Neuroprotective effect of postischemic administration of progesterone in spontaneously hypertensive rats with focal cerebral ischemia

Kumon, Yoshiaki; Kim, Soon C.; Tompkins, Paul; Stevens, Alan; Sakaki, Saburo; Loftus, Christopher M.

doi:10.3171/jns.2000.92.5.0848

Cited by 119 publications

(78 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Altogether, IAD were available for 689 animals. IAD were not shared for six studies in spite of repeated contact with authors; 6,7,12,13,28,29 nevertheless, data from these studies were included in analyses based on summary data. Five studies were excluded, mostly because they did not have data on total lesion volume or vital status, e.g., one study only had data on blood volume collected.…”

Section: Study Flowmentioning

confidence: 99%

“…[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%

See 2 more Smart Citations

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

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.

show abstract

Section: Study Flowmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

“…While the majority of estrogen studies have demonstrated neuroprotection in various ischemia models, two recent papers studying progesterone in stroke models present contrasting results (Kumon et al, 2000;Murphy et al, 2000). Kumon and colleagues (2000) reported an improvement in neurological deficits and reductions in infarct volume with an administration of progesterone as late as 7 days after transient MCAO.…”

Section: Gendermentioning

confidence: 99%

Pathophysiology of Cerebral Ischemia and Brain Trauma: Similarities and Differences

Bramlett

Dietrich

2004

J Cereb Blood Flow Metab

569

358

View full text Add to dashboard Cite

Summary: Current knowledge regarding the pathophysiology of cerebral ischemia and brain trauma indicates that similar mechanisms contribute to loss of cellular integrity and tissue destruction. Mechanisms of cell damage include excitotoxicity, oxidative stress, free radical production, apoptosis and inflammation. Genetic and gender factors have also been shown to be important mediators of pathomechanisms present in both injury settings. However, the fact that these injuries arise from different types of primary insults leads to diverse cellular vulnerability patterns as well as a spectrum of injury processes. Blunt head trauma produces shear forces that result in primary membrane damage to neuronal cell bodies, white matter structures and vascular beds as well as secondary injury mechanisms. Severe cerebral ischemic insults lead to metabolic stress, ionic perturbations, and a complex cascade of biochemical and molecular events ultimately causing neuronal death. Similarities in the pathogenesis of these cerebral injuries may indicate that therapeutic strategies protective following ischemia may also be beneficial after trauma. This review summarizes and contrasts injury mechanisms after ischemia and trauma and discusses neuroprotective strategies that target both types of injuries.

show abstract

“…Since progesterone acts via a core binding protein and alters DNA transcription, its effect on neurons are accordingly diverse, like upregulating the GABA neurotransmitter, decreasing lipid peroxidation and oxidative stress by its antioxidant effect, limiting the expression of inflammatory cytokines and decreasing cellular apoptosis. All of these, mechanisms result in significantly smaller infarct volumes, smaller extension of edema and altogether better neurologic outcomes on rat models [187][188][189]. Other studies proved that progesterone and its metabolite allopregnanolone inhibit MMP and VEGF upregulation, contributing to BBB maintenance [186].…”

Section: Progesteronementioning

confidence: 99%

Hemorrhagic transformation of ischemic stroke

J¹,

Hortobágyi²

2017

Vascul Dis Ther

View full text Add to dashboard Cite

The better understanding of the diverse mechanisms leading to the hemorrhagic transformation of an ischemic stroke is the crucial point in the prevention of this altogether common phenomenon. The different individual risk factors include the anatomical variability of collateral blood supply, age, genetics, body weight, etiology of the occlusion, side of the occluded vessel, renal status, stroke severity, history of high serum glucose or hypertension and hypertension or hyperglycemia at the onset of the stroke, ferritin level, INR, antiplatelet usage or the platelet count etc. All these might contribute to the process of hemorrhagic transformation. These risk factors have been identified by retrospective epidemiological studies and are useful to identify patients who are at high risk for hemorrhagic conversion and help the decision between conservative, thrombolytic or more advanced treatments such as thrombectomy. The modulations of potential molecular targets participating in the process seem to be promising in animal models, but human trials are lacking the breakthrough success so far, both in extending the time frame of the thrombolysis and in replacing the recombinant tissue plasminogen activator (rtPA) as thrombolytic agent.So far, the careful preselection of patients eligible for thrombolytic therapy is the best way to prevent hemorrhagic transformation. The intensive research in the field revealing small but important molecular details are continuously contributing to the better understanding of hemorrhagic transformation with the intention of finding new agents that co-administrated to the rtPA or completely replacing that could decrease the risk of secondary bleeding.The aim of this review is to give comprehensive insight into the process of hemorrhagic transformation of ischemic stroke, starting with basic overview of the penumbra concept and the collateral supply followed by discussion of the recanalisation-reperfusion-hemorrhagic transformation process after vessel occlusion also highlighting the importance of timing and ratio of recanalisation spontaneously and in case of thrombolytic agent administration. We overview the risk factors of hemorrhagic transformation, which may be helpful to physicians to identify high risk patients before rtPA administration. The last part of the work is dealing with future therapeutic possibilities based on the so far revealed molecular mechanisms of hemorrhagic transformation. With the aim to assess the rate and influencing factors on the recanalisation and reperfusion rate 381 patients with large-vessel occlusion was investigated. The patient group involved ones treated with rtPA or treated conservatively. Partial or complete recanalisation was achieved in 121 out of 210 (58%) patients after intravenous rtPA administration. The recanalisation success was more likely if the patient had atrial fibrillation [4] -maybe because cardioembolic clots consists more fibrin and are more likely to reopen by plasmin proteolysis than thrombosis of an atherosclerotic plaq...

show abstract

Neuroprotective effect of postischemic administration of progesterone in spontaneously hypertensive rats with focal cerebral ischemia

Abstract: Administration of progesterone to male rats 2 hours after MCA occlusion reduces ischemic brain damage and improves neurological deficit even 7 days after ischemia.

Cited by 119 publications

References 23 publications

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

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

Pathophysiology of Cerebral Ischemia and Brain Trauma: Similarities and Differences

Hemorrhagic transformation of ischemic stroke

Contact Info

Product

Resources

About