Keywords
statin, therapy, neuroinflammation, trend, niche, bibliometric
This article is included in the Neuroinflammation collection.
Neuroinflammase, a key mechanism in neurodegenerative diseases like Alzheimer and Parkinson, is influenced by statin, a lipid-binding protein. Studies show that statin can mitigate the likelihood of developing dementia and Alzheimer’s disease and can also reduce leukocytosis and T-regulatory function. Nevertheless, there is restricted literature on the use of statin in neuroinflammation. The objective of this investigation is to conduct a bibliometric analysis of statin use in neuroinflammation, providing valuable insights into research development and future research questions.
In this work, a literature review methodology is employed to gather data from the Scopus database using the keywords neuroinflammation and statins. Data were analyzed using Biblioshiny and VOSviewer software to produce visualizations and bibliometric maps. We conducted quantitative and qualitative analysis.
The research trend found are Documents by Year, Most Global Cited Document, Most Relevant Sources, Factorial Map Of The Documents With The Highest Contributes, Documents by Author, Most Relevant Affiliations, Documents by Subject Area, Trend Topic, Network Visualization, Overlay visualization of scopus, database using Vosviewer, Density Visualization, Thematic Map, Thematic Evolution, Cluster Analysis, Qualitative Analysis, and Word Cloud.
The study highlights the potential for further research on statins and neuroinflammation, aiming to better understand their role in treating neuroinflammation and enhance the quality of life for patients with neuroinflammatory conditions.
statin, therapy, neuroinflammation, trend, niche, bibliometric
Neuroinflammation serves as a significant secondary mechanism in pathological conditions affecting the nervous system, such as Alzheimer’s disease and Parkinson’s disease. Statins, a class of pharmaceutical agents that reduce lipid levels, have exhibited neuroprotective properties in diverse experimental models of neuroinflammation. Nevertheless, there is a lack of bibliometric research investigating the utilization of statins in relation to neuroinflammation. Statins have broad anti-inflammatory and immunomodulatory effects. Some studies have shown that statin use can reduce the risk of dementia or Alzheimer’s. In addition, other studies show that statins can reduce leukocyte invasion of the brain and increase the proportion of regulatory T cells, which play an important role in modulating the immune response. Therefore, understanding how statins can be used to control neuroinflammation may open new avenues in the treatment of neurological diseases.
Although there is evidence indicating the therapeutic potential of statins in neuroinflammation, there remains a significant lack of research in this area. Most previous research has focused on the effects of statins in experimental models, and little research has been conducted in human patients. Additionally, no bibliometric studies have examined this topic, which means that we do not yet have a comprehensive understanding of research developments in this field.
Bibliometric studies are a very useful tool for understanding research developments in a particular field. By analyzing previous research publications, we can identify research trends, knowledge gaps, and areas that require further research. In the context of statin use in neuroinflammation, bibliometric studies can help us understand how far this topic has been researched and what we still need to know.
Therefore, the aim of this study was to perform a bibliometric analysis of statin use in neuroinflammation. We hope that the results of this study will provide a better picture of research developments in this area and will help formulate research questions for future studies.
In the management of hypercholesterolemia and cardiovascular disease, statins have been extensively employed. Statins primarily function by inhibiting the enzyme HMG-CoA reductase, which is involved in the manufacture of cholesterol. Recent studies have demonstrated that statins possess anti-inflammatory and immunomodulatory properties. Statins have exhibited neuroprotective effects in different experimental models within the framework of neuroinflammation.
Bibliometric research is a research method that uses scientific publication data to describe and analyze the development of a field of science. This research aims to identify and map trends, patterns, and relationships between scientific documents related to certain topics. In this research, the topic chosen was school feeding and stunting. This research uses data from the website www.scopus.com, which is one of the largest and most trusted databases for scientific publications. This research was conducted in March 2024.
To carry out bibliometric research, the steps to follow are as follows:
1. Determine search keywords. In this research, the keywords used are neuroinflammation, and statin. These keywords are entered into the search column on the www.scopus.com site by selecting the topic field (title, abstract, keywords).
2. Filter search results. In this study, Were not filtered.
3. Retrieve the data from the search results. This study involves the retrieval of search result data in three distinct formats, namely:
A search was conducted on the Scopus website using the specified terms, with the understanding that this platform encompasses research that is deemed to possess validity: TITLE – ABS – KEY (neuroinflammation) AND TITLE – ABS – KEY (statin) are the titles of the products that are under consideration. Ninety eight documents were received by us. You then save the document from Scopus in the form of a file with the extension.csv following this step.
Both the Biblioshiny and Vosviewer software packages were utilised in the analysis process.
Documents by year
Based on Figure 1, it appears that there has been an increase in the number of documents, until in 2021 there are 12 documents. The oldest document was in 2002, titled, Interactions of Aβ with endogenous anti-inflammatory agents: A basis for chronic neuroinflammation in Alzheimer’s disease, writings by Janciauskiene, S. Sun, Y.-X. Wright, H.T.1 Meanwhile, the latest document in 2024 is entitled Targeting the CCL2–CCR2 signaling pathway: potential implications of statins beyond cardiovascular diseases, written Gholamalizadeh, H. Ensan, B. Sukhorukov, V.N. Sahebkar, A.2
Most global cited document
Based on Figure 2, the document that received the most citations, with 224 citations, was the document written by Greenwood, J. Walters, C.E. Pryce, G. Baker, D. Adamson, P with title Lovastatin inhibits brain endothelial cell Rho-mediated lymphocyte migration and attenuates experimental autoimmune encephalomyelitis.3 Which was published in the journal The FASEB journal: official publication of the Federation of American Societies for Experimental Biology. In the next position, with 204 citations, is a journal written Alam, A. Hana, Z. Jin, Z. Suen, K.C. Ma, D., in 2018 in the EBioMedicine Journal entitled Surgery, neuroinflammation and cognitive impairment.4 In third place with 141 citations are written documents Xu X, in 2017 in Journal of Neuroinflammation entitled Anti-inflammatory and immunomodulatory mechanisms of atorvastatin in a murine model of traumatic brain injury.5
Most relevant sources
Based on Figure 3, the following are the journals that publish the most important documents. Neuroinflammation is the journal that is ranked first in producing the most documents. The Neuroinflammation Journal is in quartile 1 (Q1) for the Cellular and Molecular Neuroscience and Immunology categories in 2022. The SJR (SCImago Journal Rank) value for the Neuroinflammation Journal in 2022 is 2,439. Neuroinflammation has been indexed in Scopus since 2004. Types of articles published: This journal contains various types of articles such as research and reviews. The main focus of this journal is the interaction of the immune system (especially the innate immune system) with the nervous system. The Journal of Neuroinflammation is published by BioMed Central Ltd. The median time from submission to first editorial decision for all manuscripts was 29 days, and the median time from submission to acceptance was 145 days.
In second place is the journal Brain Research. Brain Research journal was in quartile 2 (Q2) for the Molecular Biology and Developmental Biology category in 2022. Brain Research journal has been indexed in Scopus since 1966. The journal publishes original research articles reporting interesting interdisciplinary investigations of the structure and function of the nervous system for the international community of neuroscientists. In addition, the journal also publishes invited reviews. The Brain Research journal is published by Elsevier.
In third place is CNS Neurological Disorders - Drug Targets. - The last quartile of this journal is Q2. Based on Scopus data, the SJR (SCImago Journal Rank) of this journal is 0.574. This journal has been indexed in Scopus since 2006. The journal publishes thematic issues edited by leaders in the field covering a wide range of current topics from CNS & neurological drug targets. The journal also accepts publication of original research articles, letters, reviews, and drug trial studies. This journal is published by Bentham Science Publishers B.V. Publication times may vary depending on factors such as the complexity of the research and the editorial team’s current workload. Journals typically ask reviewers to submit their reviews within 3-4 weeks.
Factorial map of the documents with the highest contributes
In Figure 4, the following is a factorial map of the documents with the highest contributions based on title. The document that contributes most to cluster 1 is the one written by Gu M in 2021 entitled Neurotoxicity and Underlying Mechanisms of Endogenous Neurotoxins. The document that contributes most to cluster 2 is the one written by Sing I in 2018 entitled Impaired peroxisomal function in the central nervous system with inflammatory disease of experimental autoimmune encephalomyelitis animals and protection by lovastatin treatment.
Documents by author
Based on Figure 5, the three most frequent authors each with three documents are as follows: Adamson, P with the title of the article: Pharmacological targeting of ICAM-1 signaling in brain endothelial cells: Potential for treating neuroinflammation,6 How do statins control neuroinflammation?,7 Lovastatin inhibits brain endothelial cell Rhomediated lymphocyte migration and attenuates experimental autoimmune encephalomyelitis.3
Greenwood, J with the title: Pharmacological targeting of ICAM-1 signaling in brain endothelial cells: Potential for treating neuroinflammation,6 How do statins control neuroinflammation?,7 Lovastatin inhibits brain endothelial cell Rhomediated lymphocyte migration and attenuates experimental autoimmune encephalomyelitis.3
Prediger, R.D. with the title of the article: Atorvastatin Prevents Early Oxidative Events and Modulates Inflammatory Mediators in the Striatum Following Intranasal 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) Administration in Rats,8 Succinobucol, a Non-Statin Hypocholesterolemic Drug, Prevents Premotor Symptoms and Nigrostriatal Neurodegeneration in an Experimental Model of Parkinson’s Disease,9 Atorvastatin improves cognitive, emotional and motor impairments induced by intranasal 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration in rats, an experimental model of Parkinson’s disease.10
Most relevant affiliations
Based on Figures 6, 7, affiliates produce the most documents Medical University of South Carolina with 4 documents and further College of Medicine, Universidade de São Paulo, UCL Institute of Ophthalmology, Imperial College London, Universidade Federal de Santa Catarina, University College London and Fundacao Oswaldo Cruz with 3 documents each.
Documents by subject area
Trend topic
Based on Figure 8, trend topics in 2021 are related to the keyword hemorrhage.
Network visualization
Based on Figure 9, it can be seen that the areas studied are still not related to other areas that are divided into edges. That’s the field: rats,wistar, neuroprotective agent, protein bax, maze test, treatment duration, in vivo study, cell proliferation, pitavastatin, human cell, cytology, autacoid, mevalonic acid, central nervous system, enzyme inhibition, apolipoprotein e, disease course, Alzheimer disease, nonsteroid, anti inflammatory ag, risk factor, brain blood flow, placebo, gelatinase b, major clinical study, treatment outcome, caspase 3.
Overlay visualization of scopus, database using Vosviewer
Based on Figure 10, in the overlay visualization, it appears that the keywords that have been researched a lot approaching 2018 are the part colored yellow, namely: sepsis, complication, cognitive defect, protein blood level, hippocampus, male, brain haemorrhage, nervous system inflammation, animal, statin, pathophysiology, glia cell and metabolism.
Density visualization
Based on Figure 11, in the visual circulation density, it appears that the part that is already saturated with research is yellow, while the part that is not yet saturated is slightly yellow and dominantly green, namely keywords.: protein bax, neuroprotective agent, rats,wistar, neuroprotective agents, caspase 3, complication, mase test, treatment duration, mice, inbred c57bl, c57bl mouse, gene expression, cytology, human cell, immunology, encephalomyelitis, autoimmune, cell proliferation, experimental autoimmune enceph, allergic encephalyelitis, mevalonic acid, pitavastatin, enzyme inhibiton, central nervous system, mevalonic acid, hydroxymethylglutaril ceoenzyme, apolipopprotein e, disease course, alzheimer’s disease, amyloid precursor protein, nonsteroid antiinfllammatory ag, risk factor, pathogenesis, risk factors, pathophysiology, brain blood flow, placebo, low drug dose, gelatinase b, major clinical study, c reactive protein, encephalitis, macrophage, glia cell, mortality, brain ischemia, brain haemorrhage, treatment outcome, blood-brain barrier, and cognitive dysfunction.
Thematic map
Based on Figure 12, based on the thematic map, it appears that the niche themes or themes that are still little researched and have just emerged are the keywords cells, pathway and anti-inflammatory, drug and treatment. The themes that are already saturated and are starting to be abandoned by researchers are themes with the keywords atorvastatin, cognitive, rat, apart from that are experimental, autoimmune, encephalomyelitis, and the themes neuroinflammation, potential, hemorrhage.
Thematic evolution
Based on Figure 13, thematic evolution in 2002-2018 are the keywords delirium, disease, statins, atorvastatin, experimental and model. The theme then changed in 2019-2024 to autoimmune, disease, statins, neuroinflammation, atorvastatin, simvastatin, mode, drug.
Cluster analysis
2 The result of cluster analysis [See extended data92] [See extended data92] [See extended data92]
From 2 5 clusters based on keywords. [See extended data92]
Cluster 1, dominated by Hydroxymethylglutaryl coenzyme a reductase inhibitor drugs, Human, Humans.
Cluster 2, dominated by Nonhuman, Article, Animals.
Cluster 3, dominated by Nervous system inflammation, Neuroinflammation, Microglia.
Cluster 4, dominated by Animal, Metabolism, Male.
Cluster 5, dominated by Inflammation, Atorvastatin, Anti-inflammatory activity.
Diseases for which statins are applied:
4. Dyskinesia26
6. Aneurysmal subarachnoid haemorrhage34
8. Sars-CoV-237
10. Autoimmune diseases, rheumatoid arthritis, and inflammatory bowel diseases
13. Huntington’s Disease54
15. Sepsis57
18. Myasthenia gravis62
22. Scrapie-infected mice75
23. Inflammatory conditions76
24. Restore morphine’s antinociceptive effect, inhibit astrocyte activation, and reduce TNFα and IL-1β expression77
25. Antioxidant, anti-inflammatory, and anti-apoptotic properties, contributing to their clinical efficacy in treating neurological disorders78
Word cloud
Based on Figure 14, word cloud shows that the dominant word in the document is the word children and what follows is statins, disease, atorvastatin and alzheimers.
This bibliometric study shows that research on statins as neuroinflammatory therapies has advanced rapidly in recent years. However, there are still some areas that have not been widely researched and are emerging, such as cells, pathways, anti-inflammatories, drugs, and treatments. These themes show great potential for further research. For example, research on cells and pathways can help us understand the mechanisms underlying the anti-inflammatory effects of statins. Additionally, research on drugs and treatments can help us develop more effective treatment strategies.
On the other hand, some themes seem to have become saturated and are starting to be abandoned by researchers. These include atorvastatin, cognitive, mouse, experimental, autoimmune, encephalomyelitis, neuroinflammatory, potential, and hemorrhage. Although these themes have been widely researched, they still have importance. For example, research on atorvastatin has provided valuable insight into the neuroprotective effects of statins. Additionally, research on neuroinflammation and bleeding potential has helped us understand the pathogenesis of various neurological conditions.
However, the research focus appears to be shifting towards new themes. This may reflect changes in our understanding of neuroinflammation and the role of statins in its treatment. One of the important findings of this study is that research on statins and neuroinflammation is very mixed. It covers a wide range of fields, from cellular biology to clinical pharmacology. Additionally, this study also shows that research on statins and neuroinflammation has been conducted throughout the world. This reflects the importance of this topic in global medical research.
However, there are still several challenges to be faced. For example, although research on cells and pathways has increased, there is still much we need to know about the mechanisms underlying the anti-inflammatory effects of statins. Additionally, although research on drugs and treatments has progressed, there is still a need for larger and better-designed clinical studies. However, despite these challenges, the results of this study show that there are many opportunities for further research. By focusing on new themes and addressing existing challenges, we can hope to make significant progress in research on statins and neuroinflammation.
Overall, this study provides a comprehensive overview of current research on statins and neuroinflammation. By identifying new themes and highlighting under-researched areas, this study can help determine future research directions. However, it is important to remember that bibliometric studies like this have limitations. For example, they depend on the availability of publications and the quality of their indexation. Therefore, the results of this study should be interpreted with caution.
Nonetheless, this study shows that research on statins and neuroinflammation is an active and growing field. By continuing to monitor developments in this field, we can hope to better understand the role of statins in the treatment of neuroinflammation. Finally, further research is needed to fully understand the potential of statins as neuroinflammatory therapies. By focusing on new themes and exploring under-researched areas, we can hope to make significant progress in this research.
In conclusion, this study suggests that there are many opportunities for further research on statins and neuroinflammation. By tapping into new themes and exploring under-researched areas, we can hope to better understand the role of statins in the treatment of neuroinflammation and, ultimately, improve the quality of life for patients with neuroinflammatory conditions.
AYS conducts research, gathers data, performs statistical analysis, and produces discussions and conclusions, RV and DAYS editing.
Figshare: Statins as Neuroinflammatory Therapy, Bibliometric Study, https://doi.org/10.6084/m9.figshare.26002228.v5. 92
The project contains the following underlying data:
• BIBLIOMETRIC SCOPUS Statin as Neuroinflammatory Therapy, Bibliometric Study (ARTICLE).csv (Data (.csv) from www.scopus.com for bibliometric research the effect of statin as neuroinflammatory therapy).
Data are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC BY 4.0 Public domain dedication).
Figshare: Statins as Neuroinflammatory Therapy, Bibliometric Study, https://doi.org/10.6084/m9.figshare.26002228.v5. 92
The project contains the following extended data
Data are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC BY 4.0 Public domain dedication).
Figshare: Statins as Neuroinflammatory Therapy, Bibliometric Study, https://doi.org/10.6084/m9.figshare.26002438.v2. 93
The project contains the following data:
Data are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC BY 4.0 Public domain dedication).
VOSviewer software is an open-access tool that can be used as a cost-effective method for any scientometric analysis. 94
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