Progesterone treatment inhibits the inflammatory agents that accompany traumatic brain injury

Pettus, Edward H.; Wright, David W.; Stein, Donald G.; Hoffman, Stuart W.

doi:10.1016/j.brainres.2005.05.004

Cited by 207 publications

(147 citation statements)

References 57 publications

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“…70 Progesterone was effective against oxidative stress in in vitro studies. 71 Progesterone attenuated brain edema 72 and reduced inflammation 73 in rats with brain injury. In male and ovariectomized female rats with brain injury, treatment with progesterone improved their motor and cognitive performance with attenuation of caspase-3 immunoreactivity and reduction of axonal injury.…”

Section: Clinical Studiesmentioning

confidence: 97%

Use of Magnesium in Traumatic Brain Injury

Sen¹,

Gulati

2010

Neurotherapeutics

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Summary: Depletion of magnesium is observed in animal brain and in human blood after brain injury. Treatment with magnesium attenuates the pathological and behavioral changes in rats with brain injury; however, the therapeutic effect of magnesium has not been consistently observed in humans with traumatic brain injury (TBI). Secondary brain insults are observed in patients with brain injury, which adversely affect clinical outcome. Systemic administration studies in rats have shown that magnesium enters the brain; however, inducing hypermagnesemia in humans did not concomitantly increase magnesium levels in the CSF. We hypothesize that the neuroprotective effects of magnesium in TBI patients could be observed by increasing its brain bioavailability with mannitol. Here, we review the role of magnesium in brain injury, preclinical studies in brain injury, clinical safety and efficacy studies in TBI patients, brain bioavailability studies in rat, and pharmacokinetic studies in humans with brain injury. Neurodegeneration after brain injury involves multiple biochemical pathways. Treatment with a single agent has often resulted in poor efficacy at a safe dose or toxicity at a therapeutic dose. A successful neuroprotective therapy needs to be aimed at homeostatic control of these pathways with multiple agents. Other pharmacological agents, such as dexanabinol and progesterone, and physiological interventions, with hypothermia and hyperoxia, have been studied for the treatment of brain injury. Treatment with magnesium and hypothermia has shown favorable outcome in rats with cerebral ischemia. We conclude that coadministration of magnesium and mannitol with pharmacological and physiological agents could be an effective neuroprotective regimen for the treatment of TBI.

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Section: Clinical Studiesmentioning

confidence: 97%

Use of Magnesium in Traumatic Brain Injury

Sen¹,

Gulati

2010

Neurotherapeutics

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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%

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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“…89 This inhibition of apoptosis may, in part, account for the reduced axonal damage observed in white matter after TBI following treatment with progesterone. 90 The fact that progesterone reduces inflammation after TBI 91 may also contribute to the widely observed beneficial effects of the hormone on edema. Administration of progesterone after brain injury attenuated edema in both female and male animals, 92,93 irrespective of estrogen.…”

Section: Progesteronementioning

confidence: 99%

Multifunctional Drugs for Head Injury

2009

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Summary: Traumatic brain injury (TBI) remains one of the leading causes of mortality and morbidity worldwide in individuals under the age of 45 years, and, despite extensive efforts to develop neuroprotective therapies, there has been no successful outcome in any trial of neuroprotection to date. In addition to recognizing that many TBI clinical trials have not been optimally designed to detect potential efficacy, the failures can be attributed largely to the fact that most of the therapies investigated have been targeted toward an individual injury factor. The contemporary view of TBI is that of a very heterogenous type of injury, one that varies widely in etiology, clinical presentation, severity, and pathophysiology. The mechanisms involved in neuronal cell death after TBI involve an interaction of acute and delayed anatomic, molecular, biochemical, and physiological events that are both complex and multifaceted. Accordingly, neuropharmacotherapies need to be targeted at the multiple injury factors that contribute to the secondary injury cascade, and, in so doing, maximize the likelihood of a successful outcome. This review focuses on a number of such multifunctional compounds that have shown considerable success in experimental studies and that show maximum promise for success in clinical trials.

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Progesterone treatment inhibits the inflammatory agents that accompany traumatic brain injury

Cited by 207 publications

References 57 publications

Use of Magnesium in Traumatic Brain Injury

Use of Magnesium in Traumatic Brain Injury

Neuroactive steroids, their metabolites, and neuroinflammation

Multifunctional Drugs for Head Injury

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