The Top 100 Cited Articles on Cervical Disc Arthroplasty: A Bibliometric Analysis.

STUDY DESIGN: Bibliometric analysis. OBJECTIVE: Cervical disc arthroplasty (CDA) has emerged as an effective surgical intervention for degenerative cervical disc disease with potential advantages over traditional cervical fusion. This bibliometric analysis aimed to assess the current state of research on CDA by analyzing the relevant literature using bibliometric indicators. SUMMARY OF BACKGROUND DATA: Web of Science Core Collection. METHODS: A comprehensive search was conducted using the Web of Science database, for articles related to CDA published in the last 19 years. The top 100 articles were reviewed using bibliometric analysis. Publication trends, citation patterns, authorship, and collaboration networks were analyzed using VOSviewer and the Bibliometrix package in RStudio. RESULTS: The results revealed a significant increase in the number of publications related to CDA over the past 2 decades, with most of the articles being published in orthopedic and spine surgery journals. The most frequently cited articles were related to clinical outcomes, complications, and biomechanical studies of CDA. Co-authorship analysis identified influential authors and collaborative networks, highlighting the multidisciplinary nature of CDA research involving neurosurgeons, orthopedic surgeons, and engineers. Overall, this bibliometric analysis provides a comprehensive overview of the current state of research on CDA, highlighting the key research themes, influential authors, and collaborative networks in the field. CONCLUSION: These findings can serve as a guide for researchers, clinicians, and policymakers to identify knowledge gaps, research trends, and future directions in the field of CDA.

Da Vinci Meets Globus Excelsius GPS: A Totally Robotic Minimally Invasive Anterior and Posterior Lumbar Fusion.

BACKGROUND: Minimally invasive approaches to the spine via anterior and posterior approaches have been increasing in popularity, culminating in the development of robot-assisted spinal fusions. The da Vinci surgical robot has been used for anterior lumbar interbody fusion (ALIF), with promising results. Similarly, multiple spinal robots have been developed to assist placement of posterior pedicle screws. However, no previous cases have reported on using robots for both anterior and posterior fixation in a single surgery. We present a technical note on the first reported case of a totally robotic minimally invasive anterior and posterior lumbar fusion and instrumentation. METHODS: A 65-year-old man with chronic low back pain and left greater than right lower extremity radiculopathy was found to have grade 1 spondylolisthesis at L5/S1 that worsened on standing upright. He underwent ALIF using a da Vinci robotic approach, followed by percutaneous posterior instrumented fusion with the Globus Excelsius GPS robot. RESULTS: The patient did well postoperatively, with improvement of back and leg pain at 3 months follow-up. Radiography confirmed appropriate placement of the interbody cage and pedicle screws. CONCLUSIONS: All-robotic placement of both ALIF and posterior lumbar pedicle fixation may be safe, feasible, and efficacious.

The 100 Top-Cited Articles on Robotic Neurosurgery: A Bibliometric Analysis.

BACKGROUND: Robotic neurosurgery is a rapidly advancing field with numerous applications in various subspecialties, including spine, functional, skull base, and cerebrovascular. This study aims to provide a comprehensive analysis of the most-cited articles on robotic neurosurgery. METHODS: The Web of Science database was used to collect data, and bibliometric analysis was performed using VOSviewer and RStudio. Network analysis techniques such as co-occurrence, coauthorship, bibliographic coupling, and thematic mapping analyses were used to identify the top 100 most cited articles, major contributors, emerging trends, and noteworthy themes in the field. RESULTS: The results showed that there has been a steady increase in the number of publications on robotic neurosurgery since 1991, with an exponential growth in the number of citations. The United States was the most common country of origin for articles, followed by Canada. The most productive authors in this field were Burton S.A. and Gerszten P.C., while the University of Pittsburgh was the most productive institution, and Neurosurgery was the most productive journal. Themes such as robotics, back pain, and prostate cancer, as well as trends in developing new technologies and improving the precision of surgical procedures, were identified. CONCLUSIONS: This study provides a comprehensive analysis of the most-cited articles on robotic neurosurgery. The broad range of topics and techniques explored emphasize the importance of continued innovation and investigation. Ultimately, the study's findings provide valuable guidance for future research and contribute to advancing our understanding of this critical area of study.

Clinical Trials in Spinal Tumors: A Two-Decade Review.

OBJECTIVE: Clinical trials are essential for assessing the advancements in spine tumor therapeutics. The purpose of the present study was to characterize the trends in clinical trials for primary and metastatic tumor treatment during the past 2 decades. METHODS: The ClinicalTrials.gov database was queried using the search term "spine" for all interventional studies from 1999 to 2020 with the categories of "cancer," "neoplasm," "tumor," and/or "metastasis." The tumor type, phase data, enrollment numbers, and home institution country were recorded. The sponsor was categorized as an academic institution, industry, government, or other and the intervention type as procedure, drug, device, radiation therapy, or other. The frequency of each category and the cumulative frequency during the 20-year period were calculated. RESULTS: A total of 106 registered trials for spine tumors were listed. All, except for 2, that had begun before 2008 had been completed. An enrollment of 51-100 participants (29.8%) was the most common, and most were phase II studies (54.4%). Most of the studies had examined metastatic tumors (58.5%), and the number of new trials annually had increased 3.4-fold from 2009 to 2020. Most of the studies had been conducted in the United States (56.4%). The most common intervention strategy was radiation therapy (32.1%), although from 2010 to 2020, procedural studies had become the most frequent (2.4/year). Most of the studies had been sponsored by academic institutions (63.2%), which during the 20-year period had sponsored 3.2-fold more studies compared with the industry partners. CONCLUSIONS: The number of clinical trials for spine tumor therapies has rapidly increased during the past 15 years, owing to studies at U.S. academic medical institutions investigating radiosurgery for the treatment of metastases. Targeted therapies for tumor subtypes and sequelae have updated international best practices.

The Impact of American Society of Anesthesiologists Status on Cost of Care and Length of Stay Following Posterior Cervical Decompression and Fusion.

BACKGROUND: Increased posterior cervical decompression and fusion (PCDF) procedures over the past decade have raised the prospect of bundled payment plans. The American Society of Anesthesiologists (ASA) Physical Status Classification system may enable accurate estimation of health care costs, length of stay (LOS), and other postoperative outcomes in patients undergoing PCDF. METHODS: Low (I and II) versus high (III and IV) ASA class was used to evaluate 971 patients who underwent PCDF between 2008 and 2016 at a single institution. Demographics were compared using univariate analysis. Cost of care, LOS, and postoperative complications were compared using multivariable logistic and linear regression, controlling for sex, age, length of surgery, and number of segments fused. RESULTS: The high ASA class cohort was older (mean age 62 years vs. 55 years, P < 0.0001) and had higher Elixhauser comorbidity index scores (P < 0.0001). ASA class was independently associated with longer LOS (2.1 days, 95% confidence interval [CI] 1.3-2.9, P < 0.0001) and higher cost ($2936, 95% CI $1457-$4415, P < 0.0001). Patients with high ASA class were more likely to have a nonhome discharge (3.9, 95% CI 2.8-5.6, P < 0.0001), delayed extubation (3.2, 95% CI 1.4-7.3, P = 0.006), intensive care unit stay (2.4, 95% CI 1.5 3.7, P = 0.0001), in-hospital complications (1.5, 95% CI 1.0-2.2, P = 0.03), and 30-day (3.2, 95% CI 1.5-6.8, P = 0.003) and 90-day (3.2, 95% CI 1.8-5.7, P = 0.0001) readmission. CONCLUSIONS: High ASA class is strongly associated with increased costs, LOS, and adverse outcomes following PCDF and could be useful for preoperative prediction of these outcomes.

Comparison of Anterior and Posterior Surgical Approaches for Treatment of Thoracic Myelopathy.

OBJECTIVE: To study a large multi-institutional sample of patients undergoing anterior versus posterior approaches for surgical decompression of thoracic myelopathy. METHODS: The American College of Surgeons National Surgical Quality Improvement Program was queried for patients who underwent decompression for thoracic myelopathy between 2007 and 2015 via anterior or posterior approaches. Patients were excluded if they were undergoing surgery for tumors to isolate a degenerative cohort. Demographics, patient comorbidities, operative details, and postoperative complications were compared between the 2 cohorts. RESULTS: Although there were no differences in age (P = 0.06), sex (P = 0.72), or American Society of Anesthesiologists class (P = 0.59), there were higher rates of steroid use (P = 0.01) and hematologic disorders that predispose to bleeding (P = 0.04) at baseline in the posterior approach cohort. The posterior approach patients had longer operative times (P = 0.03), but there were no differences in length of stay (P = 0.64). Although there were no significant differences in the rates of major organ system complications or return to the operating room (P = 0.52), the posterior approach cohort displayed a trend toward increased severe adverse complications (29.8% vs. 17.6%, P = 0.28) compared with the anterior approach cohort. CONCLUSION: Although the anterior approach to surgical decompression of thoracic myelopathy demonstrated a lower complication rate, this result did not reach statistical significance. The anterior approach was associated with significantly shorter mean operative time, but otherwise there were no significant differences in operative or postoperative outcomes. These findings may support the favorability of the anterior approach but warrant further investigation in a larger study.

Current innovation in virtual and augmented reality in spine surgery.

In spinal surgery, outcomes are directly related both to patient and procedure selection, as well as the accuracy and precision of instrumentation placed. Poorly placed instrumentation can lead to spinal cord, nerve root or vascular injury. Traditionally, spine surgery was performed by open methods and placement of instrumentation under direct visualization. However, minimally invasive surgery (MIS) has seen substantial advances in spine, with an ever-increasing range of indications and procedures. For these reasons, novel methods to visualize anatomy and precisely guide surgery, such as intraoperative navigation, are extremely useful in this field. In this review, we present the recent advances and innovations utilizing simulation methods in spine surgery. The application of these techniques is still relatively new, however quickly being integrated in and outside the operating room. These include virtual reality (VR) (where the entire simulation is virtual), mixed reality (MR) (a combination of virtual and physical components), and augmented reality (AR) (the superimposition of a virtual component onto physical reality). VR and MR have primarily found applications in a teaching and preparatory role, while AR is mainly applied in hands-on surgical settings. The present review attempts to provide an overview of the latest advances and applications of these methods in the neurosurgical spine setting.

Comparison of Surgical Outcomes of Microdiskectomy Procedures by Patient Admission Status.

OBJECTIVE: We sought to compare the cost and in-hospital outcomes following lumbar microdiskectomy procedures by admission type. METHODS: Patients undergoing lumbar microdiskectomy at a single institution from 2008 to 2016 following an elective admission (EL) were compared against those who were admitted from the emergency department (ED) or from elsewhere within or outside the hospital system (TR) for their perioperative outcomes and cost. Multivariable modeling controlled for age, sex, self-reported race, Elixhauser comorbidity score, payer type, number of segments, and procedure length. RESULTS: Of the 1249 patients included in this study, 1116 (89.4%) were admitted electively while 123 (9.8%) were admitted from the ED and 10 (0.8%) were transferred from other hospitals. EL patients had significantly lower comorbidity burdens (P < 0.0001). Univariate and multivariable analyses revealed that transfer admission patients experienced significantly longer hospitalizations (ED: +1.7 days; P < 0.0001; TR: +5.3 days; P < 0.0001) and higher direct costs (ED: $1889; P < 0.0001; TR: $7001; P < 0.0001) compared with EL patients. Despite these risks, ED and TR patients only had increased odds of nonhome discharge compared with EL patients (ED: 3.4; P = 0.002; TR: 7.9; P = 0.02). CONCLUSIONS: Patients admitted as transfers and from the ED had significantly increased hospitalization lengths of stay and direct costs compared with electively admitted patients.

Application of Cooperative Game Theory Principles to Interpret Machine Learning Models of Nonhome Discharge Following Spine Surgery.

STUDY DESIGN: Retrospective analysis of prospectively acquired data. OBJECTIVE: The aim of this study was to identify interaction effects that modulate nonhome discharge (NHD) risk by applying coalitional game theory principles to interpret machine learning models and understand variable interaction effects underlying NHD risk. SUMMARY OF BACKGROUND DATA: NHD may predispose patients to adverse outcomes during their care. Previous studies identified potential factors implicated in NHD; however, it is unclear how interaction effects between these factors contribute to overall NHD risk. METHODS: Of the 11,150 reviewed cases involving procedures for degenerative spine conditions, 1764 cases (15.8%) involved NHD. Gradient boosting classifiers were used to construct predictive models for NHD for each patient. Shapley values, which assign a unique distribution of the total NHD risk to each model variable using an optimal cost-sharing rule, quantified feature importance and examined interaction effects between variables. RESULTS: Models constructed from features identified by Shapley values were highly predictive of patient-level NHD risk (mean C-statistic = 0.91). Supervised clustering identified distinct patient subgroups with variable NHD risk and their shared characteristics. Focused interaction analysis of surgical invasiveness, age, and comorbidity burden suggested age as a worse risk factor than comorbidity burden due to stronger positive interaction effects. Additionally, negative interaction effects were found between age and low blood loss, indicating that intraoperative hemostasis may be critical for reducing NHD risk in the elderly. CONCLUSION: This strategy provides novel insights into feature interactions that contribute to NHD risk after spine surgery. Patients with positively interacting risk factors may require special attention during their hospitalization to control NHD risk.Level of Evidence: 3.

Surgeon experience influences patient characteristics and outcomes in spine deformity surgery.

PURPOSE: To characterize differences in patient demographics and outcomes by surgeon experience in a cohort of patients undergoing adult spinal deformity surgery. METHODS: Patients undergoing degenerative spinal deformity were included. Patients whose surgeons graduated from fellowship ≤ 5 years prior to surgery versus > 5 years were compared. Multivariable linear and logistic regression, controlling for age, sex, comorbidity burden, number of segments fused, blood loss and operative time were used to evaluate differences in outcomes. Characteristics of operative invasiveness were plotted against surgeons' level of experience, and trends in these measures were assessed with univariate linear regression. RESULTS: Three-hundred sixty-three patients were included. 147 patients' surgeons had ≤ 5 years of experience. Patient demographics were evenly matched. Patients with junior surgeons had more pre-existing medical complications, and senior surgeons were less likely to take care of patients with Medicare/Medicaid (p < 0.001). Junior surgeons were more likely to operate on non-elective patients (p < 0.001). Patients of junior surgeons received larger fusions (9.6 vs. 7.6 segments fused, p < 0.001). There were no differences in complication rates or death. Patients of junior surgeons had longer overall length of stays (p = 0.037) and higher rates of nonhome discharge (OR 2.0, p < 0.001), 30- and 90-day (p < 0.005) ED visits, and higher costs (+ $8548, 95% CI: $1596 to $15,502; p = 0.016). CONCLUSION: Junior surgeons tend to perform more extensive deformity operations on more medically complex patients compared to senior surgeons, associated with higher costs and more resource utilization than senior surgeons.

Utility of the Hospital Frailty Risk Score for Predicting Adverse Outcomes in Degenerative Spine Surgery Cohorts.

BACKGROUND: As spine surgery becomes increasingly common in the elderly, frailty has been used to risk stratify these patients. The Hospital Frailty Risk Score (HFRS) is a novel method of assessing frailty using International Classification of Diseases, Tenth Revision (ICD-10) codes. However, HFRS utility has not been evaluated in spinal surgery. OBJECTIVE: To assess the accuracy of HFRS in predicting adverse outcomes of surgical spine patients. METHODS: Patients undergoing elective spine surgery at a single institution from 2008 to 2016 were reviewed, and those undergoing surgery for tumors, traumas, and infections were excluded. The HFRS was calculated for each patient, and rates of adverse events were calculated for low, medium, and high frailty cohorts. Predictive ability of the HFRS in a model containing other relevant variables for various outcomes was also calculated. RESULTS: Intensive care unit (ICU) stays were more prevalent in high HFRS patients (66%) than medium (31%) or low (7%) HFRS patients. Similar results were found for nonhome discharges and 30-d readmission rates. Logistic regressions showed HFRS improved the accuracy of predicting ICU stays (area under the curve [AUC] = 0.87), nonhome discharges (AUC = 0.84), and total complications (AUC = 0.84). HFRS was less effective at improving predictions of 30-d readmission rates (AUC = 0.65) and emergency department visits (AUC = 0.60). CONCLUSION: HFRS is a better predictor of length of stay (LOS), ICU stays, and nonhome discharges than readmission and may improve on modified frailty index in predicting LOS. Since ICU stays and nonhome discharges are the main drivers of cost variability in spine surgery, HFRS may be a valuable tool for cost prediction in this specialty.

The case for T2 pedicle subtraction osteotomy in the surgical treatment of rigid cervicothoracic deformity.

OBJECTIVE: Rigid cervicothoracic kyphotic deformity (CTKD) remains a difficult pathology to treat, especially in the setting of prior cervical instrumentation and fusion. CTKD may result in chronic neck pain, difficulty maintaining horizontal gaze, and myelopathy. Prior studies have advocated for the use of C7 or T1 pedicle subtraction osteotomies (PSOs). However, these surgeries are fraught with danger and, most significantly, place the C7, C8, and/or T1 nerve roots at risk. METHODS: The authors retrospectively reviewed their experience with performing T2 PSO for the correction of rigid CTKD. Demographics collected included age, sex, details of prior cervical surgery, and coexisting conditions. Perioperative variables included levels decompressed, levels instrumented, estimated blood loss, length of surgery, length of stay, complications from surgery, and length of follow-up. Radiographic measurements included C2-7 sagittal vertical axis (SVA) correction, and changes in the cervicothoracic Cobb angle, lumbar lordosis, and C2-S1 SVA. RESULTS: Four male patients were identified (age range 55-72 years). Three patients had undergone prior posterior cervical laminectomy and instrumented fusion and developed postsurgical kyphosis. All patients underwent T2 PSO: 2 patients received instrumentation at C2-T4, and 2 patients received instrumentation at C2-T5. The median C2-7 SVA correction was 3.85 cm (range 2.9-5.3 cm). The sagittal Cobb angle correction ranged from 27.8° to 37.6°. Notably, there were no neurological complications. CONCLUSIONS: T2 PSO is a powerful correction technique for the treatment of rigid CTKD. Compared with C7 or T1 PSO, there is decreased risk of injury to intrinsic hand muscle innervators, and there is virtually no risk of vertebral artery injury. Laminectomy may also be safer, as there is less (or no) scar tissue from prior surgeries. Correction at this distal level may allow for a greater sagittal correction. The authors are optimistic that these findings will be corroborated in larger cohorts examining this challenging clinical entity.

Factors Affecting Length of Stay Following Elective Anterior and Posterior Cervical Spine Surgery.

Background Disease of the cervical spine is widely prevalent, most commonly secondary to degenerative disc changes and spondylosis. Objective The goal of the paper was to identify a possible discrepancy regarding the length of stay (LOS) between the anterior and posterior approaches to elective cervical spine surgery and identify contributing factors. Methods A retrospective study was performed on 587 patients (341 anterior, 246 posterior) that underwent elective cervical spinal surgery between October 2001 and March 2014. Pre- and intraoperative data were analyzed. Statistical analysis was performed using GraphPad Prism 5 (GraphPad Software, Inc., La Jolla, CA) and the Statistical Package for Social Sciences (SPSS) (IBM SPSS Statistics, Armonk, NY). Results Average LOS was 3.21 ± 0.32 days for patients that benefited from the anterior approach cervical spinal surgery and 5.28 ± 0.37 days for patients that benefited from the posterior approach surgery, P-value < 0.0001. Anterior patients had lower American Society of Anesthesiologists scores (2.43 ± 0.036 vs. 2.70 ± 0.044). Anterior patients also had fewer intervertebral levels operated upon (2.18 ± 0.056 vs. 4.11 ± 0.13), shorter incisions (5.49 ± 0.093 cm vs. 9.25 ± 0.16 cm), lower estimated blood loss (EBL) (183.8 ± 9.0 cc vs. 340.0 ± 8.7 cc), and shorter procedure times (4.12 ± 0.09 hours vs. 4.47 ± 0.10 hours). Chi-squared tests for hypertension, coronary artery disease, congestive heart failure, chronic obstructive pulmonary disease, and asthma showed no significant difference between groups. CONCLUSIONS: Patients with anterior surgery performed experienced a length of stay that was 2.07 days shorter on average. Higher EBL, longer incisions, more intervertebral levels, and longer operating time were significantly associated with the posterior approach. Future studies should include multiple surgeons. The goal would be to create a model that could accurately predict the postoperative length of stay based on patient and operative factors.

Reduced Surgical Site Infection Rates Following Spine Surgery Using an Enhanced Prophylaxis Protocol.

BACKGROUND: Postoperative surgical site infection (SSI) is a common complication after spine surgery. Reduction of SSI has many benefits including, but not limited to, the reduced length of stay, readmission rates, and morbidity and mortality. OBJECTIVE: To determine whether an enhanced antibiotic prophylaxis reduced the rate of surgical site infections in spine surgery. METHODS: This is a retrospective observation study which analyzed the incidence of postoperative SSI following a consecutive series of 1,486 cervical, thoracic and lumbar spine operations performed at a single institution by the senior author between the dates of October 2001 to March 2014. Patients with surgeries between October 2001 and November 2005 received a standard institutional antibiotic prophylaxis. Patients between December 2005 and March 2014 underwent an enhanced antibiotic protocol. RESULTS: A total of nine cases met the criteria for SSI. All nine cases were recorded during the initial time period when the standard institutional prophylaxis was used. Further, these cases were only observed under posterior operative approaches. No further cases of SSI were observed after the institution of the enhanced antibiotic prophylaxis (p < 0.0001). This was statistically significant in the cervical and lumbar regions (p < 0.0042 and p < 0.0119, respectively). CONCLUSIONS: Although difficult to predict the incidence of SSI, this study found that the use of an enhanced antibiotic prophylaxis protocol significantly reduced one surgeon's overall rates of surgical site infections after spine surgery.

Review of Assessment Scales for Diagnosing and Monitoring Sports-related Concussion.

Sports-related concussion has emerged as a public health crisis due to increased diagnosis of the condition and increased participation in organized and recreational athletics worldwide. Under-recognition of concussions can lead to premature clearance for athletic participation, leaving athletes vulnerable to repeat injury and subsequent short- and long-term complications. There is overwhelming evidence that assessment and management of sports-related concussions should involve a multifaceted approach. A number of assessment criteria have been developed for this purpose. It is important to understand the available and emerging diagnostic testing modalities for sports-related concussions. The most commonly used tools for evaluating individuals with concussion are the Post-Concussion Symptom Scale (PCSS), Standard Assessment of Concussion (SAC), Standard Concussion Assessment Tool (SCAT3), and the most recognized computerized neurocognitive test, the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT). The strengths and limitations of each of these tools, and the Concussion Resolution Index (CRI), CogSport, and King-Devick tests were evaluated. Based on the data, it appears that the most sensitive and specific of these is the ImPACT test. Additionally, the King-Devick test is an effective adjunct due to its ability to test eye movements and brainstem function.

Major Histocompatibility Complex class I proteins are critical for maintaining neuronal structural complexity in the aging brain.

Major histocompatibility complex class I (MHCI) proteins have been implicated in neuronal function through the modulation of neuritogenesis, synaptogenesis, synaptic plasticity, and memory consolidation during development. However, the involvement of MHCI in the aged brain is unclear. Here we demonstrate that MHCI deficiency results in significant dendritic atrophy along with an increase in thin dendritic spines and a reduction in stubby spines in the hippocampus of aged (12 month old) mice. Ultrastructural analyses revealed a decrease in spine head diameter and post synaptic density (PSD) area, as well as an increase in overall synapse density, and non-perforated, small spines. Interestingly, we found that the changes in synapse density and morphology appear relatively late (after the age of 6 months). Finally, we found a significant age dependent increase in the levels of the glutamate receptor, GluN2B in aged MHCI knockout mice, with no change in GluA2/3, VGluT1, PSD95 or synaptophysin. These results indicate that MHCI may be also be involved in maintaining brain integrity at post-developmental stages notably in the modulation of neuronal and spine morphology and synaptic function during non-pathological aging which could have significant implications for cognitive function.

Differential induction of plasma cells by isoforms of human TACI.

Subjects with common variable immune deficiency may have mutations in transmembrane activator calcium modulator and cyclophilin ligand interactor (TACI). Unlike the murine gene, human TACI undergoes alternative messenger (m)RNA splicing to produce isoforms with 1 or 2 ligand-binding domains. Because both isoforms are found in human B cells, we compared their functions in transduced murine B and human pre-B cells. Although murine cells and pre-B cells transduced with the long TACI isoform retained surface CD19 and immunoglobulin G, cells transduced with the short TACI isoform completely lost these B-cell characteristics. Expression of the short TACI isoform produced intense nuclear factor κB activation, nuclear p65 translocation, and colocalization with myeloid differentiation factor 88 and calcium-modulating cyclophilin ligand. The short TACI-transduced cells became larger and CD138 positive, demonstrated upregulated BLIMP1 and XBP1 mRNA, and acquired the morphology of plasma cells. In contrast, cells bearing the long isoform had significantly less BLIMP1 and XBP1 mRNA and, for human pre-B cells, remained CD138 negative. Although human B cells express both isoforms, the short isoform predominates in CD27(+) B cells, toll-like receptor 9-activated peripheral B cells, and splenic marginal zone B cells. Although the transcriptional controls for alternative splicing of isoforms remain unknown, differential signals via isoforms may control plasma-cell generation in humans.

Selective vulnerability of the cerebral vasculature to blast injury in a rat model of mild traumatic brain injury.

BACKGROUND: Blast-related traumatic brain injury (TBI) is a common cause of injury in the military operations in Iraq and Afghanistan. How the primary blast wave affects the brain is not well understood. The aim of the present study was to examine whether blast exposure affects the cerebral vasculature in a rodent model. We analyzed the brains of rats exposed to single or multiple (three) 74.5 kPa blast exposures, conditions that mimic a mild TBI. Rats were sacrificed 24 hours or between 6 and 10 months after exposure. Blast-induced cerebral vascular pathology was examined by a combination of light microscopy, immunohistochemistry, and electron microscopy. RESULTS: We describe a selective vascular pathology that is present acutely at 24 hours after injury. The vascular pathology is found at the margins of focal shear-related injuries that, as we previously showed, typically follow the patterns of penetrating cortical vessels. However, changes in the microvasculature extend beyond the margins of such lesions. Electron microscopy revealed that microvascular pathology is found in regions of the brain with an otherwise normal neuropil. This initial injury leads to chronic changes in the microvasculature that are still evident many months after the initial blast exposure. CONCLUSIONS: These studies suggest that vascular pathology may be a central mechanism in the induction of chronic blast-related injury.

Blast overpressure induces shear-related injuries in the brain of rats exposed to a mild traumatic brain injury.

BACKGROUND: Blast-related traumatic brain injury (TBI) has been a significant cause of injury in the military operations of Iraq and Afghanistan, affecting as many as 10-20% of returning veterans. However, how blast waves affect the brain is poorly understood. To understand their effects, we analyzed the brains of rats exposed to single or multiple (three) 74.5 kPa blast exposures, conditions that mimic a mild TBI. RESULTS: Rats were sacrificed 24 hours or between 4 and 10 months after exposure. Intraventricular hemorrhages were commonly observed after 24 hrs. A screen for neuropathology did not reveal any generalized histopathology. However, focal lesions resembling rips or tears in the tissue were found in many brains. These lesions disrupted cortical organization resulting in some cases in unusual tissue realignments. The lesions frequently appeared to follow the lines of penetrating cortical vessels and microhemorrhages were found within some but not most acute lesions. CONCLUSIONS: These lesions likely represent a type of shear injury that is unique to blast trauma. The observation that lesions often appeared to follow penetrating cortical vessels suggests a vascular mechanism of injury and that blood vessels may represent the fault lines along which the most damaging effect of the blast pressure is transmitted.

Evidence for reduced experience-dependent dendritic spine plasticity in the aging prefrontal cortex.

Cognitive functions that require the prefrontal cortex are highly sensitive to aging in humans, nonhuman primates, and rodents, although the neurobiological correlates of this vulnerability remain largely unknown. It has been proposed that dendritic spines represent the primary site of structural plasticity in the adult brain, and recent data have supported the hypothesis that aging is associated with alterations of dendritic spine morphology and plasticity in prefrontal cortex. However, no study to date has directly examined whether aging alters the capacity for experience-dependent spine plasticity in aging prefrontal neurons. To address this possibility, we used young, middle-aged, and aged rats in a behavioral stress paradigm known to produce spine remodeling in prefrontal cortical neurons. In young rats, stress resulted in dendritic spine loss and altered patterns of spine morphology; in contrast, spines from middle-aged and aged animals were remarkably stable and did not show evidence of remodeling. The loss of stress-induced spine plasticity observed in aging rats occurred alongside robust age-related reductions in spine density and shifts in remaining spine morphology. Together, the data presented here provide the first evidence that experience-dependent spine plasticity is altered by aging in prefrontal cortex, and support a model in which dendritic spines become progressively less plastic in the aging brain.