Progesterone suppresses the inflammatory response and nitric oxide synthase-2 expression following cerebral ischemia

Gibson, Claire L.; Constantin, Despina; Prior, M. J. W.; Bath, Philip M.W.; Murphy, Seán

doi:10.1016/j.expneurol.2005.01.009

Cited by 145 publications

(141 citation statements)

References 57 publications

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“…[4][5][6][7][8][9][10][11][12][13][14] Progesterone has already been shown to be safe and effective for several clinical applications, e.g., hormone replacement therapy, and a variety of preparations are available for different modes of administration. 15 Furthermore, no severe adverse effects have been reported even when progesterone was used at high dose.…”

Section: Introductionmentioning

confidence: 99%

“…Studies assessing the safety and efficacy of progesterone in preclinical models of stroke [4][5][6][7][8][9]13,[20][21][22] have previously been integrated in a systematic review and meta-analysis based on published summary ('group') data. 14 However, this systematic review suggested that key questions remained to be answered, including demonstrating efficacy as a function of sex and age, and evaluating the dose and timing of progesterone administration.…”

Section: Introductionmentioning

confidence: 99%

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Progesterone Treatment for Experimental Stroke: An Individual Animal Meta-Analysis

Wong

Renton

Gibson

et al. 2013

J Cereb Blood Flow Metab

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Preclinical studies suggest progesterone is neuroprotective after cerebral ischemia. The gold standard for assessing intervention effects across studies within and between subgroups is to use meta-analysis based on individual animal data (IAD). Preclinical studies of progesterone in experimental stroke were identified from searches of electronic databases and reference lists. Corresponding authors of papers of interest were contacted to obtain IAD and, if unavailable, summary data were obtained from the publication. Data are given as standardized mean differences (SMDs, continuous data) or odds ratios (binary data), with 95% confidence intervals (95% CIs). In an unadjusted analysis of IAD and summary data, progesterone reduced standardized lesion volume (SMD À 0.766, 95% CI À 1.173 to À 0.358, Po0.001). Publication bias was apparent on visual inspection of a Begg's funnel plot on lesion volume and statistically using Egger's test (P ¼ 0.001). Using individual animal data alone, progesterone was associated with an increase in death in adjusted analysis (odds ratio 2.64, 95% CI 1.17 to 5.97, P ¼ 0.020). Although progesterone significantly reduced lesion volume, it also appeared to increase the incidence of death after experimental stroke, particularly in young ovariectomized female animals. Experimental studies must report the effect of interactions on death and on modifiers, such as age and sex.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Progesterone Treatment for Experimental Stroke: An Individual Animal Meta-Analysis

Wong

Renton

Gibson

et al. 2013

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

show abstract

“…As mentioned previously, cerebral ischemia triggers infl ammatory processes (Herd and Page , 1994 ;Gibson et al , 2005 ;Wang et al , 2007 ). The fi rst infl ammatory cells that enter the brain subsequent to trauma are neutrophils, followed by monocytes, and later on, resident microglia, astrocytes, and neurons are also activated (Morganti -Kossmann et al, 2001 ).…”

Section: Infl Ammationmentioning

confidence: 88%

“…This cascade of events is dependent on variables, such as onset and duration of ischemia, effectiveness of reperfusion, and resultant infarct size or tissue loss (Danton and Dietrich , 2003 ;Gibson et al , 2005 ;Brouns and De Deyn , 2009 ;Saenger and Christenson , 2010 ).…”

Section: Cerebral Ischemiamentioning

confidence: 99%

“…It is well known that thrombotic events are the most common cause of stroke and resultant cerebral ischemia (Braeuninger and Kleinschnitz , 2009 ). Furthermore, it is known that cerebral ischemia triggers a cascade of infl ammatory processes, among others (Herd and Page , 1994 ;Gibson et al , 2005 ;Wang et al , 2007 ). Infl ammation again causes an alteration in platelet activation (Camera et al , 1999 ;Butenas and Mann , 2002 ) and possibly further thrombotic events.…”

Section: Introductionmentioning

confidence: 99%

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Interrelation between inflammation, thrombosis, and neuroprotection in cerebral ischemia

Spuy¹,

Pretorius²

2012

Reviews in the Neurosciences

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Stroke by mechanism of thrombotic cerebral ischemia is one of the leading causes of death and/or disability worldwide. Current research is under consensus that there are sex-based differences in both the prevalence and presentation of stroke and thrombosis. Here we discuss the interrelation between thrombosis and infl ammation and call attention to points in the cerebral ischemic cascade where estrogen may be involved in neuroprotection. Cerebral ischemia triggers a series of events including infl ammation, which is deeply interrelated with thrombosis; infl ammation not only produces local thrombosis, but thrombosis can also amplify infl ammation especially through the synergism of leukocyte and platelet activity. Research involving experimental animal models of cerebral ischemia has shown that sex hormones, especially estrogen, offer a degree of neuroprotection. Mechanisms of this neuroprotection may be linked to certain anti-infl ammatory properties of estrogen, as well as estrogen ' s regulation of thrombosis through the lowering of coagulation factors, among others. It is also understood that sex hormones alter the function and morphology of platelets and fi brin networks, and changes in platelet and fi brin network morphology offer one of the earliest confi rmations of infl ammation. Sex hormone levels, infl ammatory processes, and thrombotic mechanisms are profoundly interconnected in predicting the outcome of cerebral ischemia.

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A place for ultrastructural analysis of platelets in cerebral ischemic research

Spuy

Pretorius

2013

Microscopy Res & Technique

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It is well known that estrogen is neuroprotective through various mechanisms which suggest that sex hormone levels, thrombotic mechanisms, and inflammatory processes are strongly interconnected in predicting the outcome and consequences of cerebral ischemia. Because platelet ultrastructure is altered in conditions like thrombosis and associated with stroke, the question arises whether ultrastructural analyses of platelet morphology may provide further insight into the role of estrogen during ischemic insult. In the current study, a hyperglycemic modification to the two-vessel occlusion model for inducing experimental cerebral ischemia was employed, in order to correlate neural tissue integrity levels between three experimental groups to corresponding platelet ultrastructure so as to determine whether there is an association between cerebral ischemia and the presence of inflammatory or necrotic platelet ultrastructure. It is apparent in the results that under the influence of estrogen in cyclic or intact females, there is lesser neural tissue damage as well as a reduced degree of inflammation evident in platelet activation morphology when compared to males and acyclic or ovariectomized females. It is unmistakable that neural injury is closely shadowed, if not preceded, by inflammatory changes in the coagulation system, particularly manifested in platelet ultrastructure. It is therefore suggested that platelets may indeed be used successfully to follow the progression of events of cerebral ischemia and possibly assist in the assessment of treatment strategies and their effects on hemostasis.

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Progesterone suppresses the inflammatory response and nitric oxide synthase-2 expression following cerebral ischemia

Cited by 145 publications

References 57 publications

Progesterone Treatment for Experimental Stroke: An Individual Animal Meta-Analysis

Progesterone Treatment for Experimental Stroke: An Individual Animal Meta-Analysis

Interrelation between inflammation, thrombosis, and neuroprotection in cerebral ischemia

A place for ultrastructural analysis of platelets in cerebral ischemic research

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