Astrocytes Mediate Protective Actions of Estrogenic Compounds after Traumatic Brain Injury

Martin-Jimenez, Cynthia; Gaitán-Vaca, Diana Milena; Areiza, Natalia; Echeverrı́a, Valentina; Ashraf, Ghulam Md; González, Janneth; Sahebkar, Amirhossein; García‐Segura, Luis M.; Barreto, George E.

doi:10.1159/000495078

Cited by 37 publications

(30 citation statements)

References 261 publications

(265 reference statements)

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“…Astrocytes participate in the protective actions of estrogenic compounds [110]. Recent findings point to the role of these inflammatory cells in mediating the effect of sex hormones on cognition.…”

Section: Neuroinflammationmentioning

confidence: 99%

Parkinson’s Disease in Women and Men: What’s the Difference?

Cerri¹,

Mus²,

Blandini³

2019

Journal of Parkinson’s Disease

484

309

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Increasing evidence points to biological sex as an important factor in the development and phenotypical expression of Parkinson's disease (PD). Risk of developing PD is twice as high in men than women, but women have a higher mortality rate and faster progression of the disease. Moreover, motor and nonmotor symptoms, response to treatments and disease risk factors differ between women and men. Altogether, sex-related differences in PD support the idea that disease development might involve distinct pathogenic mechanisms (or the same mechanism but in a different way) in male and female patients. This review summarizes the most recent knowledge concerning differences between women and men in PD clinical features, risk factors, response to treatments and mechanisms underlying the disease pathophysiology. Unraveling how the pathology differently affect the two sexes might allow the development of tailored interventions and the design of innovative programs that meet the distinct needs of men and women, improving patient care.

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Section: Neuroinflammationmentioning

confidence: 99%

Parkinson’s Disease in Women and Men: What’s the Difference?

Cerri¹,

Mus²,

Blandini³

2019

Journal of Parkinson’s Disease

484

309

View full text Add to dashboard Cite

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“…In recent years, several research groups demonstrated the effect of E2 as a possible therapeutic agent of TBI [19][20][21][22]. Accordingly, the aim of this review is to summarize the role and mechanism of action of E2 in TBI.…”

Section: Introductionmentioning

confidence: 99%

The Role of Estradiol in Traumatic Brain Injury: Mechanism and Treatment Potential

Kövesdi

Szabó-Meleg

Ábrahám

2020

IJMS

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Patients surviving traumatic brain injury (TBI) face numerous neurological and neuropsychological problems significantly affecting their quality of life. Extensive studies over the past decades have investigated pharmacological treatment options in different animal models, targeting various pathological consequences of TBI. Sex and gender are known to influence the outcome of TBI in animal models and in patients, respectively. Apart from its well-known effects on reproduction, 17β-estradiol (E2) has a neuroprotective role in brain injury. Hence, in this review, we focus on the effect of E2 in TBI in humans and animals. First, we discuss the clinical classification and pathomechanism of TBI, the research in animal models, and the neuroprotective role of E2. Based on the results of animal studies and clinical trials, we discuss possible E2 targets from early to late events in the pathomechanism of TBI, including neuroinflammation and possible disturbances of the endocrine system. Finally, the potential relevance of selective estrogenic compounds in the treatment of TBI will be discussed.

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“…The direct actions of tibolone on astrocytes and astrocyte-like cells through ERs, together with the decreased neuronal loss in association with a reduction of reactive astrogliosis in the injured cortex of tibolone-treated mice [16], suggest that astrocytes may be involved in the neuroprotective actions of the steroid. Indeed, it is known that astrocytes mediate the neuroprotective actions of estradiol and other ER ligands in different CNS (central nervous system) pathologies [20,21].…”

Section: Introductionmentioning

confidence: 99%

The synthetic steroid tibolone exerts sex-specific regulation of astrocyte phagocytosis under basal conditions and after an inflammatory challenge

Crespo‐Castrillo

Garcia-Segura

Arévalo

2020

J Neuroinflammation

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Background: Tibolone is a synthetic steroid used in clinical practice for the treatment of climacteric symptoms and osteoporosis. Active metabolites of tibolone, generated in target tissues, have an affinity for estrogen and androgen receptors. Astrocytes are direct targets for estrogenic compounds and previous studies have shown that tibolone protects brain cortical neurons in association with a reduction in reactive astrogliosis in a mouse model of traumatic brain injury. Since phagocytosis is a crucial component of the neuroprotective function exerted by astrocytes, in the present study, we have assessed whether tibolone regulates phagocytosis in primary astrocytes incubated with brain-derived cellular debris. Methods: Male and female astrocyte cell cultures were obtained from newborn (P0-P2) female and male Wistar rats. Astrocytic phagocytosis was first characterized using carboxylate beads, Escherichia coli particles, or brain-derived cellular debris. Then, the effect of tibolone on the phagocytosis of Cy3-conjugated cellular debris was quantified by measuring the intensity of Cy3 dye-emitted fluorescence in a given GFAP immunoreactive area. Before the phagocytosis assays, astrocytes were incubated with tibolone in the presence or absence of estrogen or androgen receptor antagonists or an inhibitor of the enzyme that synthesizes estradiol. The effect of tibolone on phagocytosis was analyzed under basal conditions and after inflammatory stimulation with lipopolysaccharide. Results: Tibolone stimulated phagocytosis of brain-derived cellular debris by male and female astrocytes, with the effect being more pronounced in females. The effect of tibolone in female astrocytes was blocked by a selective estrogen receptor β antagonist and by an androgen receptor antagonist. None of these antagonists affected tibolone-induced phagocytosis in male astrocytes. In addition, the inhibition of estradiol synthesis in the cultures enhanced the stimulatory effect of tibolone on phagocytosis in male astrocytes but blocked the effect of the steroid in female cells under basal conditions. However, after inflammatory stimulation, the inhibition of estradiol synthesis highly potentiated the stimulation of phagocytosis by tibolone, particularly in female astrocytes. Conclusions: Tibolone exerts sex-specific regulation of phagocytosis in astrocytes of both sexes, both under basal conditions and after inflammatory stimulation.

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Astrocytes Mediate Protective Actions of Estrogenic Compounds after Traumatic Brain Injury

Cited by 37 publications

References 261 publications

Parkinson’s Disease in Women and Men: What’s the Difference?

Parkinson’s Disease in Women and Men: What’s the Difference?

The Role of Estradiol in Traumatic Brain Injury: Mechanism and Treatment Potential

The synthetic steroid tibolone exerts sex-specific regulation of astrocyte phagocytosis under basal conditions and after an inflammatory challenge

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