Pinocembrin attenuates hemorrhagic transformation after delayed t-PA treatment in thromboembolic stroke rats by regulating endogenous metabolites

Kong, Ling-Lei; Gao, Li; Wang, Kexin; Liu, Nannan; Liu, Chengdi; Ma, Guodong; Yang, Haiguang; Qin, Xuemei; Du, Guanhua

doi:10.1038/s41401-021-00664-x

Cited by 12 publications

(7 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The natural product pinocembrin possesses pleiotropic neuroprotective effects and is currently in a phase II clinical trial for ischemic stroke. Pinocembrin exerts anti-inflammatory effects by inhibiting the activation of the TLR4/NF-κB pathway and the activation of m1 phenotype microglia, in addition to reducing the hemorrhagic transformation that results from t-PA treatment [ 76 , 77 ]. Berberine, a compound extracted from Coptis chinensis, has good antibacterial and anti-inflammatory properties.…”

Section: Introductionmentioning

confidence: 99%

Targeting pyroptosis as a preventive and therapeutic approach for stroke

Long

Sun

et al. 2023

Cell Death Discov.

View full text Add to dashboard Cite

Stroke has caused tremendous social stress worldwide, yet despite decades of research and development of new stroke drugs, most have failed and rt-PA (Recombinant tissue plasminogen activator) is still the accepted treatment for ischemic stroke. the complexity of the stroke mechanism has led to unsatisfactory efficacy of most drugs in clinical trials, indicating that there are still many gaps in our understanding of stroke. Pyroptosis is a programmed cell death (PCD) with inflammatory properties and are thought to be closely associated with stroke. Pyroptosis is regulated by the GSDMD of the gasdermin family, which when cleaved by Caspase-1/Caspase-11 into N-GSDMD with pore-forming activity can bind to the plasma membrane to form small 10–20 nm pores, which would allow the release of inflammatory factors IL-18 and IL-1β before cell rupture, greatly exacerbating the inflammatory response. The pyroptosis occurs mainly in the border zone of cerebral infarction, and glial cells, neuronal cells and brain microvascular endothelial cells (BMECs) all undergo pyroptosis after stroke, which largely exacerbates the breakdown of the blood-brain barrier (BBB) and thus aggravates brain injury. Therefore, pyroptosis may be a good direction for the treatment of stroke. In this review, we focus on the latest mechanisms of action of pyroptosis and the process by which pyroptosis regulates stroke development. We also suggest potential therapeutic stroke drugs that target the pyroptosis pathway, providing additional therapeutic strategies for the clinical management of stroke.

show abstract

Section: Introductionmentioning

confidence: 99%

Targeting pyroptosis as a preventive and therapeutic approach for stroke

Long

Sun

et al. 2023

Cell Death Discov.

View full text Add to dashboard Cite

show abstract

“…In another study, 16 metabolites were differentially expressed in the serum of rats subjected to ischemia with electrocoagulation‐induced thrombosis and tissue plasminogen activator (t‐PA) induced‐thrombolysis. From these, lactic acid was the most promising candidate to be used as a biomarker for hemorrhagic transformation after t‐PA treatment 64 …”

Section: Resultsmentioning

confidence: 99%

“…From these, lactic acid was the most promising candidate to be used as a biomarker for hemorrhagic transformation after t-PA treatment. 64…”

Section: Metabolitesmentioning

confidence: 99%

Fluid biomarkers in stroke: From animal models to clinical care

Dias

Silva

Moura

et al. 2022

Acta Neuro Scandinavica

View full text Add to dashboard Cite

Stroke is a leading cause of death and disability worldwide. Stroke prevention, early diagnosis, and efficient acute treatment are priorities to successfully impact stroke death and disability. Fluid biomarkers may improve stroke differential diagnostic, patient stratification for acute treatment, and post‐stroke individualized rehabilitation. In the present work, we characterized the use of stroke animal models in fluid biomarker research through a systematic review of PubMed and Scopus databases, followed by a literature review on the translation to the human stroke care setting and future perspectives in the field. We found increasing numbers of publications but with limited translation to the clinic. Animal studies are very heterogeneous, do not account for several human features present in stroke, and, importantly, only a minority of such studies used human cohorts to validate biomarker findings. Clinical studies have found appealing candidates, both protein and circulating nucleic acids, to contribute to a more personalized stroke care pathway. Still, brain tissue complexity and the fact that different brain pathologies share lesion biomarkers make this task challenging due to biomarker low specificity. Moreover, the study design and lack of validation cohorts may have precluded a formal integration of biomarkers in different steps of stroke diagnosis and treatment. To overcome such issues, recent pivotal studies on biomarker dynamics in individual patients are providing added value to diagnosis and anticipating patients' early prognosis. Presently, the most consistent protein biomarkers for stroke diagnosis and short‐ and long‐term prognosis are associated with tissue damage at neuronal (TAU), axonal (NFL), or astroglial (GFAP and S100β) levels. Most promising nucleic acids are microRNAs (miR), due to their stability in plasma and ease of access. Still, clinical validation and standardized quantitation place them a step behind compared protein as stroke biomarkers. Ultimately, the definition of clinically relevant biomarker panels and optimization of fast and sensitive biomarker measurements in the blood, together with their combination with clinical and neuroimaging data, will pave the way toward personalized stroke care.

show abstract

“…The above research results suggested that serum LDH has substantial predictive value in various disorders of other systems. Previous studies revealed that LDH also played a role in central nervous system diseases [9,10,16,18]. According to a survey based on proteomics analysis, serum LDH was found to independently predict the formation of early hematomas in individuals with spontaneous intracerebral hemorrhage [10].…”

Section: Discussionmentioning

confidence: 99%

Lactate Dehydrogenase Predicts Hemorrhagic Transformation in Patients with Acute Ischemic Stroke

Chen¹,

Xu²,

Huang³

et al. 2023

Gerontology

View full text Add to dashboard Cite

Introduction: Hemorrhagic transformation (HT) is a severe but frequent complication of acute ischemic stroke (AIS). This study aimed to evaluate the relationship between serum LDH levels and HT. Methods: We retrospectively included 542 AIS patients with HT and 1091 age and gender-matched patients without HT. Demographic and clinical data were obtained from medical records, and blood samples were obtained within 24 hours after admission. The characteristics of groups were compared. With the receiver operating characteristic curve (ROC) analysis, we assessed the discriminating capacity of LDH levels in predicting HT in patients with AIS. The logistic regression model was used to determine the connection between LDH and HT. Results: The HT group had considerably higher LDH levels than the non-HT group [263.0 (216.0-323.3) U/L vs. 178.0 (162.0-195.0) U/L, P < 0.001]. We also observed that the levels of LDH in the parenchymal hemorrhage (PH) subgroup were significantly higher than those in the hemorrhagic infarction (HI) subgroup [281.0 (230.0-340.0) U/L vs. 258.0 (209.0-311.0) U/L, P < 0.001]. The area under the ROC curve (AUC) of LDH was 0.890 (95% CI 0.874-0.905, P < 0.001). Besides, logistic regression revealed that high LDH levels (LDH > 215 U/L) showed a higher risk of HT [odds ratio (OR) = 10.958, 95% confidence level (CI) 7.964-15.078, P < 0.001]. Conclusion: High LDH levels were linked with an increased risk of HT in AIS patients. Practical measures should be considered in patients with increased LDH levels (LDH > 215 U/L).

show abstract

Pinocembrin attenuates hemorrhagic transformation after delayed t-PA treatment in thromboembolic stroke rats by regulating endogenous metabolites

Cited by 12 publications

References 45 publications

Targeting pyroptosis as a preventive and therapeutic approach for stroke

Targeting pyroptosis as a preventive and therapeutic approach for stroke

Fluid biomarkers in stroke: From animal models to clinical care

Lactate Dehydrogenase Predicts Hemorrhagic Transformation in Patients with Acute Ischemic Stroke

Contact Info

Product

Resources

About