Neurosciences Commons^™

A Potential Vegf-Driven Hypothesis Of Calvarial Centripetal Proliferation In Cerebral Proliferative Angiopathy, Shigeta Miyake, Timo Krings, Tze Phei Kee, Thierry A G M Huisman

Faculty, Staff and Students Publications

Cerebral proliferative angiopathy (CPA) is a rare subtype of cerebral arteriovenous malformation, characterized by unique angiographic features and clinical presentations. Although the clinical and angiographic characteristics of CPA have been well described, their impact on the surrounding tissues remains underexplored. Herein, we investigated the presence of calvarial thickening in patients with CPA, and discuss its potential pathogenesis. This retrospective multicenter cohort study enrolled 16 CPA patients from our institutions. Patients were identified by a search of the hospital medical records for key words related to "cerebral proliferative angiopathy." Data on demographics, CPA characteristics, clinical symptoms, and calvarial thickening were collected …

Does Body Mass Index Influence Intraoperative Costs And Operative Times For Open Transforaminal Lumbar Interbody Fusion? A Time-Driven Activity-Based Costing Analysis, Danyal A. Quraishi, Advith Sarikonda, Dwight M. Self, Emily Isch, Steven R. Glener, Arbaz A. Momin, Ashmal Sami, Nicholas Clark, Joshua Pelta-Heller, Srinivas Prasad, Ashwini Sharan, Jack Jallo, James Harrop, Alex R. Vaccaro, Ahilan Sivaganesan

Department of Neuroscience Faculty Papers

BACKGROUND: The increasing prevalence of obesity has raised concerns about its impact on surgical outcomes and healthcare costs. This study evaluates the influence of Body Mass Index (BMI) on intraoperative costs and operative times during open Transforaminal Lumbar Interbody Fusion (TLIF) procedures using a Time-Driven Activity-Based Costing (TDABC) approach.

METHODS: A retrospective analysis was conducted on 279 patients who underwent TLIF between 2019 and 2022. Patients were categorized into 5 BMI cohorts: healthy weight (BMI 18.5-24.99), overweight (BMI 25.0-29.99), Class I obese (BMI 30.0-34.99), Class II obese (BMI 35.0-39.99), and Class III obese (BMI >40). Intraoperative costs were calculated using …

Supplementary Motor Area In Speech Initiation: A Large-Scale Intracranial Eeg Evaluation Of Stereotyped Word Articulation, Latané Bullock, Kiefer J Forseth, Oscar Woolnough, Patrick S Rollo, Nitin Tandon

Faculty, Staff and Student Publications

Speech production engages a distributed network of cortical and subcortical brain regions. The supplementary motor area (SMA) has long been thought to be a key hub in coordinating across these regions to initiate voluntary movements, including speech. We analyzed direct intracranial recordings from 115 patients with epilepsy as they articulated a single word in a subset of trials from a picture-naming task. We aimed to characterize the temporal dynamics of SMA relative to other cortical regions. SMA and preSMA were among the first regions to activate after cue onset, peaked in activity before articulation onset, and were the earliest regions …

Investigating The Role Of Endothelin-1 In Reactive Astrocytosis, Candace Betancourt-Szymanowska

Master's Theses

Glaucoma is a progressive optic neuropathy which results in blindness for many patients, even with treatment. Endothelin-1 (ET-1) is a vasoactive peptide known to be aberrantly upregulated in the eyes of individuals with glaucoma. Optic nerve head astrocytes (ONHA) are the resident glial cell of the optic nerve head and are among the first cell types to undergo changes to a reactive phenotype. In this thesis, we investigated the role of ET-1 overexpression and its putative role in eliciting a reactive phenotype in ONHA by inducing lentiviral-mediated over-expression of EDN1. ONHA transduced with EDN1 (ONHA ET-1) were verified to be …

Sex Differences In Response To Diet Enriched With Glutathione Precursors In The Aging Heart, Aude Angelini, Grecia Garcia Marquez, Anna Malovannaya, Marta L Fiorotto, Alexander Saltzman, Antrix Jain, Joann Trial, George E Taffet, Katarzyna A Cieslik

Faculty, Staff and Students Publications

Common features of the aging heart are dysregulated metabolism, inflammation, and fibrosis. Elevated oxidative stress is another hallmark of cardiac aging that can exacerbate each of these conditions. We hypothesize that by increasing natural antioxidant levels (glutathione), we will improve cardiac function. Twenty-one-month-old mice were fed glycine and N-acetyl cysteine (GlyNAC; glutathione precursors)-supplemented or control diets for 12 weeks. Heart function was monitored longitudinally, and the exercise performance was determined at the end of the study. We found that the GlyNAC diet was beneficial for old male but not old female mice, leading to an increase of Ndufb8 expression (a …

Dose–Response Of Tdcs Effects On Motor Learning And Cortical Excitability: A Preregistered Study, Gavin Hsu, Zhenous Hadi Jafari, Abdelrahman Ahmed, Dylan J. Edwards, Leonardo G. Cohen, Lucas C. Parra

Research outputs 2022 to 2026

Multiple studies have demonstrated that transcranial direct current stimulation (tDCS) of the primary motor cortex (M1) can influence corticospinal excitability and motor skill acquisition. However, the evidence for these effects is inconsistent, and a common neural substrate for these effects has not been directly demonstrated. To address this, we hypothesized that higher tDCS intensities would produce more robust effects, and uncover their relationship. In this preregistered study, 120 participants engaged in a motor skill learning task while receiving tDCS with posterior-to-anterior currents through M1. We employed a double-blind, between-subjects design, with groups of 4 mA, 6 mA, or sham stimulation, …

Foxr2 Targets Lhx6+/Dlx+ Neural Lineages To Drive Central Nervous System Neuroblastoma, Selin Jessa, Antonella De Cola, Bhavyaa Chandarana, Michael Mcnicholas, Steven Hébert, Adam Ptack, Damien Faury, Jessica W Tsai, Andrey Korshunov, Timothy N Phoenix, Benjamin Ellezam, David T W Jones, Michael D Taylor, Pratiti Bandopadhayay, Manav Pathania, Nada Jabado, Claudia L Kleinman

Faculty, Staff and Students Publications

Central nervous system neuroblastoma with forkhead box R2 (FOXR2) activation (NB-FOXR2) is a high-grade tumor of the brain hemispheres and a newly identified molecular entity. Tumors express dual neuronal and glial markers, leading to frequent misdiagnoses, and limited information exists on the role of FOXR2 in their genesis. To identify their cellular origins, we profiled the transcriptomes of NB-FOXR2 tumors at the bulk and single-cell levels and integrated these profiles with large single-cell references of the normal brain. NB-FOXR2 tumors mapped to LHX6+/DLX+ lineages derived from the medial ganglionic eminence, a progenitor domain in the ventral telencephalon. In vivo prenatal …

Is Modulation Of Immune Checkpoints On Glioblastoma-Infiltrating Myeloid Cells A Viable Therapeutic Strategy?, Ruochen Du, Jianzhong Zhang, Rimas V Lukas, Shashwat Tripathi, Jared T Ahrendsen, Michael A Curran, Crismita Dmello, Peng Zhang, Roger Stupp, Ganesh Rao, Amy B Heimberger

Faculty, Staff and Students Publications

The field of immunology has traditionally focused on immune checkpoint modulation of adaptive immune cells. However, many malignancies such as glioblastoma are mostly devoid of T cells and rather are enriched with immunosuppressive myeloid cells of the innate immune system. While some immune checkpoint targets are shared between adaptive and innate immunity, myeloid-specific checkpoints could also serve as potential therapeutics. To better understand the impact of immune checkpoint blockade on myeloid cells, we systematically summarize the current literature focusing on the direct immunological effects of PD-L1/PD-1, CD24/Siglec-10, collagen/LAIR-1, CX3CL1/CX3CR1, and CXCL10/CXCR3. By synthesizing the molecular mechanisms and the translational implications, …

Alzheimer’S Disease: Relationship Of Cognition And Behavior To Neurochemistry, Peter J. Whitehouse

Faculty Scholarship

Alzheimer’s disease is characterized by loss of cells and synapses in specific neural systems. The development of more effective therapies will depend on understanding the relationships between this pathology and the cognitive and behavioral impairments. In this review, focusing primarily on work in our laboratory, we will examine both classic and neuropeptide neurotransmitter systems and will discuss conceptual and methodological problems in relating clinical and biological measures.

Molecular Logic For Cellular Specializations That Initiate The Auditory Parallel Processing Pathways, Junzhan Jing, Ming Hu, Tenzin Ngodup, Qianqian Ma, Shu-Ning Natalie Lau, M Cecilia Ljungberg, Matthew J Mcginley, Laurence O Trussell, Xiaolong Jiang

Faculty, Staff and Students Publications

The cochlear nuclear complex (CN), the starting point for all central auditory processing, encompasses a suite of neuronal cell types highly specialized for neural coding of acoustic signals. However, the molecular logic governing these specializations remains unknown. By combining single-nucleus RNA sequencing and Patch-seq analysis, we reveal a set of transcriptionally distinct cell populations encompassing all previously observed types and discover multiple hitherto unknown subtypes with anatomical and physiological identity. The resulting comprehensive cell-type taxonomy reconciles anatomical position, morphological, physiological, and molecular criteria, enabling the determination of the molecular basis of the specialized cellular phenotypes in the CN. In particular, …

Building Toward Population Reserve And A Critical Positive Psychiatry, Peter J. Whitehouse

Faculty Scholarship

No abstract provided.

Two-Year Follow-Up Of Gait And Postural Control Following Initiation Of Recombinant Human Tripeptidyl Intracerebroventricular Enzyme Replacement Therapy In Two Atypical Cln2 Patients, Rahul Soangra, Marybeth Grant-Beuttler, Harriet Chang, Raymond Y. Wang

Physical Therapy Faculty Articles and Research

Neuronal ceroid lipofuscinosis type 2 (CLN2) is a rapidly progressive neurodegenerative disorder leading to premature mortality. Ambulatory CLN2 patients typically receive standard of care treatment through biweekly intracerebroventricular (ICV) enzyme replacement therapy (ERT) involving recombinant human tripeptidyl peptidase 1, known as cerliponase alfa (Brineura^®, Biomarin Pharmaceuticals). This study longitudinally assessed the impact of ICV cerliponase alfa ERT on gait, and postural control across a two-year span in two siblings diagnosed with atypical CLN2 disease. Both participants, ID01 (18 years and 8 months old at enrollment) and ID02 (13 years and 3 months old at enrollment), exhibited symptomatic characteristics …

Modulation Of Stemness And Differentiation Regulators By Valproic Acid In Medulloblastoma Neurospheres, Natália Hogetop Freire, Alice Laschuk Herlinger, Julia Vanini, Matheus Dalmolin, Marcelo A C Fernandes, Carolina Nör, Vijay Ramaswamy, Caroline Brunetto De Farias, André Tesainer Brunetto, Algemir Lunardi Brunetto, Lauro José Gregianin, Mariane Da Cunha Jaeger, Michael D Taylor, Rafael Roesler

Faculty, Staff and Students Publications

Changes in epigenetic processes such as histone acetylation are proposed as key events influencing cancer cell function and the initiation and progression of pediatric brain tumors. Valproic acid (VPA) is an antiepileptic drug that acts partially by inhibiting histone deacetylases (HDACs) and could be repurposed as an epigenetic anticancer therapy. Here, we show that VPA reduced medulloblastoma (MB) cell viability and led to cell cycle arrest. These effects were accompanied by enhanced H3K9 histone acetylation (H3K9ac) and decreased expression of the MYC oncogene. VPA impaired the expansion of MB neurospheres enriched in stemness markers and reduced MYC while increasing TP53 …

Insights Into Rett Syndrome: Social Behavior, Bdnf-Trkb Signaling, And Dendritic Spines, Destynie Medeiros

All ETDs from UAB

Rett syndrome (RTT) is a neurodevelopmental disorder primarily affecting females, caused by pathogenic variants in the X-linked MECP2 gene, which encodes the transcriptional modulator Methyl-CpG binding protein 2 (MeCP2). RTT is characterized by motor deficits, loss of speech, autistic features, and intellectual disability. A key gene regulated by MeCP2 is BDNF, encoding the neurotrophin brain-derived neurotrophic factor (BDNF). BDNF levels are lower in multiple brain regions of Mecp2-deficient mice, and experimentally increasing BDNF levels improves several RTT phenotypes in mouse models. Due to BDNF's low blood-brain barrier permeability, we tested LM22A-4, a brain-penetrant small molecule ligand of TrkB receptors, on …

Neural Mechanisms Of Proactive And Reactive Cognitive Control In Humans, Anas Khan

All ETDs from UAB

Cognitive control enables flexible, goal-directed behavior by dynamically adjusting our actions in response to changing task demands. This dissertation investigates the neural mechanisms underlying proactive and reactive cognitive control, particularly focusing on the dorsolateral prefrontal cortex (dlPFC) and the dorsal anterior cingulate cortex (dACC) during tasks that require response inhibition and conflict processing. Using intracranial electroencephalography (iEEG) recordings from human participants, this research examines the distinct roles of oscillatory activity in these regions in both short-term reactive adjustments and long-term proactive control strategies. Chapter 2 explores the role of low-frequency oscillations in the mid-rostral dlPFC during motor inhibition, revealing that …

The Dopaminergic Cell-Intrinsic Clock And Bidirectional Relationships Of Circadian Disruption And Synucleinopathy, Ananya Swaroop

All ETDs from UAB

Circadian rhythms are crucial endogenous cycles with period of ~24 hours that evolved to adapt to light – dark driven changes in environmental conditions. At a molecular level, circadian rhythms are generated by the actions of clock genes that form a transcriptional- translational feedback loop and regulate the rhythmic expression of downstream clock-controlled genes. Cumulatively, the actions of these molecular clocks regulate rhythmicity of physiological and behavioral processes and are extensively characterized within the central circadian pacemaker, the suprachiasmatic nucleus (SCN). Like SCN neurons, dopaminergic neurons of the SN are intrinsically pacemaking, though it is unknown if this intrinsic firing …

Social Dominance And Cortical Neuronal Synchrony In Male Mecp2 Knockout Mice, Cesar Andres Acevedo Triana

All ETDs from UAB

Social behaviors are critical for the survival of individuals, and their dysfunction is common in several neuropsychiatric and neurodevelopmental disorders including autism, where impaired sociability is one of the core diagnostic symptoms and compromises the interpretation of social cues, with an apparent lack of interest in others. Among the neurodevel opmental disorders associated with autism, Rett syndrome (RTT) is a disorder predominantly affecting females and caused by spontaneous loss-of-function mutations in the X-linked MECP2 gene, which encodes the transcriptional regulator MeCP2 that regulates many critical genes. RTT individuals have impaired motor, cognitive, and social abilities most of which are recapitulated …

Optimizing Electrode Configurations For Eeg Mild Cognitive Impairment Detection, Yi Jiang, Xin Zhang, Zhiwei Guo, Xiaobo Zhou, Jiayuan He, Ning Jiang

Faculty, Staff and Student Publications

The Optimal electrode configuration of Electroencephalograms (EEG) systems for mild cognitive impairment (MCI) detection and monitoring in non-clinical settings, i.e. number of electrodes and the positions of the electrodes, remains to be explored. In the current study, we explored the optimization of electrode configuration for MCI detection. We used a 32-channel EEG device to record the data of 21 MCI patients and 20 cognitively normal elderly (NC) undergoing working memory (WM) tasks. Based on the differential value (MCI group vs. NC group) from the Power Spectral Density (PSD) value of each electrode in θ and α frequency band during WM …

Minimally Invasive Non-Expansile Tubular Extradural Posterior Fossa Decompression (Minted Technique) For The Management Of Chiari I.5 Malformation: Historical Overview Of Surgical Techniques, Technical Note, Proof Of Concept, Illustrative Case And Case Series. Lesser Is Better, José Alberto Israel Romero Rangel, Manuel Eduardo Soto García, Sergio Soriano Solís, Carlos Raúl Rangel Morales, Gerson Reyes Rodríguez, José Antonio Soriano Sánchez

Archives of Neurosurgery

BACKGROUND: Chiari's Malformation surgical treatment has significantly changed since the "classical" technique description by Gardner (1950). It is probably the most commonly performed approach, even when multiple techniques are available because no substantial changes nor any clear surgical objectives have been made. OBJECTIVE: To demonstrate a new cutting-edge surgical technique mastering the advantage of each surgical procedure ever described in the history of Chiari's Malformation establishing three critical points in surgical technique: clear patient-specific surgical goals, dynamic posterior fossa reconstruction, and extradural occipitoatlantal dense-adhesions release. METHODS: A comprehensive review of historically described approaches, proof of concept of surgical technique in …

High-Grade Avm. Educational Vignette And Clinical Cases, Marcos Devanir Silva Da Costa, Marcelo Augusto Acosta Goiri, Daniela Coelho, Juan Alberto Paz Archila, Talita Helena Martins Sarti, Feres Chaddad-Neto

Archives of Neurosurgery

The arteriovenous malformation (AVM) is a vascular malformation characterized by fistulas between arteries and veins forming a nidus, without interposition of capillary vessels and of which early draining vein is identified at the digital angiography. Potential reports of its existence date from the second century AD. Spetzler and Martin (S-M) proposed a classification considering three features and Lawton then added new predictors. A maximum of 10 score can be achieved by applying the modified S-M grade system. This classification guides decision-making and the possible choice of the multimodal treatment (surgery, radiosurgery and embolization). We discuss historical, pathological, clinical and therapeutic …