Intracerebral hemorrhage (ICH), a severe hemorrhagic stroke, induces cerebral oxidative stress and severe secondary neurological injury. Curcumin was demonstrated to inhibit oxidative stress in the brain after ICH. However, the pharmacological mechanism needs further research. We used an intrastriatal injection of autologous blood to make the rat ICH model, and then the rat was treated with curcumin (100 mg/kg/day). Modified Neurological Severity Score (mNSS) and corner test results showed that curcumin could significantly promote the neurological recovery of ICH rats. Meanwhile, curcumin could substantially reduce ROS and MDA in the tissues around intracranial hematoma and prevent GSH depletion. To explore the pharmacological molecular mechanism of curcumin, we used HAPI cells and primary rat cortical microglia for in vitro experiments. In vitro, heme-treated cells were used as the cell model of ICH to explore the molecular mechanism of inhibiting oxidative stress by curcumin treatment. The results showed that curcumin significantly inhibited heme-induced oxidative stress, decreased intracellular ROS and MDA, and promoted Nrf2 and its downstream antioxidant gene (HO-1, NQO1, and Gpx4) expression. These results suggest that curcumin inhibits oxidative stress by activating the Nrf2/HO-1 pathway. Here, our results indicate that curcumin can promote the inhibition of oxidative stress in microglia by activating the Nrf2/HO-1 pathway and promoting neurological recovery after ICH, providing a new therapeutic target for clinical treatment of ICH.

Background: Microbubbles are widely used as highly effective contrast agents to improve the diagnostic capability of ultrasound imaging. Mounting evidence suggests that ultrasound coupled with microbubbles has promising therapeutic applications in cancer, cardiovascular, and neurological disorders by acting as gene or drug carriers. The aim of this study was to identify the scientific output and activity related to ultrasound microbubble through bibliometric approaches.Methods: The literature related to ultrasound microbubble published between 1998 and 2019 was identified and selected from the Science Citation Index Expanded of Web of Science Core Collection on February 21, 2021. The Scopus database was also searched to validate the results and provided as supplementary material. Quantitative variables including number of publications and citations, H-index, and journal citation reports were analyzed by using Microsoft Excel 2019 and GraphPad Prism 8.0 software. VOS viewer and CiteSpace V were used to perform coauthorship, citation, co-citation, and co-occurrence analysis for countries/regions, institutions, authors, and keywords.Results: A total of 6088 publications from the WoSCC were included. The United States has made the largest contribution in this field, with the majority of publications (2090, 34.3%), citations (90,741, 46.6%), the highest H-index (138), and close collaborations with China and Canada. The most contributive institution was the University of Toronto. Professors De Jong N and Dayton P A have made great achievements in this field. However, the research cooperation between institutions and authors was relatively weak. All the studies could be divided into four clusters: “ultrasound diagnosis study,” “microbubbles’ characteristics study,” “gene therapy study,” and “drug delivery study.” The average appearing years (AAY) of keywords in the cluster “drug delivery study” was more recent than other clusters. For promising hot spots, “doxorubicin” showed a relatively latest AAY of 2015.49, followed by “nanoparticles” and “breast cancer.”Conclusion: There has been an increasing amount of scientific output on ultrasound microbubble according to the global trends, and the United States is staying ahead in this field. Collaboration between research teams still needs to be strengthened. The focus gradually shifts from “ultrasound diagnosis study” to “drug delivery study.” It is recommended to pay attention to the latest hot spots, such as “doxorubicin,” “nanoparticles,” and “breast cancer.”

Background: The management of various central nervous system (CNS) disorders has been challenging, due to highly compact blood-brain barrier (BBB) impedes the access of most pharmacological agents to the brain. Among multiple strategies proposed to circumvent this challenge, intranasal delivery route has sparked great interest for brain targeting in the past decades. The aim of this study was to apply scientometric method to estimate the current status and future trends of the field from a holistic perspective.Methods: All relevant publications during 1998–2020 were retrieved from the Web of Science Core Collection (SCIE, 1998-present). Two different scientometric software including VOS viewer and CiteSpace, and one online platform were used to conduct co-authorship, co-citation, and co-occurrence analysis of journals, countries, institutes, authors, references and keywords.Results: A total of 2,928 documents, including 2,456 original articles and 472 reviews, were retrieved. Our analysis revealed a significant increasing trend in the total number of scientific publications over the past 2 decades (R² = 0.98). The United States dominated the field, reflecting in the largest amount of publications (971), the highest H-index (99), and extensive international collaboration. Jamia Hamdard contributed to most publications. Frey WH and Illum L were key researchers with the highest number of publications and citations, respectively. The International Journal of Pharmaceutics was the most influential academic journal, and Pharmacology/Pharmacy and Neurosciences/Neurology were the hottest research categories in this field. Based on keywords occurrence analysis, four main topics were identified, and the current research focus of this field has shifted from cluster 4 (pathways and mechanisms of intranasal delivery) to cluster 2 (the study of nasal drug delivery systems), especially the nanostructured and nano-sized carrier systems. Keywords burst detection revealed that the research focus on oxidative stress, drug delivery, neuroinflammation, nanostructured lipid carrier, and formulation deserves our continued attention.Conclusion: To the authors’ knowledge, this is the first scientometric analysis regarding intranasal delivery research. This study has demonstrated a comprehensive knowledge map, development landscape and future directions of intranasal delivery research, which provides a practical and valuable reference for scholars and policymakers in this field.

Background: Ferroptosis is a newly proposed form of programmed cell death, and accumulating evidence suggests that it plays an essential role in the development of multiple diseases, especially cancers and neurodegenerative diseases. Since officially named in 2012, research on ferroptosis has grown rapidly. There are previous reviews focused on the research progress of ferroptosis from a certain aspect, but no bibliometric studies summarizing this field as a whole. This study aimed to assess the scientific output and activity regarding ferroptosis research from a global perspective.Methods: Publications related to ferroptosis from 2012 to 2020 were identified and selected from the Web of Science Core Collection. Excel 2019 and GraphPad Prism 8.0 was used to analyze quantitative variables including number of publications and citations, H-index, and journal citation reports. VOS viewer and CiteSpace were used to perform co-authorship, co-citation, and co-occurrence analysis of countries/institutes/authors/keywords.Results: A total of 1,285 publications on ferroptosis research were identified. The literature on ferroptosis had been continuously growing since 2012, and the expansion might continue at a rapid pace in the following years. China contributed the greatest proportion (43.74%) of ferroptosis publications, and the United States ranked first in the number of citation frequency (20,980 times) and H-index (70). B. R. Stockwell, D. L. Tang, and R. Kang were key researchers. The journal Cell Death Disease published the highest number of articles, with 42 articles. All the keywords could be divided into two clusters: cluster 1 (pathway and mechanism) and cluster 2 (treatment and effect). In terms of potential hotspots, keywords with the strong bursts and still ongoing recently were “neurodegeneration” (2017–2020), “chemotherapy” (2017–2020), “NF-kappa B” (2017–2020), and “photodynamic therapy” (2018–2020).Conclusion: There will be a dramatically increasing number of publications on ferroptosis research based on the current global trends. China has made significant progress in ferroptosis research, but the United States is actually dominated in this field. More focus will be placed on neurodegeneration, chemotherapy, nuclear factor κB, and photodynamic therapy, which may be the next popular topics in ferroptosis research.

Background: Among the effective approaches developed for blood-brain barrier (BBB) opening, ultrasound is recognized as a non-invasive technique that can induce localized BBB opening transiently and repeatedly. This technique has aroused broad attention from researchers worldwide, and numerous articles have been published recently. However, no existing study has systematically examined this field from a scientometric perspective. The aim of this study was to summarize the knowledge structure and identify emerging trends and potential hotspots in this field.Methods: Publications related to ultrasound-induced BBB opening published from 1998 to 2020 were retrieved from Web of Science Core Collection. The search strategies were as follows: topic: (“blood brain barrier” OR “BBB”) AND topic: (ultrasound OR ultrason* OR acoustic* OR sonopora*). The document type was set to articles or reviews with language restriction to English. Three different analysis tools including one online platform, VOS viewer1.6.16, and CiteSpace V5.7.R2 software were used to conduct this scientometric study.Results: A total of 1,201 valid records were included in the final analysis. The majority of scientific publication was produced by authors from North America, Eastern Asia, and Western Europe. Ultrasound in Medicine and Biology was the most prominent journal. The USA, China, and Canada were the most productive countries. Hynynen K, and Mcdannold N were key researchers with considerable academic influence. According to analysis of keywords, four main research directions were identified: cluster 1 (microbubbles study), cluster 2 (management of intracranial tumors), cluster 3 (ultrasound parameters and mechanisms study), and cluster 4 (treatment of neurodegenerative diseases). The current research hotspot has shifted from the basic research of ultrasound and microbubbles to management of intracranial tumors and neurodegenerative diseases. Burst detection analysis showed that Parkinson's disease, doxorubicin, gold nanoparticle, glioblastoma, gene therapy, and Alzheimer's disease may continue to be the research frontiers.Conclusion: Ultrasound-induced BBB opening research is in a period of robust development. This study is a starting point, providing a comprehensive overview, development landscape, and future opportunities of this technology, which standout as a useful reference for researchers and decision makers interested in this area.