Global research trends in viral vectors for neuroregeneration: A bibliometric analysis

Nations, geographical areas, and partnerships

China and the United States of America were the primary centers and cooperation hubs involved in this study sector [Figure 2].

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Figure 2:

Displays the countries participating in the research and the collaborations between them.

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Authors

Verhaagen J had the highest number of citations among authors, with 48 papers and a fractionalized citation count of 7.69. He had maintained a consistent pattern of publishing from 1970 until 2024 [Figures 3 and 4]. Wang Y has authored 41 publications and has a fractionalized citation count of 2.68. Zhang Y has contributed 33 articles with a fractionalized citation count of 2.53, suggesting significant engagement in research focused on the use of viral vectors for neuroregeneration. Zhang X’s name appeared in 28 papers and had a citation count of 2.8, which was divided into fractions.

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Figure 3:

Displays the authors of the articles.

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Figure 4:

Trend in the authors’ work.

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Notable findings from Lotka’s law analysis

A total of 5980 authors, accounting for 76.8% of the total, published only one article, making it the largest category. A total of 1342 authors, accounting for 17.2% of the total, published two pieces, making it the second largest category. The distribution of published papers among authors approximately adheres to the inverse square law, where 193 authors publish 3 articles, 94 authors produce 4 articles [Figure 5], and so on. A total of 11 authors have produced 10 or more publications, indicating their high level of productivity. The author with the highest publication rate has published 48 articles, which is significantly higher than the others.

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Figure 5:

Lotka’s law is depicted, where the X-axis represents the number of published articles and the Y-axis represents the metrics.

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Network analysis provided valuable insights

Cluster 2 [Figure 6] is the most extensive, consisting of 50 writers and representing a primary collaborative community. Chen J has the highest betweenness centrality score, indicating that they frequently lie on the shortest path between other nodes in the network. This suggests that Chen J serves as a hub, connecting different parts of the network. Zhang Y and Wang Y have the highest PageRank, indicating that they are highly influential authors who collaborate with other important authors.

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Figure 6:

The network analysis has 62 nodes, with each node representing a distinct author in the subject.

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Key terms

Co-word factorial analysis, as shown in Figure 6, revealed the presence of four distinct clusters of interconnected words. Cluster 1 comprises terms associated with animal models and experimental techniques such as ‘rats,’ ‘mice,’ ‘axotomy,’ ‘genetic vectors,’ and ‘nerve regeneration.’ Cluster 2 is centered around human and mouse models. Cluster 3 exclusively consists of the term “middle-aged,” while cluster 4 exclusively consists of the term “adult”.

The network analysis metrics indicate that broad phrases such as ‘animals,’ ‘people,’ ‘rats,’ and ‘mice’ have the highest betweenness centrality scores. This suggests that these terms play a crucial role in connecting other, more specialized terms. The term ‘Rats’ exhibits the highest proximity centrality, indicating its strong semantic association with other concepts. Animals possess the highest PageRank, indicating that they exert the greatest influence inside the network.

An examination of the document contents, specifically in Figures 7 and 8, revealed a total of 4,228 keywords.

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Figure 7:

Displays a network analysis of terms.

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Figure 8:

Displays the results of the keyword analysis.

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The word ‘Animals’ had the highest frequency, appearing 624 times. This indicates a notable emphasis on animal studies within the scientific body.

The term ‘Humans’ appears 308 times, as shown in the Figure 8.

The terms ‘rats’ and ‘mice’ appear 273 and 242 times, respectively.

The terms ‘animals,’ ‘females,’ and ‘vectors’ have shown an upward trend in their usage within this research field throughout time, as depicted in Figure 9.

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Figure 9:

Word tree diagram.

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Emerging patterns in subjects

The utilization of electron microscopy reached its highest point in the late 1980s to 1990s and has since been progressively dropping [Figure 10]. Gene therapy techniques such as the use of viral vectors and transgenic mice reached their highest level of development in the early 2000s. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and COVID-19-associated terminology have experienced a rapid emergence within the past 5 years. The initial subjects of discussion in the 1990s revolved around fundamental methods such as electron microscopy and molecular biology tools like in situ hybridization. Nerve regeneration became a prominent area of study in the early 2000s, alongside the utilization of model organisms such as rats and mice. Viral vectors gained widespread acceptance in the mid-2000s.

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Figure 10:

Displays the frequency of words over the course of several years.

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Between 2010 and 2015, there was a significant increase in research focused on the mechanisms underlying cell survival and the use of animal models to study diseases. Translational objectives begin to arise. Over the past 5 years, advanced methodologies such as CRISPR gene editing have emerged. The COVID-19 pandemic emerged as a significant focal point beginning in 2020. The main approaches of this study are reflected in high-frequency subjects such as ‘rats,’ ‘mice,’ and ‘gene transfer.’ Recent subjects have a lower frequency of occurrence. The interquartile range indicates the specific period during which each issue exhibited the highest level of activity. Most subjects typically cover a span of 5 to 10 years, which highlights the significant influence of technology in this industry.

The Thematic Map Clusters analysis utilized network analysis to identify 10 clusters based on the phrases found in the published corpus. This has been illustrated in Figure 11. The cluster focused on “nerve regeneration” exhibited the greatest centrality and density. The density of the “animals” cluster was rather low.

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Figure 11:

Displays the pattern or trajectory of various subjects over time.

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The articles authored by Lopez-Leon S and colleagues in 2021 and 2022 explored the enduring consequences of COVID-19 and long-COVID in the pediatric population.

Neurological Conditions: The 2020 paper by Vukusic S and colleagues examines the frequency of progressive multifocal leukoencephalopathy in individuals with multiple sclerosis, shedding light on the continued investigation of severe neurological disorders linked to viral infections. Lu Y and colleagues’ 2020 study explored the use of epigenetic interventions to restore youthful epigenetic information and improve vision through neuroregeneration. The main thematic clusters are “adolescent” and “animals”. Articles authored by Lu Y on epigenetic therapies and by Vukusic S on neurological diseases exhibit elevated pagerank values.

The combined number of citations to these works from 1965 to 2024 is 15,520 [Table 1]. The average number of citations each year is 287, and the average number of citations per paper is 19.8. The average number of authors listed for each work is 4.25. The publication collection has an h-index of 18. There are a total of 18 papers, each of which has acquired a minimum of 18 citations.

Journals

The Journal of Neuroscience is the primary source of articles, accounting for 40 publications. Experimental Neurology has a total of 39 articles, while Neural Regeneration Research has 24 articles. The top 10 sources consist exclusively of renowned neuroscience journals such as The Journal of Neuroscience, Brain, and Glia. The primary literature on the use of viral vectors for neuroregeneration research is primarily published in specialized neuroscience publications [Figures 12 and 13].

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Figure 12:

Displays the results of the investigation on thematic map clusters.

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Figure 13:

Displays the publication trend in journals specifically focused on viruses and neurogeneration.

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Following the top 10, there is an extensive compilation of journals encompassing many biological disciplines such as neuroscience, neurology, gene therapy, virology, immunology, and others. There are a total of 162 distinct journal sources.

The number of articles per source varies significantly, ranging from 1 article for numerous journals to 40 articles for the most prominent source. The emergence of publications in this field commenced in 1994. The level of activity during the 1990s was extremely low, with less than 10 papers each year across all five sources. From 2000 to 2010, there was a consistent and gradual increase in publications, with the number of papers each year rising from 13 to 61. The Journal of Neuroscience and Experimental Neurology experienced the highest level of expansion. The number of publications had a significant increase from 2010 to 2015, approximately doubling from 61 to 117 papers per year. From 2015 to 2024, the publishing rates in the top five journals remained constant at approximately 120 pieces each year.

Most of the increase was focused in The Journal of Neuroscience and Experimental Neurology. Gene Therapy, a niche journal, introduced publications on this topic at a later stage but maintained a relatively small size.

Nations, geographical areas, and partnerships

The bibliometric examination of 776 papers from 1970 to 2024 revealed interesting findings about the study of viruses in neuroregeneration. The Collaboration Network analysis offers a comprehensive view of the interconnections and incorporation of researchers who contribute to publications on virus-induced neuroregeneration. The network metrics measure the level of collaboration within this burgeoning subject. The USA and China demonstrated strong leadership, as seen in other scientific domains.²² It is beneficial that a tropical country with a high prevalence of infection is collaborating with a developed country that specializes in neuroregenerative research, such as the US.

Authors

Verhaagen’s contribution has made a substantial impact in the scientific community, with a wide-ranging influence on the area. Wang’s fractionalized citation count of 2.68 indicates significant contributions to the literature, however with a lower average impact per publication compared to Verhaagen.

The data on Lotka’s law reveals that author productivity in this field adheres to Lotka’s rule, where a small number of authors produce the bulk of publications, while many writers publish only a few papers. This asymmetrical distribution is anticipated in a nascent interdisciplinary domain. The data measures the level of subject knowledge creation that is concentrated among a small group of highly productive authors.

Current issues of interest

The frequent occurrence of the terms ‘animals’ and ‘rats’ highlights the significance of animal models in neuroregeneration research, specifically in comprehending the effects of viruses on neurological well-being.

The findings indicate a significant focus on empirical research utilizing animal models, which demonstrates the field’s dependence on these models to investigate the mechanisms of neuroregeneration and the adverse effects of viruses on the nervous system. Translation and human research are necessary and can be initiated.

In general, the subjects illustrate a progression from fundamental methods to mechanistic investigations to translational research. The emergence of COVID-19 brought about a pressing and immediate change in course. The duration of subjects reflects the swift assimilation of technologies in this dynamic field of study.

The co-word analysis uncovers clear groupings of terms associated with animal models, human research, aging populations, and experimental techniques. The network analysis reveals the comprehensive framework and connections among broad and specific concepts. Rats exhibit notably high centrality, indicating their significance as a preclinical model. However, the translation of scientific knowledge into practical applications may necessitate the use of primate research.

The concept of “Nerve regeneration” was a prominent focus that was closely associated with other subjects. The diffusion of the “animals” theme indicates a wider utilization of animal models in several study fields. Similar to other research fields,²³ recent articles have demonstrated a notable interest in the prolonged consequences of the epidemic.

The subject clusters were mostly centered around the topics of “adolescent” and “animals,” indicating specific areas of inquiry within the broader field of utilizing viral vectors for neuroregeneration. The greater pagerank values of epigenetic therapies indicate their substantial influence in the field.

These findings demonstrate the extensive scope of study on the use of viruses for neuroregeneration, emphasizing important areas of concentration such as the long-term consequences of COVID-19, severe neurological disorders, and novel therapeutic strategies such epigenetic reprogramming.

Citations

The average number of citations each year is 287, whereas the average number of citations per paper is 19.8. This suggests a relatively high level of influence through citations in the field.The average number of authors per manuscript is 4.25. This exemplifies the cooperative essence of neuroscience research. The h-index of the publication collection is 18. Consequently, there are 18 works that have individually garnered a minimum of 18 citations. This indicates a significant number of influential papers in the topic.

The fractionalized citation count offers a measure of an author’s work impact in relation to the number of publications published. It specifically highlights authors whose research has had a substantial influence within the community studying the use of viral vectors for neuroregeneration.

The analysis reveals a significantly elevated citation impact for the application of viral vectors in neuroregeneration research, averaging close to 20 citations per manuscript. The presence of multiple authors and a high h-index underscore the collaborative and influential character of research in this field. The measures measure the increasing impact of this developing discipline in recent decades.

Normalized citation metrics and self-citation adjustment

To better assess research influence beyond raw citation counts, we considered field-weighted citation metrics and excluded self-citations where applicable. The average citation per article in the corpus was 19.8; however, when normalized using the Field-Weighted Citation Impact (FWCI) approach, comparing each article’s citations to the global average for similar documents, the top-cited papers exhibited an FWCI range between 1.5 and 3.8, indicating above-average influence relative to their field and publication year. Notably, publications in The Journal of Neuroscience and Experimental Neurology maintained high normalized impact, reflecting their status as core platforms within the neuroregeneration and virotherapy fields. In evaluating author-level data, fractionalized citation counts were used to account for co-authorship, and self-citations were excluded where data permitted, particularly in assessing the relative influence of highly prolific authors such as Verhaagen J. This adjustment reduced individual citation counts modestly but did not alter overall author rankings, affirming their sustained external impact. These field-adjusted metrics provide a more equitable measure of scholarly influence, correcting for disciplinary citation norms and collaborative publication practices.

Altmetric and uptake insights: Real-world relevance of highly cited studies

While traditional citations offer a snapshot of academic influence, assessing altmetric indicators and translational uptake helps contextualize real-world impact. Although specific altmetric scores (e.g., social media mentions, policy citations) were not uniformly available across the dataset, qualitative analysis of the most highly cited and field-weighted impactful papers revealed strong clinical and translational relevance. For instance, studies by Davidson and Breakefield ²⁴ on viral vectors for CNS gene delivery have been widely cited not only in academic literature but also in clinical trial designs and regulatory white papers, particularly in AAV-based therapies for Parkinson’s and spinal muscular atrophy. Similarly, Humbel et al.²⁵ (2021) on optimizing lentiviral gene transfer has been referenced in technical protocols used by commercial biotech firms involved in gene therapy delivery systems. The recent emphasis on COVID-19-associated neuroregeneration studies¹⁹ has shown rapid citation accumulation and has been frequently mentioned in media outlets and public health forums, reflecting immediate translational curiosity. Collectively, these findings suggest that the most cited papers within the corpus are not only academically robust but also influential in clinical discourse, experimental design, and therapeutic innovation.

Journals

The distribution of journals indicates that the use of viral vectors for neuroregeneration research is a multidisciplinary subject, with articles appearing in several biomedical sub-disciplines [Figure 14].

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Figure 14:

Displays the number of publications published in journals.

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The distribution of the number of articles by source is skewed, as anticipated, with a small number of core journals responsible for publishing most papers, while numerous peripheral journals publish irregularly on this issue.

In general, this source list offers a thorough and detailed summary of the publishing industry, highlighting the importance of neuroscience journals and the interdisciplinary approach to using viral vectors in neuroregeneration research. The abundance of sources emphasizes the widespread distribution of material across several magazines and fields.

In general, the data indicates that the use of viral vectors for neuroregeneration became a separate field of research in the mid-1990s. This field then experienced growth and increased interest during the 2010s. It has now developed into a well-established discipline with consistent publication in specialized journals such as The Journal of Neuroscience. The growth trends emphasize significant times that propelled scientific advancement.

Areas of interest for future research emphasis

AAlthough there has been substantial growth in studies on viruses in neuroregeneration in recent decades, there are still important gaps in understanding that need to be addressed in future studies. Important areas for future research include investigating the specific mechanisms by which viruses enhance the natural regeneration of nerve cells, creating more sophisticated carriers for gene therapy, studying the potential neuroregenerative effects of newly discovered viruses such as COVID-19, and utilizing inflammation caused by viral infections to facilitate the repair of neural tissue.²⁴ Further investigation into the genes responsible for axon regeneration, which are activated by viral infections, could reveal potential targets for therapy that can accelerate the natural pathways of neuroregeneration.²⁶ The ongoing objective is to optimize viral vectors for the purpose of safe and targeted gene delivery, to facilitate precise targeting of neuroregenerative interventions.²⁵ Investigating the long-term effects of COVID-19 on the brain’s ability to change and heal itself is still a topic of ongoing research. This has significant consequences for clinical practice. There is a need for more in-depth research to understand the mechanisms behind modifying neuroinflammation caused by viral triggers in order to enhance neuronal regeneration instead of impeding it.²⁵ By doing thorough empirical research, we can fill these important gaps in knowledge and greatly enhance the practical use of viral biology findings in the field of neuroregenerative medicine.

Expanded clinical context: Alignment with therapeutic development and trials

The trajectory of research on viral vectors for neuroregeneration mirrors broader trends in therapeutic innovation, particularly in gene therapy and neurorestorative medicine. Davidson and Breakefield’s landmark review²⁴ elucidated the early clinical promise of viral vectors, particularly lentiviral and adeno-associated viruses (AAVs), in targeting the CNS for durable gene expression. This foundational work catalyzed subsequent preclinical and early clinical trials aiming to restore neural function in conditions like Parkinson’s disease, spinal cord injuries, and inherited neurodegenerative disorders. More recently, Humbel et al.²⁵ (2021) highlighted efforts to maximize lentiviral vector delivery in CNS tissues, aligning with ongoing translational strategies that emphasize vector optimization for safety, targeting specificity, and minimal immunogenicity. The bibliometric patterns identified in the current review reflect this shift, particularly the post-2010 surge in publications, which coincides with increased investment in regenerative trials and neurogene therapy platforms. Furthermore, the exploration of axon regeneration genes via RNAi screening in C. elegans ²⁶ illustrates the bench-to-bedside trajectory where molecular insights are rapidly translated into novel therapeutic targets. These cumulative efforts not only mark viral vectors as pivotal in experimental therapeutics but also demonstrate a convergence of bibliometric growth and clinical applicability, underscoring the translational maturity of this research frontier.

Future directions: Linking viral mechanisms to regenerative outcomes

A pivotal future direction involves elucidating the specific viral mechanisms that directly contribute to neural regeneration. Viruses possess innate abilities to modulate host gene expression, trigger immune signaling cascades, and induce membrane fusion, features that can be therapeutically harnessed. For example, the mechanism of virus-induced membrane fusion explored by Osorio et al.¹³ (2022) suggests a novel pathway to promote cellular connectivity and synaptic repair. Additionally, certain viral vectors can activate axon regeneration genes, as demonstrated in RNAi-based screenings²⁶ highlighting their role beyond gene delivery as molecular enhancers of regeneration. Emerging research should focus on dissecting how viral entry, replication inhibition, and immunogenic modulation affect neurogenic pathways, with an emphasis on controlled inflammatory responses that could pivot from neurotoxic to neurorestorative outcomes. Mechanistic clarity in these domains will be critical for developing precise, safe, and efficacious viral-based interventions capable of driving structural and functional recovery in CNS disorders.

Advancing precision therapeutics in neuroregeneration

An emerging frontier in viral vector-based neuroregeneration is the development of precision therapeutics, tailored interventions designed to target specific neural circuits, cell types, or genetic profiles. Precision strategies leverage the tropism of viral vectors, enabling delivery of therapeutic genes or regulatory elements to discrete neuronal populations. Recent advancements in vector engineering, including the use of promoter elements and capsid modifications, allow for highly selective gene expression, minimizing off-target effects and systemic toxicity. Moreover, integrating CRISPR-based gene editing with viral delivery systems offers the potential to correct disease-causing mutations at the source, as reflected by the increasing occurrence of CRISPR-related terms in the corpus. These approaches align with a broader shift toward patient-specific or genotype-guided therapies, particularly relevant for complex neurodegenerative diseases like Amyotrophic lateral sclerosis (ALS) and Huntington’s. Future research should aim to combine vector precision, real-time monitoring technologies, and patient-derived models to optimize efficacy and safety. Ultimately, this precision framework could redefine therapeutic standards in neuroregeneration, offering interventions that are not only effective but customized to the molecular and cellular landscape of each patient.

Funding analysis and influence on research priorities

Although the present bibliometric analysis did not include explicit funding metadata, the patterns of research output and collaboration networks imply substantial influence from institutional and national funding bodies, particularly in the United States and China. These countries emerged as central nodes in global research networks, aligning with their heavy investment in neuroscience, virology, and gene therapy initiatives. For instance, the surge in publications post-2010 corresponds temporally with increased funding for translational research and regenerative medicine, such as National Institutes of Health’s Brain Research through Advancing Innovative Neurotechnologies (NIH’s BRAIN) Initiative and China’s National Key R&D Program. The high productivity of prominent authors and institutions, especially in top-tier journals, also suggests a concentration of funding around high-impact centers, enabling sustained work on viral vector development and neural repair. Furthermore, the rapid rise in COVID-19-related neuroregeneration studies since 2020 reflects adaptive shifts in funding priorities toward pandemic-related neuroscience, as seen globally. Thus, while direct grant data was not captured, bibliometric indicators strongly suggest that funding availability and strategic research investments are key drivers of topic emergence, collaborative intensity, and technological innovation in the field of viral vectors for neuroregeneration.

Institutional impact on research development

While author-level contributions were prominent, especially those by Verhaagen J, Wang Y, and Zhang Y, a broader examination reveals significant institutional influence in shaping the landscape of viral vector research for neuroregeneration. The most active and influential contributors are consistently affiliated with major neuroscience and biomedical institutions in the United States, China, and parts of Europe. Institutions such as the Netherlands Institute for Neuroscience (associated with Verhaagen), the Chinese Academy of Sciences, and leading U.S. universities (e.g., Johns Hopkins, Stanford) are repeatedly represented in high-impact publications. Their presence in prolific collaborations and as sources of multi-authored studies suggests centralized hubs of innovation, often benefiting from robust infrastructure, cross-disciplinary labs, and strategic funding. These institutions not only drive publication volume but also steer thematic focus areas, from gene therapy optimization to translational neuroregenerative applications, reflecting their capacity to influence both basic science and clinical research agendas. Thus, beyond individual authorship, institutional ecosystems act as engines of sustained scientific advancement, reinforcing the alignment of institutional prestige, funding access, and global research influence in this field.

This analysis was limited to English-language publications indexed in Scopus and Web of Science, which may under-represent non-English literature from regions with high viral disease burden. Manual screening was performed independently by two authors, with discrepancies resolved through consensus. While AI-assisted screening was not employed in this analysis, future studies may incorporate machine learning tools to enhance reproducibility.