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Chronic silencing of subsets of cortical layer 5 pyramidal neurons has a long-term influence on the laminar distribution of parvalbumin interneurons and the perineuronal nets.
Neural networks are established throughout cortical development, which require the right ratios of glutamatergic and GABAergic neurons. Developmental disturbances in pyramidal neuron number and function can impede the development of GABAergic neurons, which can have long-lasting consequences on inhibitory networks. However, the role of deep-layer pyramidal neurons in instructing the development and distribution of GABAergic neurons is still unclear. To unravel the role of deep-layer pyramidal neuron activity in orchestrating the spatial and laminar distribution of parvalbumin neurons, we selectively manipulated subsets of layer 5 projection neurons. By deleting Snap25 selectively from Rbp4-Cre + pyramidal neurons, we abolished regulated vesicle release from subsets of cortical layer 5 projection neurons. Our findings revealed that chronically silencing subsets of layer 5 projection neurons did not change the number and distribution of parvalbumin neurons in the developing brain. However, it did have a long-term impact on the laminar distribution of parvalbumin neurons and their perineuronal nets in the adult primary motor and somatosensory cortices. The laminar positioning of parvalbumin neurons was altered in layer 4 of the primary somatosensory cortex in the adult Snap25 cKO mice. We discovered that the absence of layer 5 activity only had a transient effect on the soma morphology of striatal PV neurons during the third week of postnatal development. We also showed that the relationship between parvalbumin neurons and the perineuronal nets varied across different cortical layers and regions; therefore, their relationship is far more complex than previously described. The current study will help us better understand the bidirectional interaction between deep-layer pyramidal cells and GABAergic neurons, as well as the long-term impact of interrupting pyramidal neuron activity on inhibitory network formation.
Attentional modulation of secondary somatosensory and visual thalamus of mice
Each sensory modality has its own primary and secondary thalamic nuclei. While the primary thalamic nuclei are well understood to relay sensory information from the periphery to the cortex, the role of secondary sensory nuclei is elusive. We trained head-fixed mice to attend to one sensory modality while ignoring a second modality, namely to attend to touch and ignore vision, or vice versa. Arrays were used to record simultaneously from the secondary somatosensory thalamus (POm) and secondary visual thalamus (LP). In mice trained to respond to tactile stimuli and ignore visual stimuli, POm was robustly activated by touch and largely unresponsive to visual stimuli. A different pattern was observed when mice were trained to respond to visual stimuli and ignore touch, with POm now more robustly activated during visual trials. This POm activity was not explained by differences in movements (i.e. whisking, licking, pupil dilation) resulting from the two tasks. Post hoc histological reconstruction of array tracks through POm revealed that subregions varied in their degree of plasticity. LP exhibited similar phenomena. We conclude that behavioral training reshapes activity in secondary thalamic nuclei. Secondary nuclei respond to the same behaviorally relevant, reward-predicting stimuli regardless of stimulus modality.
A KLF2-BMPER-Smad1/5 checkpoint regulates high fluid shear stress-mediated artery remodeling.
Vascular remodeling to match arterial diameter to tissue requirements commonly fails in ischemic disease. Endothelial cells sense fluid shear stress (FSS) from blood flow to maintain FSS within a narrow range in healthy vessels. Thus, high FSS induces vessel outward remodeling, but mechanisms are poorly understood. We previously reported that Smad1/5 is maximally activated at physiological FSS. Smad1/5 limits Akt activation, suggesting that inhibiting Smad1/5 may facilitate outward remodeling. Here we report that high FSS suppresses Smad1/5 by elevating KLF2, which induces the bone morphogenetic protein (BMP) pathway inhibitor, BMP-binding endothelial regulator (BMPER), thereby de-inhibiting Akt. In mice, surgically induced high FSS elevated BMPER expression, inactivated Smad1/5 and induced vessel outward remodeling. Endothelial BMPER deletion impaired blood flow recovery and vascular remodeling. Blocking endothelial cell Smad1/5 activation with BMP9/10 blocking antibodies improved vascular remodeling in mouse models of type 1 and type 2 diabetes. Suppression of Smad1/5 is thus a potential therapeutic approach for ischemic disease.
Evaluation of an integrated variable flip angle protocol to estimate coil B1 for hyperpolarized MRI.
PURPOSE: The purpose of this work is to validate a simple and versatile integrated variable flip angle (VFA) method for mapping B1 in hyperpolarized MRI, which can be used to correct signal variations due to coil inhomogeneity. THEORY AND METHODS: Simulations were run to assess performance of the VFA B1 mapping method compared to the currently used constant flip angle (CFA) approach. Simulation results were used to inform the design of VFA sequences, validated in four volunteers for hyperpolarized xenon-129 imaging of the lungs and another four volunteers for hyperpolarized carbon-13 imaging of the human brain. B1 maps obtained were used to correct transmit and receive inhomogeneity in the images. RESULTS: Simulations showed improved performance of the VFA approach over the CFA approach with reduced sensitivity to T1. For xenon-129, the B1 maps accurately reflected the variation of signal depolarization, but in some cases could not be used to correct for coil receive inhomogeneity due to a lack of transmit-receive reciprocity resulting from suboptimal coil positioning. For carbon-13, the B1 maps showed good agreement with a separately acquired B1 map of a phantom and were effectively used to correct coil-induced signal inhomogeneity. CONCLUSION: A simple, versatile, and effective VFA B1 mapping method was implemented and evaluated. Inclusion of the B1 mapping method in hyperpolarized imaging studies can enable more robust signal quantification.
Care and three-year outcomes of children with Benign Epilepsy with Centro-Temporal Spikes in England.
PURPOSE: Benign Epilepsy with Centro-Temporal Spikes (BECTS) is a pediatric epilepsy with typically good seizure control. Although BECTS may increase patients' risk of developing neurological comorbidities, their clinical care and short-term outcomes are poorly quantified. METHODS: We retrospectively assessed adherence to National Institute for Health and Care Excellence (NICE) guidelines relating to specialist referral, electroencephalogram (EEG) conduct and annual review in the care of patients with BECTS, and measured their seizure, neurodevelopmental and learning outcomes at three years post-diagnosis. RESULTS: Across ten centers in England, we identified 124 patients (74 male) diagnosed with BECTS between 2015 and 2017. Patients had a mean age at diagnosis of 8.0 (95% CI = 7.6-8.4) years. 24/95 (25%) patients were seen by a specialist within two weeks of presentation; 59/100 (59%) received an EEG within two weeks of request; and 59/114 (52%) were reviewed annually. At three years post-diagnosis, 32/114 (28%) experienced ongoing seizures; 26/114 (23%) had reported poor school progress; 15/114 (13%) were diagnosed with a neurodevelopmental disorder (six autism spectrum disorder, six attention-deficit/hyperactivity disorder); and 10/114 (8.8%) were diagnosed with a learning difficulty (three processing deficit, three dyslexia). Center-level random effects models estimated neurodevelopmental diagnoses in 9% (95% CI: 2-16%) of patients and learning difficulty diagnoses in 7% (95% CI: 2-12%). CONCLUSIONS: In this multicenter work, we found variable adherence to NICE guidelines in the care of patients with BECTS and identified a notable level of neurological comorbidity. Patients with BECTS may benefit from enhanced cognitive and behavioral assessment and monitoring.
A Geospatial Analysis of the Availability, Distribution, and Accessibility of Neurosurgical Facilities, Workforce, and Infrastructure in Nigeria; and Projection Towards 2050.
OBJECTIVE: There has been a modest but progressive increase in the neurosurgical workforce, training, and service delivery in Nigeria in the last 2 decades. However, these resources are unevenly distributed. This study aimed to quantitatively assess the availability and distribution of neurosurgical resources in Nigeria while projecting the needed workforce capacity up to 2050. METHODS: An online survey of Nigerian neurosurgeons and residents assessed the country's neurosurgical infrastructure, workforce, and resources. The results were analyzed descriptively, and geospatial analysis was used to map their distribution. A projection model was fitted to predict workforce targets for 2022-2050. RESULTS: Out of 86 neurosurgery-capable health facilities, 65.1% were public hospitals, with only 17.4% accredited for residency training. Dedicated hospital beds and operating rooms for neurosurgery make up only 4.0% and 15.4% of the total, respectively. The population disease burden is estimated at 50.2 per 100,000, while the operative coverage was 153.2 cases per neurosurgeon. There are currently 132 neurosurgeons and 114 neurosurgery residents for a population of 218 million (ratio 1:1.65 million). There is an annual growth rate of 8.3%, resulting in a projected deficit of 1113 neurosurgeons by 2030 and 1104 by 2050. Timely access to neurosurgical care ranges from 21.6% to 86.7% of the population within different timeframes. CONCLUSIONS: Collaborative interventions are needed to address gaps in Nigeria's neurosurgical capacity. Investments in training, infrastructure, and funding are necessary for sustainable development and optimized outcomes.
Assessing the Neurosurgical Capacity in Nigeria Using the Modified Neuro-PIPES Tool.
BACKGROUND: Like many low- and-middle-income countries in Africa, documented assessment of the neurosurgical workforce, equipment, infrastructure, and scope of service delivery in Nigeria is lacking. This study aimed to assess the capacity for the delivery of neurosurgical services in Nigeria. METHODS: An 83-question survey was disseminated to neurosurgeons and residents in Nigeria. We report the findings from the capacity assessment section of the survey, which used the modified neurological-PIPES (personnel, infrastructure, procedures, equipment, and supplies) (MN-PIPES) tool to evaluate the availability of neurosurgical personnel, infrastructure, procedures, equipment, and supplies. A comparative analysis was done using the domain and total MN-PIPES scores and MN-PIPES index. RESULTS: The national average MN-PIPES score and index were 176.4 and 9.8, respectively. Overall, the southwest and northwest regions had the highest scores and frequently had high subscores. The survey respondents reported that the main challenges impeding neurosurgery service delivery were a lack of adjunctive supplies (75.2%), a dearth of diagnostic and interventional equipment (72.4%), and an absence of a dedicated intensive care unit (72.4%). CONCLUSIONS: The availability of workforce, infrastructure, equipment, and supplies needed to provide optimal neurosurgical care is uneven in many institutions in Nigeria. Although major strides have been made in recent years, targeted collaborative interventions at local, national, regional, and international levels will further improve neurosurgical service delivery in Nigeria and will have positive ripple effects on the rest of the healthcare system.
Epidemiological Burden of Neurotrauma in Nigeria: A Systematic Review and Pooled Analysis of 45,763 Patients.
OBJECTIVE: Neurotrauma is a significant cause of morbidity and mortality in Nigeria. We conducted this systematic review to generate nationally generalizable reference data for the country. METHODS: Four research databases and gray literature sources were electronically searched. Risk of bias was assessed using the Risk of Bias in Non-Randomized Studies of Interventions and Cochrane's risk of bias tools. Descriptive analysis, narrative synthesis, and statistical analysis (via paired t-tests and χ2 independence tests) were performed on relevant article metrics (α = 0.05). RESULTS: We identified a cohort of 45,763 patients from 254 articles. The overall risk of bias was moderate to high. Most articles employed retrospective cohort study designs (37.4%) and were published during the last 2 decades (81.89%). The cohort's average age was 32.5 years (standard deviation, 20.2) with a gender split of ∼3 males per female. Almost 90% of subjects were diagnosed with traumatic brain injury, with road traffic accidents (68.6%) being the greatest cause. Altered consciousness (48.4%) was the most commonly reported clinical feature. Computed tomography (53.5%) was the most commonly used imaging modality, with skull (25.7%) and vertebral fracture (14.1%) being the most common radiological findings for traumatic brain injury and traumatic spinal injury, respectively. Two-thirds of patients were treated nonoperatively. Outcomes were favorable in 63.7% of traumatic brain injury patients, but in only 20.9% of traumatic spinal injury patients. Pressure sores, infection, and motor deficits were the most commonly reported complications in the latter. CONCLUSIONS: This systematic review and pooled analysis demonstrate the significant burden of neurotrauma across Nigeria.
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.
The Epidemiological Burden of Neurovascular Pathology in Nigeria: A Systematic Review and Pooled Patient-Level Analysis.
OBJECTIVE: Vascular neurosurgery has developed significantly in Nigeria, but its burden and challenges remain unclear. This study systematically reviewed vascular neurosurgical literature from Nigeria. METHODS: Four research databases and gray literature sources were searched from 1962-2021. ROBINS-I tool was used to assess risk of bias. Descriptive, narrative, and statistical analyses were conducted on all variables. Where appropriate, paired t-tests and Chi-squared independence tests were used (α = 0.05). RESULTS: 56 articles were included and 3203 patients pooled for analysis. Risk of bias was moderate-high. Most articles were published over the last 20 years with retrospective cohort studies and case reports being the most common study designs. The cohort had a relatively even gender split and an average age of 49 years (±22). Cerebrovascular accidents accounted for over 85% of diagnoses, with most etiologies being traumatic. Headache and motor deficit were the most prevalent clinical features. X-ray and carotid angiography were the most commonly reported imaging modalities, closely followed by computed tomography (CT) and CT angiography. The top two radiological diagnoses were ischemic cerebrovascular disease and intracerebral hematoma. Aneurysmal clipping and hematoma evacuation were the most commonly reported treatment modalities. Outcome at last follow-up was favorable in 48%. The mortality rate was 6%. Post-treatment complications included chest infection and rebleeding. CONCLUSIONS: This study illustrates the epidemiological burden of neurovascular pathology (based on the available data in published literature) in Nigeria, and raises awareness amongst service providers and researchers of the attendant challenges and epochal trends seen within vascular neurosurgery in Nigeria.
The Epidemiology of Spinal Neurosurgery in Nigeria: A Systematic Review and Patient-Level Analysis.
OBJECTIVE: Spinal pathologies are prevalent in Nigeria, though epidemiological data remains sparse. This systematic review used pooled patient-level data from across the country to generate a standardized epidemiological reference. METHODS: Four research databases and gray literature sources were searched. Risk of bias assessment was conducted using Risk of Bias in Non-Randomised Studies - of Interventions and Cochrane's risk of bias tool. We descriptively analyzed all article metrics and statistically analyzed relevant data variables via paired t-test and χ2 independence tests (α = 0.05). RESULTS: One hundred twenty-seven articles, comprising a patient cohort of 8425 patients, were analyzed. Most were retrospective cohort studies (46.5%) and case reports/series (31.5%), with an overall moderate-high risk of bias. Most studies were published in the last 20 years. Most patients were male (∼2.5 males per female), with an average age of 43.2 years (±16.4). Clinical diagnoses spanned the breadth of spinal neurosurgery. Approximately 45.0% of patients had complete spinal impairment. Pain (41.7%) was the most reported presenting feature. X-ray (45.1%) was the most common investigation used. Intervertebral disc herniation (18.9%) was the most prevalent imaging finding on MRI. Most patients were managed nonoperatively (57.8%), with a favorable outcome in 27.4% of patients. Posttreatment complications included pressure sores, infection, and motor deficits. CONCLUSIONS: This systematic review and pooled analysis provide an epidemiological overview of spinal neurosurgery in Nigeria over the last 60 years and serves as a useful reference to direct future global research in this arena.
Women in Nigerian Neurosurgery: A Cross-Sectional Survey.
BACKGROUND: Although women have made remarkable strides in several medical specialties in Sub-Saharan Africa, their presence and contribution to the development of neurosurgery remain limited. We sought to study the gender differences within Nigerian neurosurgery, identify challenges resulting from these differences, and recommend how African female neurosurgeons can maximize their effects in neurosurgery. METHODS: A structured online survey captured data on neurosurgical infrastructural capacity, workforce, and training from neurosurgical consultants and residents in neurosurgical centers in Nigeria. All the collected data were coded and analyzed. RESULTS: Altogether, 82 neurosurgical consultants and 67 neurosurgical residents from 50 primary medical institutions in Nigeria completed the online survey. Only 8 of the respondents (5.4%) were women, comprising 3 consultants, 2 senior residents, and 3 junior residents. Although 40.2% of the respondents did not believe that being female affected the decision of whether to specialize in neurosurgery, 46.3% believed that being female was a disadvantage. Most did not believe that being female affected admission (57.8%), completion of a neurosurgery residency (58.5%), or life working as a neurosurgeon after graduation (63.4%). The most common challenges women face while navigating through neurosurgery training and practice are erosion of family and social life, lack of female mentors, and lack of a work-life balance. CONCLUSIONS: There is a deficit of both female consultants and trainees among Nigerian neurosurgeons. Identifying female medical students with a strong interest in neurosurgery and providing early mentorship might increase the number of female neurosurgeons.
The Role of International Collaborations in Sustainable Neurosurgical Development in Nigeria.
OBJECTIVE: Despite 6 decades of existence, neurosurgery is still in the developing stages in Nigeria. In this era of collaborative health system capacity-building in low- and middle-income countries, this article reviews past efforts and future prospects for collaborative neurosurgical development in Nigeria. METHODS: A bibliometric review of the Nigerian neurosurgical literature and data from a structured survey of Nigerian neurosurgeons and residents provided details of current local and international collaborations for neurosurgical research, service delivery, training, and capacity building. These were analyzed to provide an overview of the role of collaborations in sustainable neurosurgical development in Nigeria and to recommend approaches to enhance neurosurgical capacity. RESULTS: In 1023 peer-reviewed neurosurgery publications from Nigeria, there were 4618 authors with 3688 from 98 Nigerian institutions and 930 from 296 foreign institutions in 70 countries. While there were significant research collaborations amongst Nigerian institutions, the most common were with institutions in the US, United Kingdom, and Cameroon. From the survey, 62 of 149 respondents (41.6%) from 32 health facilities noted their institution's involvement in capacity-building neurosurgical collaborations. These collaborations involved 22 Nigerian institutions and 13 foreign institutions in 9 countries and were mostly for training and workforce development (78.1%), and research and data management (59.4%). The majority of foreign institutions were from the US and United Kingdom. CONCLUSIONS: Current and previous neurosurgical collaborations have led to sustainable progress in Nigeria. Further local, regional, and international collaborations would enhance the capacity to address the needs and challenges affecting neurosurgery in Nigeria.
The Status of Specialist Neurosurgical Training in Nigeria: A Survey of Practitioners, Trainers, and Trainees.
OBJECTIVE: Despite the well-known neurosurgical workforce deficit in Sub-Saharan Africa, there remains a low number of neurosurgical training programs in Nigeria. This study sought to reassess the current status of specialist neurosurgical training in the country. METHODS: An electronic survey was distributed to all consultant neurosurgeons and neurosurgery residents in Nigeria. Demographic information and questions relating to the content, process, strengths, and challenges of neurosurgical training were explored as part of a broader survey assessing neurosurgical capacity. Descriptive statistics were used for analysis. RESULTS: Respondents identified 15 neurosurgical training centers in Nigeria. All 15 are accredited by the West African College of Surgeons, and 6 by the National Postgraduate Medical College of Nigeria. The average duration of core neurosurgical training was 5 years. Some identified strengths of Nigerian neurosurgical training included learning opportunities provided to residents, recent growth in the neurosurgical training capacity, and satisfaction with training. Challenges included a continued low number of training programs compared to the population density, lack of subspecialty training programs, and inadequate training infrastructure. CONCLUSIONS: Despite the high number of neurosurgery training centers in Nigeria, compared to other West African countries, the programs are still limited in number and capacity. Although this study shows apparent trainee satisfaction with the training process and contents, multiple challenges exist. Efforts at improving training capacity should focus on continuing the development and expansion of current programs, commencing subspecialty training, driving health insurance to improve funding, and increasing available infrastructure for training.
Profile of Pediatric Neurosurgery in Nigeria from 1962 to 2021: A Systematic Review.
OBJECTIVE: This study aims to provide a comprehensive overview of pediatric neurosurgery in Nigeria, since 1962, by assessing epidemiological data, management strategies, and case outcomes. METHODS: A systematic bibliometric review of Nigerian neurosurgical literature was reported with the PRISMA guidelines. The Risk of Bias Assessment Tool was applied to all nonrandomized studies, and a descriptive analysis was performed for all variables. RESULTS: We identified 12,295 pediatric patients from 196 published studies. Most publications (72.4%) occurred in the recent 2 decades, of which 40.3% were observational case reports/series. The patients were predominantly male (57.2%) and aged 0-18 years, with the majority (66.1%) belonging to the 0-5 age range. Most patients (63.4%) presented between 1-12 months. The most common presenting feature was altered consciousness (7.7%), with computed tomography (38.8%) being the most frequently utilized diagnostic imaging modality. The diagnoses with the greatest prevalence (60.2%) were congenital abnormalities such as hydrocephalus and neural tube defects. 57.5% of cases received surgical therapy, with ventriculoperitoneal shunt placement being the most noticeable procedure performed (36.4%). Complications were identified in 9.5% of cases, with a 4.5% death rate. The Glasgow Outcome Score (95.7%) was the primary outcome measure utilized, with positive outcomes reported in 59.3% of cases. CONCLUSIONS: This review provides significant epidemiological data which emphasizes the country's enormous burden of pediatric neurosurgical cases. The findings can help guide clinical decisions as well as future research and policy development.
The Scope, Trends, and Challenges of Neurosurgical Research in Nigeria: A Bibliometric Review.
OBJECTIVE: This study investigates the scope, trends, and challenges of neurosurgical research in Nigeria since inception of the specialty in 1962. METHODS: A bibliometric review of the neurosurgical literature from Nigeria was performed. Variables extracted included year and journal of publication, article topic, article type, research type, study design, article focus area, and limitations. Descriptive and quantitative analyses were performed for all variables. Trends of research publications were described in three periods: pioneering (1962-1981), recession (1982-2001), and resurgent (2002-2021). RESULTS: Of the 1023 included articles, 10.0% were published in the pioneering period, 9.2% in the recession period, and 80.8% in the resurgent period. Papers were predominantly published in World Neurosurgery (4.5%) and Nigerian Journal of Clinical Practice (4.0%). A total of 79.9% of the 4618 authors were from Nigerian institutions; 86.3% of the articles covered clinical research and were mainly focused on service delivery and epidemiology (89.9%). The most prominent topics were traumatic brain injury (25.8%) and central nervous system malignancy (21.4%). Only 4.4% of the publications received funding, mostly from agencies in the United States (31.7%). Barriers to neurosurgical research included lack of clinical databases (18.0%), increasing burden of disease (12.5%), and diagnostic challenges (12.4%). CONCLUSIONS: Neurosurgical research in Nigeria continues to grow due to increased training, workforce, and infrastructural improvements. Addressing the major challenges through establishment of research databases, development of evidence-based management guidelines, and increasing research training, funding and opportunities can increase research capacity in Nigeria.