Exploring the evolution of research connectivity and funding in global neurosurgical publications.

BACKGROUND AND OBJECTIVES: There are critical disparities in the neurosurgical care provided around the globe due to challenges in resource allocation, training, and infrastructure. Global neurosurgical collaborations have replaced classical mission trips to address these disparities. However, the development of these collaborations and the impact of research funding on their growth has not yet been systematically studied. In this article, we use a graph theoretical approach to investigate trends in funding and co-authorship between and among authors from high-income countries (HICs) and authors from low- and middle-income countries (LMICs). METHODS: A bibliometric search of the global neurosurgical literature returned 307 articles between 1985 and 2020. A connectivity analysis was conducted to compute the number of co-authorships between HIC-HIC, LMIC-HIC, and LMIC-LMIC authors. The number of connections, summarized as either a global sum of connections or an average number of connections per manuscript, were analyzed in the context of time and funding through parametric statistical tests. RESULTS: An exponential increase in co-authorship collaboration was observed over time, especially after 2015. Notably, LMIC-LMIC collaborations appear to be rising at over twice the rate of other collaboration types. The presence of funding, in general, was associated with increased co-authorship of manuscripts by LMIC and HIC authors together (p = 0.033). A significant majority of the funding associated with LMIC-HIC co-authorships was supplied through charitable organizations and government grants (p = 0.034, p = 0.009, respectively). Most LMIC-LMIC co-authorships had no funding. CONCLUSION: This work shows significant and rapid growth in international neurosurgical partnerships, especially in HIC-LMIC and LMIC-LMIC collaborations. Also, a significant positive relationship exists between research funding and LMIC-HIC co-authorship trends. This work encourages us as a community to continue to expand our translational collaborations with LMIC neurosurgeons and establish funding mechanisms independent of HIC authors.

Epidemiology and Management Trends of Neuro-Oncology in Nigeria: A Systematic Review and Pooled Analysis.

OBJECTIVE: Access to neuro-oncologic care in Nigeria has grown exponentially since the first reported cases in the mid-1960s. In this systematic review and pooled analysis, we characterize the growth of neurosurgical oncology in Nigeria and build a reference paper to direct efforts to expand this field. METHODS: We performed an initial literature search of several article databases and gray literature sources. We included and subsequently screened articles published between 1962 and 2021. Several variables were extracted from each study, including the affiliated hospital, the number of patients treated, patient sex, tumor pathology, the types of imaging modalities used for diagnosis, and the interventions used for each individual. Change in these variables was assessed using Chi-squared independence tests and univariate linear regression when appropriate. RESULTS: A total of 147 studies were identified, corresponding to 5,760 patients. Over 4000 cases were reported in the past 2 decades from 21 different Nigerian institutions. The types of tumors reported have increased over time, with increasingly more patients being evaluated via computed tomography (CT) and magnetic resonance imaging (MRI). There is also a prevalent use of radiotherapy, though chemotherapy remains an underreported treatment modality. CONCLUSIONS: This study highlights key trends regarding the prevalence and management of neuro-oncologic pathologies within Nigeria. Further studies are needed to continue to learn and guide the future growth of this field in Nigeria.

Peripheral nervous system glia in support of metabolic tissue functions.

The peripheral nervous system (PNS) relays information between organs and tissues and the brain and spine to maintain homeostasis, regulate tissue functions, and respond to interoceptive and exteroceptive signals. Glial cells perform support roles to maintain nerve function, plasticity, and survival. The glia of the central nervous system (CNS) are well characterized, but PNS glia (PNSG) populations, particularly tissue-specific subtypes, are underexplored. PNSG are found in large nerves (such as the sciatic), the ganglia, and the tissues themselves, and can crosstalk with a range of cell types in addition to neurons. PNSG are also subject to phenotypic changes in response to signals from their local tissue environment, including metabolic changes. These topics and the importance of PNSG in metabolically active tissues, such as adipose, muscle, heart, and lymphatic tissues, are outlined in this review.

Schwann cells contribute to demyelinating diabetic neuropathy and nerve terminal structures in white adipose tissue.

Peripheral neuropathy, which can include axonal degeneration and/or demyelination, impacts adipose tissues with obesity, diabetes, and aging. However, the presence of demyelinating neuropathy had not yet been explored in adipose. Both demyelinating neuropathies and axonopathies implicate Schwann cells (SCs), a glial support cell that myelinates axons and contributes to nerve regeneration after injury. We performed a comprehensive assessment of SCs and myelination patterns of subcutaneous white adipose tissue (scWAT) nerves, and changes across altered energy balance states. We found that mouse scWAT contains both myelinated and unmyelinated nerves and is populated by SCs, including SCs that were associated with synaptic vesicle-containing nerve terminals. BTBR ob/ob mice, a model of diabetic peripheral neuropathy, exhibited small fiber demyelinating neuropathy and alterations in SC marker gene expression in adipose that were similar to obese human adipose. These data indicate that adipose SCs regulate the plasticity of tissue nerves and become dysregulated in diabetes.

Age-related changes to adipose tissue and peripheral neuropathy in genetically diverse HET3 mice differ by sex and are not mitigated by rapamycin longevity treatment.

Neural communication between the brain and adipose tissues regulates energy expenditure and metabolism through modulation of adipose tissue functions. We have recently demonstrated that under pathophysiological conditions (obesity, diabetes, and aging), total subcutaneous white adipose tissue (scWAT) innervation is decreased ('adipose neuropathy'). With advanced age in the C57BL/6J mouse, small fiber peripheral nerve endings in adipose tissue die back, resulting in reduced contact with adipose-resident blood vessels and other cells. This vascular neuropathy and parenchymal neuropathy together likely pose a physiological challenge for tissue function. In the current work, we used the genetically diverse HET3 mouse model to investigate the incidence of peripheral neuropathy and adipose tissue dysregulation across several ages in both male and female mice. We also investigated the anti-aging treatment rapamycin, an mTOR inhibitor, as a means to prevent or reduce adipose neuropathy. We found that HET3 mice displayed a reduced neuropathy phenotype compared to inbred C56BL/6 J mice, indicating genetic contributions to this aging phenotype. Compared to female HET3 mice, male HET3 mice had worse neuropathic phenotypes by 62 weeks of age. Female HET3 mice appeared to have increased protection from neuropathy until advanced age (126 weeks), after reproductive senescence. We found that rapamycin overall had little impact on neuropathy measures, and actually worsened adipose tissue inflammation and fibrosis. Despite its success as a longevity treatment in mice, higher doses and longer delivery paradigms for rapamycin may lead to a disconnect between life span and beneficial health outcomes.

The Scope, Growth, and Inequities of the Global Neurosurgery Literature: A Bibliometric Analysis.

BACKGROUND: Here, we evaluate the evolution and growth of global neurosurgery publications over time, further focusing on the contributions and impact of authors in low- and middle-income countries (LMICs). METHODS: In this systematic bibliometric analysis, we conducted a two-stage blinded screening process of global neurosurgery publications from 5 databases from inception through July 2021. Articles involving multi-national/multi-institutional research collaborations, detailing any area of global neurosurgery collaboration, or influencing global neurosurgery practice were included. Statistical hypothesis testing was conducted to analyze trends and hypotheses of LMIC authorship contributions. RESULTS: The number of global neurosurgery publications has soared in the last decade. Overall, authors from HIC countries were most commonly from the US (41.1%), Canada (4.0%), and the UK (3.9%), while authors from LMIC countries were most commonly from Uganda (4.2%), Tanzania (2.6%), Cameroon (1.8%), and India (1.8%). Over a quarter (28%) of publications had no LMIC authors, while only 11% had 3 or more LMIC authors. The proportion of LMIC authors (LMIC-R) was not correlated with the citation rate of individual articles or with the year of publication, and a positive trend emerged when the LMIC-R of top-publishing LMICs was individually examined and compared to the year of publication. CONCLUSIONS: Despite recent growth, the number of global neurosurgery publications arising from LMICs pales in comparison to those from HICs. Collaborative efforts between certain HICs and LMICs have likely contributed to the observed increase in LMIC author independence over time.

Neuropathy and neural plasticity in the subcutaneous white adipose depot.

The difficulty in obtaining as well as maintaining weight loss, together with the impairment of metabolic control in conditions like diabetes and cardiovascular disease, may represent pathological situations of inadequate neural communication between the brain and peripheral organs and tissues. Innervation of adipose tissues by peripheral nerves provides a means of communication between the master metabolic regulator in the brain (chiefly the hypothalamus), and energy-expending and energy-storing cells in the body (primarily adipocytes). Although chemical and surgical denervation studies have clearly demonstrated how crucial adipose tissue neural innervation is for maintaining proper metabolic health, we have uncovered that adipose tissue becomes neuropathic (ie: reduction in neurites) in various conditions of metabolic dysregulation. Here, utilizing both human and mouse adipose tissues, we present evidence of adipose tissue neuropathy, or loss of proper innervation, under pathophysiological conditions such as obesity, diabetes, and aging, all of which are concomitant with insult to the adipose organ as well as metabolic dysfunction. Neuropathy is indicated by loss of nerve fiber protein expression, reduction in synaptic markers, and lower neurotrophic factor expression in adipose tissue. Aging-related adipose neuropathy particularly results in loss of innervation around the tissue vasculature, which cannot be reversed by exercise. Together with indications of neuropathy in muscle and bone, these findings underscore that peripheral neuropathy is not restricted to classic tissues like the skin of distal extremities, and that loss of innervation to adipose may trigger or exacerbate metabolic diseases. In addition, we have demonstrated stimulation of adipose tissue neural plasticity with cold exposure, which may ameliorate adipose neuropathy and be a potential therapeutic option to re-innervate adipose and restore metabolic health.