Effect of 17β-estradiol on functional outcome, release of cytokines, astrocyte reactivity and inflammatory spreading after spinal cord injury in male rats

Ritz, Marie‐Françoise; Hausmann, Oliver

doi:10.1016/j.brainres.2008.01.091

Cited by 77 publications

(74 citation statements)

References 62 publications

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“…The GFAP expression increased and reached its maximum level after 3 days, and then decreased to the control level over the remainder of the 2-week experiment. Data from a mammalian CNS injury showed that mouse GFAP expression increased significantly after SCI, reaching a peak at 4 weeks and persisting for months [43][44][45][46]. The effect of reactive astrocytes in mammalian CNS after injury seems to be two-fold: reactive astrocytes play a beneficial role, such as the promotion of synaptic regeneration in the acute stage after CNS injury, but later act as inhibitors of CNS regeneration [47].…”

Section: Discussionmentioning

confidence: 99%

The molecular cloning of glial fibrillary acidic protein in Gekko japonicus and its expression changes after spinal cord transection

Gao

Wang

Liu

et al. 2010

Cellular and Molecular Biology Letters

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The glial fibrillary acidic protein (GFAP) is an astrocyte-specific member of the class III intermediate filament proteins. It is generally used as a specific marker of astrocytes in the central nervous system (CNS). We isolated a GFAP cDNA from the brain and spinal cord cDNA library of Gekko japonicus, and prepared polyclonal antibodies against gecko GFAP to provide useful tools for further immunochemistry studies. Both the real-time quantitative PCR and western blot results revealed that the expression of GFAP in the spinal cord after transection increased, reaching its maximum level after 3 days, and then gradually decreased over the rest of the 2 weeks of the experiment. Immunohistochemical analyses demonstrated that the increase in GFAP-positive labeling was restricted to the white matter rather than the gray matter. In particular, a slight increase in the number of GFAP positive star-shaped astrocytes was detected in the ventral and lateral regions of the white matter. Our results indicate that reactive astrogliosis in the gecko spinal cord took place primarily in the white matter during a short time interval, suggesting that the specific astrogliosis evaluated by GFAP expression might be advantageous in spinal cord regeneration.

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Section: Discussionmentioning

confidence: 99%

The molecular cloning of glial fibrillary acidic protein in Gekko japonicus and its expression changes after spinal cord transection

Gao

Wang

Liu

et al. 2010

Cellular and Molecular Biology Letters

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“…Estrogen was administered in an extremely wide range of doses, from 0.1 mg=kg to 600 mg=kg, and in some cases subsequent dosing was also done. A dose effect was demonstrated in some studies (Cuzzocrea et al, 2008;Ritz and Hausmann, 2008;Yune et al, 2004). In seven of eight studies, the estrogen was started prior to, at the time of, or within 15 min of the injury.…”

Section: )mentioning

confidence: 97%

A Systematic Review of Non-Invasive Pharmacologic Neuroprotective Treatments for Acute Spinal Cord Injury

Kwon

Okon

Hillyer

et al. 2011

Journal of Neurotrauma

223

139

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An increasing number of therapies for spinal cord injury (SCI) are emerging from the laboratory and seeking translation into human clinical trials. Many of these are administered as soon as possible after injury with the hope of attenuating secondary damage and maximizing the extent of spared neurologic tissue. In this article, we systematically review the available pre-clinical research on such neuroprotective therapies that are administered in a non-invasive manner for acute SCI. Specifically, we review treatments that have a relatively high potential for translation due to the fact that they are already used in human clinical applications, or are available in a form that could be administered to humans. These include: erythropoietin, NSAIDs, anti-CD11d antibodies, minocycline, progesterone, estrogen, magnesium, riluzole, polyethylene glycol, atorvastatin, inosine, and pioglitazone. The literature was systematically reviewed to examine studies in which an in-vivo animal model was utilized to assess the efficacy of the therapy in a traumatic SCI paradigm. Using these criteria, 122 studies were identified and reviewed in detail. Wide variations exist in the animal species, injury models, and experimental designs reported in the pre-clinical literature on the therapies reviewed. The review highlights the extent of investigation that has occurred in these specific therapies, and points out gaps in our knowledge that would be potentially valuable prior to human translation.

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“…Previous work examining the protective potential of 17b-estradiol has typically examined only one or two doses, and mainly initiated the estrogen treatment before or immediately after the SCI (Chaovipoch et al, 2006;Cuzzocrea et al, 2008;Ritz and Hausmann, 2008;Sribnick et al, 2005;Webb et al, 2006;Yune et al, 2004). However, failures to examine a doseresponse relationship and appropriate therapeutic window have been discussed as pre-clinical design inadequacies that can limit successful translation of potential therapeutics for SCI (Faden and Stoica, 2007).…”

Section: Implications Of Evaluated Dose Response and Post Spinal Cordmentioning

confidence: 99%

“…Other work has shown that a single injection of a high dose (4 mg=kg) of 17b-estradiol given 15 min and 24 h after SCI to male rats decreased infiltration of macrophages and microglia, decreased myelin loss, and reduced apoptosis by inhibition of calpain activation (Sribnick et al, 2006). Similarly, a single injection of 4 mg=kg of 17b-estradiol immediately after SCI reduced lesion sized and promoted functional recovery (Ritz and Hausmann, 2008). Administration of 300 mg=kg 17b-estradiol to male mice 1 h before and at 3 and 6 h after SCI was shown to reduce apoptosis in the gray and white matter, reduce expression of pro-apoptotic Bax, increase expression of anti-apoptotic Bcl-2, and reduce inflammation.…”

mentioning

confidence: 95%

Effect of Endogenous Androgens on 17β-Estradiol-Mediated Protection after Spinal Cord Injury in Male Rats

Kachadroka

Hall

Niedzielko

et al. 2010

Journal of Neurotrauma

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Several groups have recently shown that 17b-estradiol is protective in spinal cord injury (SCI). Testosterone can be aromatized to 17b-estradiol and may increase estrogen-mediated protection. Alternatively, testosterone has been shown to increase excitotoxicity in models of central nervous system (CNS) injury. These experiments test the hypothesis that endogenous testosterone in male rats alters 17b-estradiol-mediated protection by evaluating a delayed administration over a clinically relevant dose range and manipulating testicular-derived testosterone. Adult male Sprague Dawley rats were either gonadectomized or left gonad-intact prior to SCI. SCI was produced by a midthoracic crush injury. At 30 min post SCI, animals received a subcutaneous pellet of 0.0, 0.05, 0.5, or 5.0 mg of 17b-estradiol, released over 21 days. Hindlimb locomotion was analyzed weekly in the open field. Spinal cords were collected and analyzed for cell death, expression of Bcl-family proteins, and white-matter sparing. Post-SCI administration of the 0.5-or 5.0-mg pellet improved hindlimb locomotion, reduced urinary bladder size, increased neuronal survival, reduced apoptosis, improved the Bax=Bcl-xL protein ratio, and increased white-matter sparing. In the absence of endogenous testicular-derived androgens, SCI induced greater apoptosis, yet 17b-estradiol administration reduced apoptosis to the same extent in gonadectomized and gonadintact male rats. These data suggest that delayed post-SCI administration of a clinically relevant dose of 17b-estradiol is protective in male rats, and endogenous androgens do not alter estrogen-mediated protection. These data suggest that 17b-estradiol is an effective therapeutic intervention for reducing secondary damage after SCI in males, which could be readily translated to clinical trials.

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Effect of 17β-estradiol on functional outcome, release of cytokines, astrocyte reactivity and inflammatory spreading after spinal cord injury in male rats

Cited by 77 publications

References 62 publications

The molecular cloning of glial fibrillary acidic protein in Gekko japonicus and its expression changes after spinal cord transection

The molecular cloning of glial fibrillary acidic protein in Gekko japonicus and its expression changes after spinal cord transection

A Systematic Review of Non-Invasive Pharmacologic Neuroprotective Treatments for Acute Spinal Cord Injury

Effect of Endogenous Androgens on 17β-Estradiol-Mediated Protection after Spinal Cord Injury in Male Rats

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