RIGOR Guidelines: Escalating STAIR and STEPS for Effective Translational Research
TL;DR: The need for good laboratory practices, transparent scientific reporting, and the use of translational research models representative of the disease state to develop effective treatments to treat ischemic and hemorrhagic stroke is emphasized.
Abstract: Stroke continues to be a serious and significant health problem in the USA and worldwide This article will emphasize the need for good laboratory practices, transparent scientific reporting, and the use of translational research models representative of the disease state to develop effective treatments This will allow for the testing and development of new innovative strategies so that efficacious therapies can be developed to treat ischemic and hemorrhagic stroke This article recommends guidelines for effective translational research, most importantly, the need for study blinding, study group randomization, power analysis, accurate statistical analysis, and a conflict of interest statement Additional guidelines to ensure reproducibility of results and confirmation of efficacy in multiple species are discussed
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TL;DR: This review summarizes recent progress concerning the mechanisms involved in brain damage, repair and regeneration related to microglia/macrophage activation and phenotype transition after stroke and argues that future translational studies should be targeting multiple key regulating molecules to improve brain repair.
445 citations
TL;DR: It is found that administration of ferrostatin-1, a specific inhibitor of ferroptosis, prevented neuronal death and reduced iron deposition induced by hemoglobin in organotypic hippocampal slice cultures (OHSCs) and human induced pluripotent stem cell-derived neurons better than any inhibitor alone.
Abstract: Intracerebral hemorrhage (ICH) causes high mortality and morbidity, but our knowledge of post-ICH neuronal death and related mechanisms is limited. In this study, we first demonstrated that ferroptosis, a newly identified form of cell death, occurs in the collagenase-induced ICH model in mice. We found that administration of ferrostatin-1, a specific inhibitor of ferroptosis, prevented neuronal death and reduced iron deposition induced by hemoglobin in organotypic hippocampal slice cultures (OHSCs). Mice treated with ferrostatin-1 after ICH exhibited marked brain protection and improved neurologic function. Additionally, we found that ferrostatin-1 reduced lipid reactive oxygen species production and attenuated the increased expression level of PTGS2 and its gene product cyclooxygenase-2 ex vivo and in vivo. Moreover, ferrostatin-1 in combination with other inhibitors that target different forms of cell death prevented hemoglobin-induced cell death in OHSCs and human induced pluripotent stem cell-derived neurons better than any inhibitor alone. These results indicate that ferroptosis contributes to neuronal death after ICH, that administration of ferrostatin-1 protects hemorrhagic brain, and that cyclooxygenase-2 could be a biomarker of ferroptosis. The insights gained from this study will advance our knowledge of the post-ICH cell death cascade and be essential for future preclinical studies.
442 citations
Cites methods from "RIGOR Guidelines: Escalating STAIR ..."
...All treatment strategies followed ARRIVE and RIGOR guidelines (63)....
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TL;DR: The mechanisms of action of photobiomodulation to the brain are covered, some of the key pre-clinical studies and clinical trials that have been undertaken for diverse brain disorders are summarized, and the possibility that PBM could be used for cognitive enhancement in normal healthy people is summarized.
Abstract: Photobiomodulation (PBM) describes the use of red or near-infrared light to stimulate, heal, regenerate, and protect tissue that has either been injured, is degenerating, or else is at risk of dying. One of the organ systems of the human body that is most necessary to life, and whose optimum functioning is most worried about by humankind in general, is the brain. The brain suffers from many different disorders that can be classified into three broad groupings: traumatic events (stroke, traumatic brain injury, and global ischemia), degenerative diseases (dementia, Alzheimer's and Parkinson's), and psychiatric disorders (depression, anxiety, post traumatic stress disorder). There is some evidence that all these seemingly diverse conditions can be beneficially affected by applying light to the head. There is even the possibility that PBM could be used for cognitive enhancement in normal healthy people. In this transcranial PBM (tPBM) application, near-infrared (NIR) light is often applied to the forehead because of the better penetration (no hair, longer wavelength). Some workers have used lasers, but recently the introduction of inexpensive light emitting diode (LED) arrays has allowed the development of light emitting helmets or "brain caps". This review will cover the mechanisms of action of photobiomodulation to the brain, and summarize some of the key pre-clinical studies and clinical trials that have been undertaken for diverse brain disorders.
350 citations
TL;DR: The vast array of physiological dysfunctions following SAH that ultimately lead to cell death are discussed and a new concept of the vasculo-neuronal-glia triad model for SAH study is highlighted and presents the challenges and opportunities of this model for future SAH applications.
291 citations
Cites background from "RIGOR Guidelines: Escalating STAIR ..."
...It may be prudent to develop a set of guidelines for SAH translational studies (Lapchak et al., 2013)....
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TL;DR: This is the first study suggesting that the poor stroke recovery in aged mice can be reversed via poststroke bacteriotherapy following the replenishment of youthful gut microbiome via modulation of immunologic, microbial, and metabolomic profiles in the host.
Abstract: Rationale: The elderly experience profound systemic responses after stroke, which contribute to higher mortality and more severe long-term disability. Recent studies have revealed that stroke outco...
214 citations
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TL;DR: The Statistical Update brings together the most up-to-date statistics on heart disease, stroke, other vascular diseases, and their risk factors and presents them in its Heart Disease and Stroke Statistical Update each year.
Abstract: Appendix I: List of Statistical Fact Sheets. URL: http://www.americanheart.org/presenter.jhtml?identifier=2007
We wish to thank Drs Brian Eigel and Michael Wolz for their valuable comments and contributions. We would like to acknowledge Tim Anderson and Tom Schneider for their editorial contributions and Karen Modesitt for her administrative assistance.
Disclosures
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# Summary {#article-title-2}
Each year, the American Heart Association, in conjunction with the Centers for Disease Control and Prevention, the National Institutes of Health, and other government agencies, brings together the most up-to-date statistics on heart disease, stroke, other vascular diseases, and their risk factors and presents them in its Heart Disease and Stroke Statistical Update. The Statistical Update is a valuable resource for researchers, clinicians, healthcare policy makers, media professionals, the lay public, and many others who seek the best national data available on disease …
6,176 citations
"RIGOR Guidelines: Escalating STAIR ..." refers background in this paper
...It is now known that brain hemorrhage, SAH, ICH, and IVH occur in approximately 17–20 % of all patients with a stroke [1, 2, 17]....
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TL;DR: As compared with placebo, intravenous alteplase administered between 3 and 4.5 hours after the onset of symptoms significantly improved clinical outcomes in patients with acute ischemic stroke; altePlase was more frequently associated with symptomatic intracranial hemorrhage.
Abstract: Background Intravenous thrombolysis with alteplase is the only approved treatment for acute ischemic stroke, but its efficacy and safety when administered more than 3 hours after the onset of symptoms have not been established. We tested the efficacy and safety of alteplase administered between 3 and 4.5 hours after the onset of a stroke. Methods After exclusion of patients with a brain hemorrhage or major infarction, as detected on a computed tomographic scan, we randomly assigned patients with acute ischemic stroke in a 1:1 double-blind fashion to receive treatment with intravenous alteplase (0.9 mg per kilogram of body weight) or placebo. The primary end point was disability at 90 days, dichotomized as a favorable outcome (a score of 0 or 1 on the modified Rankin scale, which has a range of 0 to 6, with 0 indicating no symptoms at all and 6 indicating death) or an unfavorable outcome (a score of 2 to 6 on the modified Rankin scale). The secondary end point was a global outcome analysis of four neurologic and disability scores combined. Safety end points included death, symptomatic intracranial hemorrhage, and other serious adverse events. Results We enrolled a total of 821 patients in the study and randomly assigned 418 to the alteplase group and 403 to the placebo group. The median time for the administration of alteplase was 3 hours 59 minutes. More patients had a favorable outcome with alte plase than with placebo (52.4% vs. 45.2%; odds ratio, 1.34; 95% confidence interval [CI], 1.02 to 1.76; P = 0.04). In the global analysis, the outcome was also improved with alteplase as compared with placebo (odds ratio, 1.28; 95% CI, 1.00 to 1.65; P<0.05). The incidence of intracranial hemorrhage was higher with alteplase than with placebo (for any intracranial hemorrhage, 27.0% vs. 17.6%; P = 0.001; for symptomatic intracranial hemorrhage, 2.4% vs. 0.2%; P = 0.008). Mortality did not differ significant ly between the alteplase and placebo groups (7.7% and 8.4%, respectively; P = 0.68). There was no significant difference in the rate of other serious adverse events. Conclusions As compared with placebo, intravenous alteplase administered between 3 and 4.5 hours after the onset of symptoms significantly improved clinical outcomes in patients with acute ischemic stroke; alteplase was more frequently associated with symptomatic intracranial hemorrhage. (ClinicalTrials.gov number, NCT00153036.)
5,491 citations
"RIGOR Guidelines: Escalating STAIR ..." refers background in this paper
...Information gained from the repeated testing of tPA [4, 8], and subsequent population analyses should be incorporated into current and future translational development programs....
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...There is also significant information available in the literature regarding the group of refractory diabetic patients enrolled in the NINDS rt-PA trial [8] and the ECASS III trial [4], which includes a small percentage of patients with diabetes (Table 1)....
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TL;DR: The statistical update brings together the most up-to-date statistics on heart disease, stroke, other vascular diseases, and their risk factors and presents them in its Heart Disease and Stroke Statistical Update.
Abstract: We thank Drs Sean Coady, Eric L. Ding, Brian Eigel, Gregg C. Fonarow, Linda Geiss, Cherie James, Michael Mussolino, and Michael Wolz for their valuable comments and contributions. We acknowledge Tim Anderson and Tom Schneider for their editorial contributions, and Karen Modesitt for her administrative assistance.
Disclosures
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# Summary {#article-title-2}
Each year, the American Heart Association, in conjunction with the Centers for Disease Control and Prevention, the National Institutes of Health, and other government agencies, brings together the most up-to-date statistics on heart disease, stroke, other vascular diseases, and their risk factors and presents them in its Heart Disease and Stroke Statistical Update. The Statistical Update is a valuable resource for researchers, clinicians, healthcare policy makers, media professionals, the lay …
5,019 citations
TL;DR: The statistical update brings together the most up-to-date statistics on heart disease, stroke, other vascular diseases, and their risk factors and presents them in its Heart Disease and Stroke Statistical Update.
Abstract: We thank Drs Sean Coady, Eric L. Ding, Brian Eigel, Gregg C. Fonarow, Linda Geiss, Cherie James, Michael Mussolino, and Michael Wolz for their valuable comments and contributions. We acknowledge Tim Anderson and Tom Schneider for their editorial contributions, and Karen Modesitt for her administrative assistance.
Disclosures
⇓⇓⇓⇓
View this table:
Writing Group Disclosures
View this table:
Writing Group Disclosures, Continued
View this table:
Writing Group Disclosures, Continued
View this table:
Writing Group Disclosures, Continued
# Summary {#article-title-2}
Each year, the American Heart Association, in conjunction with the Centers for Disease Control and Prevention, the National Institutes of Health, and other government agencies, brings together the most up-to-date statistics on heart disease, stroke, other vascular diseases, and their risk factors and presents them in its Heart Disease and Stroke Statistical Update. The Statistical Update is a valuable resource for researchers, clinicians, healthcare policy makers, media professionals, the lay …
4,003 citations
"RIGOR Guidelines: Escalating STAIR ..." refers background in this paper
...It is now known that brain hemorrhage, SAH, ICH, and IVH occur in approximately 17–20 % of all patients with a stroke [1, 2, 17]....
[...]
...Patients with diabetes have been shown to be independently associated with poor neurological outcome and higher mortality in the absence of thrombolytic treatment [43–45], and among patients treated with intravenous tPA [8], the presence of diabetes significantly reduces the odds of favorable outcome at 3 months [17]....
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