Gonadal hormones down-regulate reactive gliosis and astrocyte proliferation after a penetrating brain injury

Garcı́a-Estrada, Joaquı́n; Río, José Antonio del; Luquı́n, Sonia; Soriano, Eduardo; Garcia-Segura, Luis Miguel

doi:10.1016/0006-8993(93)90964-o

Cited by 215 publications

(134 citation statements)

References 61 publications

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“…31,50 We found a significant dose-dependent reduction in GFAP-IR staining in both cortex and hippocampus in treatment groups that received E2, similar to previously reported findings. [51][52][53][54] In addition, protein expression levels of GFAP in the ipsilateral cortex following TBI induction were significantly increased; this was attenuated by G-1…”

Section: E2 or G-1 Increases Cell Survival Decreases Neuronal Degenementioning

confidence: 93%

17β-Estradiol Confers Protection after Traumatic Brain Injury in the Rat and Involves Activation of G Protein-Coupled Estrogen Receptor 1

Day

Floyd

D'Alessandro

et al. 2013

Journal of Neurotrauma

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Traumatic brain injury (TBI) is a significant public health problem in the United States. Despite preclinical success of various drugs, to date all clinical trials investigating potential therapeutics have failed. Recently, sex steroid hormones have sparked interest as possible neuroprotective agents after traumatic injury. One of these is 17b-estradiol (E2), the most abundant and potent endogenous vertebrate estrogen. The goal of our study was to investigate the acute potential protective effects of E2 or the specific G protein-coupled estrogen receptor 1 (GPER) agonist G-1 when administered in an intravenous bolus dose 1 hour post-injury in the lateral fluid percussion (LFP) rodent model of TBI. The results of this study show that, when assessed at 24 hours post-injury, E2 or G-1 confers protection in adult male rats subjected to LFP brain injury. Specifically, we found that an acute bolus dose of E2 or G-1 administered intravenously 1 hour post-TBI significantly increases neuronal survival in the ipsilateral CA 2/3 region of the hippocampus and decreases neuronal degeneration and apoptotic cell death in both the ipsilateral cortex and CA 2/3 region of the hippocampus. We also report a significant reduction in astrogliosis in the ipsilateral cortex, hilus, and CA 2/3 region of the hippocampus. Finally, these effects were observed to be chiefly dose-dependent for E2, with the 5 mg/kg dose generating a more robust level of protection. Our findings further elucidate estrogenic compounds as a clinically relevant pharmacotherapeutic strategy for treatment of secondary injury following TBI, and intriguingly, reveal a novel potential therapeutic target in GPER.

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Section: E2 or G-1 Increases Cell Survival Decreases Neuronal Degenementioning

confidence: 93%

17β-Estradiol Confers Protection after Traumatic Brain Injury in the Rat and Involves Activation of G Protein-Coupled Estrogen Receptor 1

Day

Floyd

D'Alessandro

et al. 2013

Journal of Neurotrauma

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“…In experimental models of injury, such as the traumatic brain injury (TBI) model, PROG treatment reduces edema, accumulation of astrocytes in the cortex, nuclear factor kappa B (NFkB) p65, active C3 fragments, IL1b, and TNF-a (Garcia-Estrada et al 1993, Grossman et al 2004, He et al 2004, Pettus et al 2005, Feeser & Loria 2011. Moreover, it attenuates the reaction of astrocytes and microglial/macrophage cells in spinal cord injury models (Garay et al 2011, Labombarda et al 2011 and decreases the lesion volume and the expression of IL1b, inducible nitric oxide synthase (iNOS; Gibson et al 2008), ionized calcium-binding adapter molecule 1 (Iba1), and cyclooxygenase-2 in ischemic stroke models (Jiang et al 2011).…”

Section: Neuroactive Steroids As Neuroinflammatory Modulatorsmentioning

confidence: 99%

“…Moreover, it attenuates the reaction of astrocytes and microglial/macrophage cells in spinal cord injury models (Garay et al 2011, Labombarda et al 2011 and decreases the lesion volume and the expression of IL1b, inducible nitric oxide synthase (iNOS; Gibson et al 2008), ionized calcium-binding adapter molecule 1 (Iba1), and cyclooxygenase-2 in ischemic stroke models (Jiang et al 2011). Also, testosterone treatment in TBI decreases vimentin, MHCII, and GFAP immunoreactive cells (Garcia-Estrada et al 1993, Barreto et al 2007) and after middle cerebral artery occlusion decreases GFAP immunostaining and astrocyte hypertrophy around the infarcted area (Pan et al 2005). All these data underline the ability of neuroactive steroids to positively influence the inflammatory events in different neurodegenerative conditions by suppressing the pro-inflammatory and emphasizing the anti-inflammatory response.…”

Section: Neuroactive Steroids As Neuroinflammatory Modulatorsmentioning

confidence: 99%

Neuroactive steroids, their metabolites, and neuroinflammation

Giatti¹,

Boraso²,

Melcangi³

et al. 2012

Journal of Molecular Endocrinology

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Neuroinflammation represents a common feature of many neurodegenerative diseases implicated both in their onset and progression. Neuroactive steroids act as physiological regulators and protective agents in the nervous system. Therefore, the attention of biomedical research has been recently addressed in evaluating whether neuroactive steroids, such as progestagens, androgens, and estrogens may also affect neuroinflammatory pathways. Observations so far obtained suggest a general anti-inflammatory effect with a beneficial relapse on several neurodegenerative experimental models, thus confirming the potentiality of a neuroprotective strategy based on neuroactive steroids. In this scenario, neuroactive steroid metabolism and the sophisticated machinery involved in their signaling are becoming especially attractive. In particular, because metabolism of neuroactive steroids as well as expression of their receptors is affected during the course of neurodegenerative events, a crucial role of progesterone and testosterone metabolites in modulating neuroinflammation and neurodegeneration may be proposed. In the present review, we will address this issue, providing evidence supporting the hypothesis that the efficacy of neuroactive steroids could be improved through the use of their metabolites.

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“…It is also important in maintenance of synaptic density and plasticity in the CA1 region of the hippocampus (HIPP), an area important to memory [3,4], and can facilitate synaptic plasticity of dendritic spines in the CA1 region of the HIPP [5,6]. It can also alter firing rates in neuronal communication in key areas of the brain like the hypothalamus [7], alter membrane receptor expression [8] and modulate reactivity of supportive neuronal cells such as astroglia [9]. Estrogen has also been found to enhance verbal memory and maintain the ability to learn new material.…”

Section: Estrogen and The Brainmentioning

confidence: 99%

Estrogen and schizophrenia in women: animal models lend a hand in understanding cognition

Belgrave¹,

Pato²,

Pato³

2017

IJCNMH

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Women experience a differential onset of schizophrenia symptoms and a bi-modal peak of onset in the early years of adulthood and in the post-menopausal period. Cognitive deficits that accompany schizophrenia are some of the more severe symptoms associated with the disease. The understanding of the mechanisms underlying cognitive dysfunction is still very limited and its understanding can bring important contributions to the adequate clinical management of the disease. Using rodent research to explore cognition, and how female hormones may affect cognitive decline with age in the context of schizophrenia can expand our understanding and perhaps offer more treatment options.

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Gonadal hormones down-regulate reactive gliosis and astrocyte proliferation after a penetrating brain injury

Cited by 215 publications

References 61 publications

17β-Estradiol Confers Protection after Traumatic Brain Injury in the Rat and Involves Activation of G Protein-Coupled Estrogen Receptor 1

17β-Estradiol Confers Protection after Traumatic Brain Injury in the Rat and Involves Activation of G Protein-Coupled Estrogen Receptor 1

Neuroactive steroids, their metabolites, and neuroinflammation

Estrogen and schizophrenia in women: animal models lend a hand in understanding cognition

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