表明雌激素确实能抵御SCI的多种病理生理效应，并改善包括运动能力在内的功能结局。对SCI后受雌激素调节的蛋白质进行的STRING功能网络分析表明，雌激素同时上调已知的神经保护途径，如低氧诱导因子-1（HIF-1），并下调促炎途径，包括白细胞介素-17（IL-17）。这些发现凸显了SCI后雌激素和雌激素类化合物强大的治疗潜力。