Progesterone down-regulates spinal cord inflammatory mediators and increases myelination in experimental autoimmune encephalomyelitis

Garay, Laura; Deniselle, Marı́a Claudia González; Brocca, M. E.; Lima, Analı́a; Roig, Paulina; Nicola, Alejandro F. De

doi:10.1016/j.neuroscience.2012.09.032

Cited by 62 publications

(47 citation statements)

References 78 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This cytokine, in turn, contributes to sustaining the pathology during the chronic phase of the disease. In line with previous observations in other experimental models of EAE [64,65] , we observed an upregulation of the gene expression of TLR4, NF-κB and IL-1β in the spinal cords of EAE DA rats. DHT treatment was able to significantly reduce the expression of all these parameters, confirming a decreased inflammatory status, possibly mediated by the TLR4/NF-κB pathway.…”

Section: Discussionsupporting

confidence: 92%

Dihydrotestosterone as a Protective Agent in Chronic Experimental Autoimmune Encephalomyelitis

et al. 2015

View full text Add to dashboard Cite

Multiple sclerosis is a chronic inflammatory disease affecting the central nervous system. As reported by clinical observations, variation in hormonal levels might alter disease susceptibility and progression. Specifically, decreased levels of testosterone in males are reported to be permissive for disease onset. Accordingly, testosterone seems to exert protective effects in experimental autoimmune encephalomyelitis (EAE). In this context, it is important to highlight that testosterone is further metabolized into 17ß-estradiol or dihydrotestosterone (DHT). In this study, we aimed to explore the protective effects of DHT treatment in EAE Dark Agouti rats (i.e. an experimental model showing a protracted relapsing EAE). Data obtained 45 days after EAE induction showed that DHT exerts a beneficial effect on clinical scores, coupled with decreased gliosis (i.e. glial fibrillary acidic protein and major histocompatibility complex of class II staining) and inflammation (i.e. translocator protein 18 kDa, interleukin-1ß, Toll-like receptor 4 and nuclear factor-κB expression) in the spinal cord. Moreover, parameters linked to oxidative stress and tissue damage, like thiobarbituric acid-reactive substance levels and Bcl-2-associated X protein expression, and to mitochondrial activity (i.e. content of mitochondrial DNA and proteins), were improved after DHT administration. This neuroactive steroid may be further metabolized into 3a- or 3ß-diol. However, assessment of the levels of these metabolites after DHT treatment seems to suggest that the protective effects observed here are due to DHT itself. Altogether, the present results indicate that DHT was effective in reducing the severity of chronic EAE and, consequently, may represent an interesting perspective for multiple sclerosis treatment.

show abstract

Section: Discussionsupporting

confidence: 92%

Dihydrotestosterone as a Protective Agent in Chronic Experimental Autoimmune Encephalomyelitis

et al. 2015

View full text Add to dashboard Cite

show abstract

“…This is in agreement with previous reports showing that PROG reduces edema formation after traumatic brain injury 16 by decreasing the expression of aquaporin-4 at the zone of injury 52 and by stabilizing the blood-brain barrier with its antioxidant effects. 53 The improvement in tissue preservation and total spinal cord volume may imply a secondary damage reduction, an effect expected given the already described effects of PROG in decreasing inflammation and reactive gliosis 13,22,54,55 reducing oxidative stress 53 and decreasing excitotoxicity via indirect conversion into allopregnenalone. 9,[56][57][58] Further, PROG notably reduced the extension of the hyperintense signal in a rostrocaudal direction.…”

Section: Prog Reduced Secondary Injury and White Matter Pathologymentioning

confidence: 96%

Progesterone Reduces Secondary Damage, Preserves White Matter, and Improves Locomotor Outcome after Spinal Cord Contusion

Garcı́a-Ovejero

GonzálezSusana²,

Paniagua-TorijaBeatriz³

et al. 2014

Journal of Neurotrauma

View full text Add to dashboard Cite

Progesterone is an anti-inflammatory and promyelinating agent after spinal cord injury, but its effectiveness on functional recovery is still controversial. In the current study, we tested the effects of chronic progesterone administration on tissue preservation and functional recovery in a clinically relevant model of spinal cord lesion (thoracic contusion). Using magnetic resonance imaging, we observed that progesterone reduced both volume and rostrocaudal extension of the lesion at 60 days post-injury. In addition, progesterone increased the number of total mature oligodendrocytes, myelin basic protein immunoreactivity, and the number of axonal profiles at the epicenter of the lesion. Further, progesterone treatment significantly improved motor outcome as assessed using the Basso-Bresnahan-Beattie scale for locomotion and CatWalk gait analysis. These data suggest that progesterone could be considered a promising therapeutical candidate for spinal cord injury.

show abstract

“…Progesterone protective effects have been shown for the spinal cord of EAE rodents. Thus, progesterone pretreatment of EAE mice reduces inflammatory cell infiltration, demyelination, microglial activation, axonal loss, astrocytosis, decreases several proinflammatory mediators, prevents neuronal dysfunction and enhances recovery of motor functions (Garay et al, 2007(Garay et al, , 2012. In our experience, steroid administration at the time of EAE induction or in animals with established disease is not effective.…”

Section: Introductionmentioning

confidence: 91%

“…Although sex differences in disease outcome and spinal cord pathology have been reported in rodents with EAE (Voskuhl et al, 1996;Massella et al, 2012), female mice were used to compare present with past results obtained with progesterone in this gender (Garay et al, 2007(Garay et al, , 2008(Garay et al, , 2012. Mice were kept under pathogen-free conditions under a 12:12 h light/dark cycle (lights on 07.00 h), with controlled humidity and temperature (22°C), and fed standard mice chow.…”

Section: Experimental Animalsmentioning

confidence: 99%

Efficacy of the selective progesterone receptor agonist Nestorone for chronic experimental autoimmune encephalomyelitis

Garay

Deniselle

Sitruk-Ware

et al. 2014

Journal of Neuroimmunology

View full text Add to dashboard Cite

Progesterone down-regulates spinal cord inflammatory mediators and increases myelination in experimental autoimmune encephalomyelitis

Cited by 62 publications

References 78 publications

Dihydrotestosterone as a Protective Agent in Chronic Experimental Autoimmune Encephalomyelitis

Dihydrotestosterone as a Protective Agent in Chronic Experimental Autoimmune Encephalomyelitis

Progesterone Reduces Secondary Damage, Preserves White Matter, and Improves Locomotor Outcome after Spinal Cord Contusion

Efficacy of the selective progesterone receptor agonist Nestorone for chronic experimental autoimmune encephalomyelitis

Contact Info

Product

Resources

About