VOSviewer is a method to manage and visualize knowledge structures [5] Here, we conducted a novel bibliometric analysis via VOSviewer regarding studies that have investigated the role of inflammasomes in stroke over the past decade to provide a comprehensive view of global research trends. Our bibliometric analysis revealed the increase in the number of articles and changes in contributions of journals, authors, countries and institutions in this field.
The number of articles in a field can reflect the productivity and development of the subject over the years. Our present results showed that the output of publications on the role of inflammasomes in stroke has maintained steady growth from 2008 to 2020. This overall growth trend in the number of related publications indicated that an increasing number of scientists were investigating the role of inflammasomes in stroke. However, a total of more than 400 articles achieved by restricting keywords, are a relatively small volume. In addition, like any other bibliometric analysis, the results have been limited by database used (WOSCC): 30% of the corpus articles identified via PubMed were excluded [8]. Despite this limitation, we believe our findings, to some extent, may contribute to the theoretical study. Furthermore, targeting inflammasomes in treating stroke has potential clinical value [28].
Citations of an article reflect the degree of its dissemination and influence, and sometimes may also reflect its quality. According to the citation analysis (Table 1), there currently is a lack of high-impact articles in this field, in which the most cited article has only 1200 citations and even 6 articles have merely been cited less than 300 times among the top 10. Alternatively, there are many information sources that can not be fully utilized, which is not expected. Therefore, it is necessary to do more work in the integration of knowledge, as the field of “inflammasomes in stroke” continues to develop. Researchers have focused on the role of inflammasomes in stroke for approximately 10 years. During this period, Bergsbaken et al. published a study in NATURE REVIEWS MICROBIOLOGY, and it was the most frequently cited article in our analysis. The authors elucidated a mechanism of action between inflammasomes and pyroptosis. The second most frequently cited article was published in AMERICAN HEART JOURNAL in 2011. The authors found that interleukins were critical mediators of the systemic inflammatory response. Activation of the NLRP3 inflammasome results in enhanced secretion of IL-1β, suggesting that therapeutic interventions targeting the assembly and activity of inflammasomes may have potential clinical benefits [25].
Popular core journals can provide a reliable reference for researchers when searching for documents. Among the journals in which “inflammasomes in stroke” related articles were published, the J NEUROINFLAMM has published the most articles, while STROKE ranks first by citations (Table 2). In terms of publications and citations, the most influential journal was STROKE, which although is the rank of eight in publication, runs first in citation. Moreover, it’s expected to provide researchers with more high-quality articles on “inflammasomes in stroke” related articles. Notably, with the help of the journals rank, researchers can quickly find the suitable journals for their own articles.
We analyzed publications from 37 countries and 551 institutions with the help of a co-authored visual map via VOSviewer. According to the map display (Fig. 3), the Unites States, China, Germany, Australia, and Singapore represented the countries that contributed most to investigating the role of inflammasomes in stroke. Among institutions, UNIV WASHINGTON contributed the most according to institutional citations (Fig. 4). These countries have invested a lot of money, manpower, and material resources in scientific research. Therefore, it is not surprising that they have become the world leaders in this field. Take China as an example: chronic diseases such as stroke, ischemic heart disease and lung cancer have now become the main causes of premature death in the Chinese population. Therefore, China has formulated a series of policies (such as Healthy China 2020 and 2030) and has continuously expanded the health care system to deal with chronic diseases such as stroke. [36] To a certain extent, government policies have greatly supported medical scientific research. Actually, it was found that the number of neuroscience publications in each country were directly proportional to their total per capita health expenditure. [35] At the same time, with the improvement of academics and research funding in recent years, developing countries (e.g., Iran, India) have also begun contributing to this field, and they have tended to exhibited close cooperation with the international community, especially with USA. Meanwhile, our analysis shows China and the United States had the closest cooperation, because there are close academic exchanges between researchers in both countries. Overseas researchers continue to collaborate within the framework of international networks after returning to their home countries.
To identify the authors who contributed the most, we ranked them based on their total numbers of citations. Based on the data extracted from WOSCC, we found that Keane’s citations ranked first, while Fann’s co-citations ranked first. These two authors, who have been recognized by the most researchers in this field, have made outstanding contributions (Table 3). Remarkably, citation is not the only indicator of the academic level, contribution, or influence of researchers, and due to the time effect, recent authors are at a disadvantage in terms of citations regardless of their content and quality. H-index is another measure of scientific influence, but it is reflected the influence of researchers in all areas, not just the in a specific field (e.g. DIETRICH WD in Table 3). Therefore, the ranking of H-index in Table 3 is inconsistent with the ranking of citation. It is necessary to conduct a regular citation analysis of inflammasomes in stroke to update the most authoritative experts in the field. Moreover, co-authorship maps may help researchers learn existing partnerships and confirm potential collaborators.
According to VOSviewer key-word co-occurrence analysis and further literature reading, more information can be obtained shown in Fig. 6. It is not the content of bibliometrics in the traditional sense to collate and summarize the details of these articles. This supplementary work is intended to facilitate the reader's access to the knowledge about stroke in a more effective way. Earlier studies focused on targeting inflammasomes to treat stroke investigated mechanisms of downstream inflammatory cytokines; more recent studies then turned to investigating astrocytes, reactive oxygen species pyroptosis, and immune regulation, as well as other upstream mechanisms. More than 10 inflammasomes have been identified to be associated with stroke. These inflammasomes are expressed in microglia, astrocytes, neurons, and endothelial cells depending on the pathophysiological conditions in stroke.[29] From 2008 to 2020, a growing body of evidence has suggested that activation of inflammasomes triggers neuroinflammation through caspase-1 that further activates various downstream events (e.g. IL-1β, IL-18, IL-6 or TNF-α) and contributes to cell death. Many reviews have described various types of inflammasomes and their mechanisms of activation in stroke. The key factors responsible for activation of inflammasomes are dysregulation of extracellular pH, efflux of Ca2+, failure of K+/Na+ ATPases, mitochondrial dysfunction, and DNA damage [3, 12, 20, 34] Among all known inflammasomes, the most representative is the NLRP3 inflammasome, which is activated in microglia and consists of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and procaspase-1. After stroke, NLRP3 protein is abnormally activated, after which ASC is recruited. ASC then recruits procaspase-1 for its cleavage and activation, which induces the release of proinflammatory cytokines (IL-1β, IL-18, IL-6, and TNF-α) that ultimately increases local inflammation [19] If the harmful effects of inflammatory activation are not offset, the deleterious effects of stroke will become exacerbated. In addition to the NLRP3 inflammasome, stroke is also associated with the NLRP1 inflammatory inflammasome, which is composed of NLRP1, caspase-1, ASC, and X chromosome-linked inhibitor-of-apoptosis protein (XIAP), which is an inhibitor of apoptotic signaling [1, 6, 9, 10, 33] XIAP within the NLRP1 inflammasome may inhibit the activation and processing of IL-1β and IL-18 by inhibiting caspase-1 activity. Additionally, other studies have shown that stroke is also associated with NLRP2 and NLRC4 [17, 23] In view of the accelerated progress in elucidating the mechanisms of inflammasomes, their use as therapeutic targets in stroke represents a promising future clinical application. Among all potential targets, NLRP3 is the most recognized and widely implicated regulator in ischemic stroke. However, the underlying mechanisms of inflammasomes in hemorrhagic stroke have not been fully elucidated.
Unfortunately, no anti-stroke agent directly targeting inflammasomes is currently available. This may be due to insufficient evidence of the role of inflammasomes as important mediators in stroke. In addition, most studies that have investigated the biological activities of natural compounds in inflammatory bodies have been superficial. Hence, it is necessary to further elucidate the precise mechanisms of these compounds in future studies. The pharmacological effects of these natural compounds may be realized by regulating multiple targets and signaling pathways in cerebral ischemia, as opposed to only focusing on a single target. Furthermore, the activity of NLRP3 during different stages of inflammation and the relative role of NLRP3 in neonatal and adult brain inflammation remain unclear. In addition, the relationships between different inflammatory corpuscles and the relationship between inflammation and pyropotic/apoptotic cascades should also be considered. Finally, experiments characterizing the side effects of therapies targeting inflammatory bodies should also be completed.
