Neurosurgery Commons^™

Integrated Transcriptomic Landscape Of Medulloblastoma And Ependymoma Reveals Novel Tumor Subtype-Specific Biology, Sonali Arora, Nicholas Nuechterlein, Matt Jensen, Gregory Glatzer, Philipp Sievers, Srinidhi Varadharajan, Andrey Korshunov, Felix Sahm, Stephen C Mack, Michael D Taylor, Taranjit S Gujral, Eric C Holland

Faculty, Staff and Students Publications

Background: Medulloblastoma and ependymoma are common pediatric central nervous system tumors with significant molecular and clinical heterogeneity. While molecular subgrouping has enabled classification into molecular subtypes, the extent of heterogeneity within these subgroups remains poorly defined.

Methods: We collected bulk RNA sequencing data from 888 medulloblastoma and 370 ependymoma tumors to establish a comprehensive reference landscape. After rigorous batch effect correction, normalization, and dimensionality reduction, we generated a unified landscape to explore gene expression, signaling pathways, RNA fusions, and copy number variations.

Results: Our transcriptional analysis revealed distinct clustering patterns, including two primary ependymoma compartments, EPN-E1 and EPN-E2, each with …

Unveiling Spatial Heterogeneity In Medulloblastoma: A Multi-Omics Analysis Of Cellular State And Geographical Organization, Jiankang Li, Hailong Liu, Ziwei Wang, Jiao Zhang, Xuan Chen, Craig Daniels, Xiaochong Wu, Olivier Saulnier, Hiromichi Suzuki, Pasqualino De Antonellis, Alexandra Rasnitsyn, Winnie Ong, Evan Y Wang, Liam D Hendrikse, Yu Su, Yu Tian, Dongming Han, Ruohan Wang, Jialin Mo, Fei Liu, Kaiwen Deng, Dongyang Wang, Zhaoyang Feng, Yifei Jiang, Yanong Li, Yuting Ma, Zijia Liu, Meiyu Li, Peiyi Tian, Yanfeng Shi, Yong Jiang, Tao Yang, Shouwei Li, Jianfeng Liang, Jingchuan Wu, Ying Wang, Wanjing Zou, Yina Jiang, Lusheng Wang, Fang Chen, Xin Jin, Shuaicheng Li, Xiaoguang Qiu, Chunde Li, Ya Gao, Yujie Tang, Michael D Taylor, Tao Jiang

Faculty, Staff and Students Publications

Background: Despite numerous studies on medulloblastoma (MB) cell heterogeneity, the spatial characteristics of cellular states remain unclear.

Methods: We analyze single-nucleus and spatial transcriptomes and chromatin accessibility from human MB spanning four subgroups, to identify malignant cell populations and describe the spatial evolutionary trajectories. The spatial copy number variations (CNVs) patterns and niches were analyzed to investigate the cellular interactions.

Results: Three main malignant cell populations were identified, including progenitor-like, cycling, and differentiated populations. Gene signatures of cell populations strongly correlate to clinical outcomes. These tumor cell populations are geographically organized as stem-like and mature regions, highlighting their spatially heterogeneous …

Assessment Of Cerebrospinal Fluid And Blood-Based Biomarkers In Degenerative Cervical Myelopathy: Systematic Review And Meta-Analysis, Harshit Arora, Hassan Darabi, Cassandra C. Wolsh, Kelsey N. Karnik, John C. Gensel, Francis Farhadi

Neurosurgery Faculty Publications

Study Design: Systematic Review and Meta-Analysis.

Objectives: Degenerative cervical myelopathy (DCM), the leading cause of spinal cord injury globally, may clinically manifest with hand numbness and tingling, loss of hand dexterity and impaired balance and gait. Biomarkers have been identified as disease indicators with recent studies exploring the role of structural and inflammatory biomarkers in diagnostic and treatment outcome prediction. The review aims to identify relevant cerebrospinal fluid (CSF) and blood-based biomarkers associated with DCM diagnosis and prognostication.

Methods: The systematic review was conducted as per PRISMA guidelines. A comprehensive search strategy was devised to identify articles evaluating biomarkers in …

Implications And Pathophysiology Of Neuroinflammation In Pediatric Patients With Traumatic Brain Injury: An Updated Review, Shalin S Shah, Arya J Shetty, David T Johnston, Caroline L Hanan, Brendan T O'Reilly, Max A Skibber, Ahmed T Massoud, Banghe Zhu, Eva M Sevick-Muraca, Jenifer Juranek, Charles S Cox, Manish N Shah

Faculty, Staff and Student Publications

Traumatic Brain Injury (TBI) in children is a profound public health issue with the potential to disrupt cognitive, behavioral, and psychosocial development significantly. This review provides an updated examination of the role of neuroinflammation in pediatric TBI, emphasizing its dual impact on injury progression and recovery. Highlighted is the complex interplay of primary and secondary injury mechanisms, including the critical contributions of neuroinflammatory responses mediated by central and peripheral immune cells. Advances in biomarker identification and imaging techniques are discussed, showcasing how tools like diffusion tensor imaging (DTI) and positron emission tomography (PET) enhance our understanding of neuroinflammatory processes. The …

The Geriatric Nutritional Risk Index As A Predictor Of Complications In Geriatric Trauma Patients, Daniel H Wang, Yoko Fujita, Antonio Dono, Ana G Rodriguez Armendariz, Mauli Shah, Nagireddy Putluri, Pavel S Pichardo-Rojas, Chirag B Patel, Jay-Jiguang Zhu, Jason T Huse, Brittany C Parker Kerrigan, Frederick F Lang, Yoshua Esquenazi, Leomar Y Ballester

Faculty, Staff and Student Publications

Cerebrospinal fluid (CSF) analysis is underutilized in patients with glioblastoma (GBM), partly due to a lack of studies demonstrating the clinical utility of CSF biomarkers. While some studies show the utility of CSF cell-free DNA analysis, studies analyzing CSF metabolites in patients with glioblastoma are limited. Diffuse gliomas have altered cellular metabolism. For example, mutations in isocitrate dehydrogenase enzymes (e.g., IDH1 and IDH2) are common in diffuse gliomas and lead to increased levels of D-2-hydroxyglutarate in CSF. However, there is a poor understanding of changes CSF metabolites in GBM patients. In this study, we performed targeted metabolomic analysis of CSF …

Plasma Biomarkers For Brain Injury In Extracorporeal Membrane Oxygenation, Shrey Kapoor, Anna Kolchinski, Aaron M Gusdon, Lavienraj Premraj, Sung-Min Cho

Faculty, Staff and Student Publications

Extracorporeal membrane oxygenation (ECMO) is a life-saving intervention for patients with refractory cardiorespiratory failure. Despite its benefits, ECMO carries a significant risk of neurological complications, including acute brain injury (ABI). Although standardized neuromonitoring and neurological care have been shown to improve early detection of ABI, the inability to perform neuroimaging in a timely manner is a major limitation in the accurate diagnosis of neurological complications. Therefore, blood-based biomarkers capable of detecting ongoing brain injury at the bedside are of great clinical significance. This review aims to provide a concise review of the current literature on plasma biomarkers for ABI in …

Leucine-Rich Alpha-2-Glycoprotein 1 Is A Systemic Biomarker Of Early Brain Injury And Delayed Cerebral Ischemia After Subarachnoid Hemorrhage, Jude P J Savarraj, Devin W Mcbride, Eunsu Park, Sarah Hinds, Atzhiry Paz, Aaron Gusdon, Ren Xuefang, Sheng Pan, Hilda Ahnstedt, Gabriela Delevati Colpo, Eunhee Kim, Zhongming Zhao, Louise Mccullough, Huimahn Alex Choi

Faculty, Staff and Student Publications

BACKGROUND: After subarachnoid hemorrhage (SAH), early brain injury (EBI) and delayed cerebral ischemia (DCI) lead to poor outcomes. Discovery of biomarkers indicative of disease severity and predictive of DCI is important. We tested whether leucine-rich alpha-2-glycoprotein 1 (LRG1) is a marker of severity, DCI, and functional outcomes after SAH.

METHODS: We performed untargeted proteomics using mass spectrometry in plasma samples collected at < 48 h of SAH in two independent discovery cohorts (n = 27 and n = 45) and identified LRG1 as a biomarker for DCI. To validate our findings, we used enzyme-linked immunosorbent assay and confirmed this finding in an internal validation cohort of plasma from 72 study participants with SAH (22 DCI and 50 non-DCI). Further, we investigated the relationship between LRG1 and markers of EBI, DCI, and poor functional outcomes (quantified by the modified Rankin Scale). We also measured cerebrospinal fluid (CSF) levels of LRG1 and investigated its relationship to EBI, DCI, and clinical outcomes.

RESULTS: Untargeted proteomics revealed higher plasma LRG1 levels across EBI severity and DCI in both discovery cohorts. In the validation cohort, the levels of LRG1 were higher in the DCI group compared with the non-DCI group (mean (SD): …

Tale Of Two Cities: Narrative Review Of Oxygen, Sung-Ho Ahn, Angela Burkett, Atzhiry Paz, Jude P Savarraj, Sarah Hinds, Georgene Hergenroeder, Aaron M Gusdon, Xuefeng Ren, Jeong-Ho Hong, Huimahn A Choi

Faculty, Staff and Student Publications

BACKGROUND: Cerebral edema (CE) at admission is a surrogate marker of 'early brain injury' (EBI) after subarachnoid hemorrhage (SAH). Only recently has the focus on the changes in CE after SAH such as delayed resolution or newly developed CE been examined. Among several factors, an early systemic inflammatory response has been shown to be associated with CE. We investigate inflammatory markers in subjects with early CE which does not resolve, i.e., persistent CE after SAH.

METHODS: Computed tomography scans of SAH patients were graded at admission and at 7 days after SAH for CE using the 0-4 'subarachnoid hemorrhage early …

Intracranial Vcam1 At Time Of Mechanical Thrombectomy Predicts Ischemic Stroke Severity, Benton Maglinger, Madison Sands, Jacqueline A. Frank, Christopher J. Mclouth, Amanda L. Trout, Jill M. Roberts, Stephen Grupke, Jadwiga Turchan-Cholewo, Ann M. Stowe, Justin F. Fraser, Keith R. Pennypacker

Behavioral Science Faculty Publications

BACKGROUND: Emergent large vessel occlusion (ELVO) strokes are devastating ischemic vascular events for which novel treatment options are needed. Using vascular cell adhesion molecule 1 (VCAM1) as a prototype, the objective of this study was to identify proteomic biomarkers and network signaling functions that are potential therapeutic targets for adjuvant treatment for mechanical thrombectomy.

METHODS: The blood and clot thrombectomy and collaboration (BACTRAC) study is a continually enrolling tissue bank and registry from stroke patients undergoing mechanical thrombectomy. Plasma proteins from intracranial (distal to clot) and systemic arterial blood (carotid) were analyzed by Olink Proteomics for N=42 subjects. Statistical …

Translational Evaluation Of Acid/Base And Electrolyte Alterations In Rodent Model Of Focal Ischemia, Sarah R. Martha, Lisa A. Collier, Stephanie M. Davis, Hilary A. Seifert, Christopher C. Leonardo, Craig T. Ajmo, Elspeth A. Foran, Justin F. Fraser, Keith R. Pennypacker

Neurology Faculty Publications

BACKGROUND AND PURPOSE: Acid/base and electrolytes could provide clinically valuable information about cerebral infarct core and penumbra. We evaluated associations between acid/base and electrolyte changes and outcomes in 2 rat models of stroke, permanent, and transient middle cerebral artery occlusion.

METHODS: Three-month old Sprague-Dawley rats underwent permanent or transient middle cerebral artery occlusion. Pre- and post-middle cerebral artery occlusion venous samples for permanent and transient models provided pH, carbon dioxide, oxygen, glucose, and electrolyte values of ionized calcium, potassium, and sodium. Multiple regression determined predictors of infarct volume from these values, and Kaplan-Meier curve analyzed morality between permanent and transient …

Improving Schizophrenia Diagnosis Through Biomarkers: An Upcoming Prospect, Syed Mohammad Asad Zaidi, Abdul Latif Bikak, Rameez-Ul Hassan

Medical College Documents

No abstract provided.