The neuroprotective effects of progesterone on traumatic brain injury: current status and future prospects

Wei, Jing; Gao, Xiao

doi:10.1038/aps.2013.160

Cited by 68 publications

(52 citation statements)

References 51 publications

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“…In the past decade, the potential neuroprotective effects of progesterone after TBI have gained increasing attention [56, 57]. Progesterone rapidly crosses the blood–brain barrier and has several properties that make for a potentially useful pharmacological therapy after TBI, including antioxidant, anti-inflammatory, and remyelination effects after injury [58].…”

Section: Pharmacological Agents With Mixed Results After Tbimentioning

confidence: 99%

Pharmacologic Neuroprotection for Functional Outcomes After Traumatic Brain Injury: A Systematic Review of the Clinical Literature

et al. 2016

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Introduction Traumatic brain injury (TBI) is a major cause of death and disability worldwide. The deleterious effects of secondary brain injury may be attenuated by early pharmacological therapy in the emergency room and intensive care unit (ICU). Current medical management of acute TBI is primarily supportive, aimed at reducing intracranial pressure (ICP) and optimizing cerebral perfusion. There are no pharmacological therapies to date that have been unequivocally demonstrated to improve neurological outcomes after TBI. Objectives The purpose of this systematic review was to evaluate the recent clinical studies from January 2013 through November 2015 that investigated neuroprotective functional outcomes of pharmacological agents after TBI. Methods The following databases were searched for relevant studies: MEDLINE (OvidSP January Week 1, 2013–November Week 2 2015), Embase (OvidSP 2013 January 1–2015 November 24), and the unindexed material in PubMed (National Library of Medicine/National Institutes of Health [NLM/NIH]). This systematic review included only full-length clinical studies and case series that included at least five patients and were published in the English language. Only studies that examined functional clinical outcomes were included. Results Twenty-five of 527 studies met our inclusion criteria, which investigated 15 independent pharmacological therapies. Eight of these therapies demonstrated possible neuroprotective properties and improved functional outcomes, of which five were investigated with randomized clinical trials: statins, N-acetyl cysteine (NAC), Enzogenol, Cerebrolysin, and nitric oxide synthase inhibitor (VAS203). Three pharmacological agents did not demonstrate neuroprotective effects, and four agents had mixed results. Conclusions While there is currently no single pharmacological therapy that will unequivocally improve clinical outcomes after TBI, several agents have demonstrated promising clinical benefits for specific TBI patients and should be investigated further.

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Section: Pharmacological Agents With Mixed Results After Tbimentioning

confidence: 99%

Pharmacologic Neuroprotection for Functional Outcomes After Traumatic Brain Injury: A Systematic Review of the Clinical Literature

et al. 2016

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“…Among its neuro protective effects, progesterone down-regulates the synthesis of proinflammatory cytokines as well as decreasing immune cell migration and proliferation after TBI. 74 Tw o Phase II clinical trials suggest that progesterone administration in humans may improve survival; however, a Phase III efficacy trial was recently halted for futility (ProTECT III). 75,76 One important criticism of both the HS trial and ProTECT III has been the use of Glasgow Outcome Scale Extended as the primary outcome.…”

Section: Sex Steroidsmentioning

confidence: 99%

Clinical evidence of inflammation driving secondary brain injury

Hinson

Rowell

Schreiber

2015

Journal of Trauma and Acute Care Surgery

159

125

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Background Despite advances in both prevention and treatment, traumatic brain injury (TBI) remains one of the most burdensome diseases; 2% of the US population currently lives with disabilities resulting from TBI. Recent advances in the understanding of inflammation and its impact on the pathophysiology of trauma have increased the interest in inflammation as a possible mediator in TBI outcome. Objectives The goal of this systematic review is to address the question: “What is the evidence in humans that inflammation is linked to secondary brain injury?” As the experimental evidence has been well described elsewhere, this review will focus on the clinical evidence for inflammation as a mechanism of secondary brain injury. Data Sources Medline database (1996-Week 1 June 2014), Pubmed and Google Scholar databases were queried for relevant studies. Study Eligibility Criteria Studies were eligible if participants were adults and/or children who sustained moderate or severe TBI in the acute phase of injury, published in English. Studies published in the last decade (since 2004) were preferentially included. Trials could be observational or interventional in nature. Appraisal and Synthesis Methods To address the quality of the studies retrieved, we applied the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) criteria to assess the limitations of the included studies. Results Trauma initiates local central nervous system as well as systemic immune activation. Numerous observational studies describe elevation of pro-inflammatory cytokines that are associated with important clinical variables including neurologic outcome and mortality. A small number of clinical trials have included immunomodulating strategies, but no intervention to date has proven effective in improving outcomes after TBI. Limitations Inclusion of studies not initially retrieved by the search terms may have biased our results. Additionally, some reports may have been inadvertently excluded due to use of non-search term key words. Conclusions and Implications of Key Findings Clinical evidence of inflammation causing secondary brain injury in humans is gaining momentum. While inflammation is certainly present, it is not clear from the literature at what juncture inflammation becomes maladaptive, promoting secondary injury rather than facilitating repairand identifying patients with maladaptive inflammation (neuro-inflammation, systemic, or both) after TBI remains elusive. Direct agonism/antagonism represents an exciting target for future study. Level of Evidence Systematic review, level III.

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“…A detailed discussion of the neuroactive effects of progesterone, either alone or in combination with estrogen, is beyond the scope of this review and has been extensively discussed elsewhere. The authors direct interested readers to several excellent reviews on this subject (Deutsch et al, 2013; Wei and Xiao, 2013). …”

Section: Introduction: the Role Of Estrogen Beyond The Gonadsmentioning

confidence: 99%

Estrogens as neuroprotectants: Estrogenic actions in the context of cognitive aging and brain injury

Engler-Chiurazzi

Brown

Povroznik

et al. 2017

Progress in Neurobiology

175

121

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There is ample empirical evidence to support the notion that the biological impacts of estrogen extend beyond the gonads to other bodily systems, including the brain and behavior. Converging preclinical findings have indicated a neuroprotective role for estrogen in a variety of experimental models of cognitive function and brain insult. However, the surprising null or even detrimental findings of several large clinical trials evaluating the ability of estrogen-containing hormone treatments to protect against age-related brain changes and insults, including cognitive aging and brain injury, led to hesitation by both clinicians and patients in the use of exogenous estrogenic treatments for nervous system outcomes. That estrogen-containing therapies are used by tens of millions of women for a variety of health-related applications across the lifespan has made identifying conditions under which benefits with estrogen treatment will be realized an important public health issue. Here we provide a summary of the biological actions of estrogen and estrogen-containing formulations in the context of aging, cognition, stroke, and traumatic brain injury. We have devoted special attention to highlighting the notion that estrogen appears to be a conditional neuroprotectant whose efficacy is modulated by several interacting factors. By developing criteria standards for desired beneficial peripheral and neuroprotective outcomes among unique patient populations, we can optimize estrogen treatments for attenuating the consequences of, and perhaps even preventing, cognitive aging and brain injury.

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The neuroprotective effects of progesterone on traumatic brain injury: current status and future prospects

Cited by 68 publications

References 51 publications

Pharmacologic Neuroprotection for Functional Outcomes After Traumatic Brain Injury: A Systematic Review of the Clinical Literature

Pharmacologic Neuroprotection for Functional Outcomes After Traumatic Brain Injury: A Systematic Review of the Clinical Literature

Clinical evidence of inflammation driving secondary brain injury

Estrogens as neuroprotectants: Estrogenic actions in the context of cognitive aging and brain injury

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