Sex steroid hormones as neuroprotective elements in ischemia models

Abstract

Among sex steroid hormones, progesterone and estradiol have a wide diversity of physiological activities that target the nervous system. Not only are they carried by the blood stream, but also they are locally synthesized in the brain and for this reason, estradiol and progesterone are considered 'neurosteroids'. The physiological actions of both hormones range from brain development and neurotransmission to aging, illustrating the importance of a deep understanding of their mechanisms of action. In this review, we summarize key roles that estradiol and progesterone play in the brain. As numerous reports have confirmed a substantial neuroprotective role for estradiol in models of neurodegenerative disease, we focus this review on traumatic brain injury and stroke models. We describe updated data from receptor and signaling events triggered by both hormones, with an emphasis on the mechanisms that have been reported as 'rapid' or 'cytoplasmic actions'. Data showing the therapeutic effects of the hormones, used alone or in combination, are also summarized, with a focus on rodent models of middle cerebral artery occlusion (MCAO). Finally, we draw attention to evidence that neuroprotection by both hormones might be due to a combination of 'cytoplasmic' and 'nuclear' signaling.

Molecular mechanisms and cellular events involved in the neuroprotective actions of estradiol. Analysis of sex differences

“…Liu et al, 2011S.B. Liu et al, , 2012Céspedes Rubio et al, 2018). For instance, G1 and the non-classical ER ligand STX protect against hippocampal neuronal loss induced by ischemia in middle-aged female rats (Lebesque et al, 2010).…”

“…Recent papers have reviewed the neuroprotective actions of sex hormones and related synthetic steroids in different central nervous system (CNS) pathologies (Elkabes and Nicot, 2014;Engler-Chiurazzi et al, 2017: Baez-Jurado et al, 2018Céspedes Rubio et al, 2018;Bourque et al, 2019;Kulkarni et al, 2019;Sohrabji et al, 2019), including some of the specific molecular neuroprotective mechanisms activated by estradiol (Arevalo et al, 2015;Sohrabji, 2015;Labandeira-Garcia et al, 2016;Zup and Madden, 2016;Marin and Diaz, 2018;Thakkar et al, 2018) and the role played by glial cells on the neuroprotective mechanisms of the hormone (Karki et al, 2014;Acaz-Fonseca et al, 2016;Kipp et al, 2016;Martin-Jimenez et al, 2019). Another important issue that has been considered in recent years is the neuroprotective role of estradiol locally synthesized in the CNS (Pedersen et al, 2018;Brocca and Garcia-Segura, 2018).…”

Pregnancies alters spine number in cortical and subcortical limbic brain regions of old rats

“…It is well demonstrated that E2 has neuroprotective properties (for review see Céspedes‐Rubio, Pérez‐Alvarez, Lapuente Chala, & Wandosell, ; Zárate et al, ). This effect of estrogens arises from various epidemiological studies, which showed that the survival of women is greater than that of men (for review see Kua et al, ).…”

“…This effect of estrogens arises from various epidemiological studies, which showed that the survival of women is greater than that of men (for review see Kua et al, ). In addition, neuropathological studies have shown that E2 protects women from several neurological diseases such as Parkinsonʾs disease (PD) and strokes (for review see Céspedes‐Rubio et al, ; Flores, Flores‐Gómez, et al, ). However, there are no reports showing that pregnancy has a neuroprotective effect on aging or on neuronal communication.…”

Progesterone Effects in the Nervous System

“…In mice, progesterone protects hippocampal structures as well as memory functions, which might reduce neurocognitive limitations for patients with brain tumors after exposure (Yousuf et al, ). Additionally, diverse ischemia models in rodents encourage the neuroprotective quality of progesterone (Céspedes Rubio et al, ). Here, after progesterone application and activation of PR, the density of different neural cell types and oligodendroglial cells was increased; meanwhile, the number of activated astrocytes was decreased (Zhu et al, ).…”