Neurosciences Commons^™

Extracellular Vesicle-Mediated Transfer Of Gsdme-Nt Pores As A Mechanism Of Inflammation Propagation, Bifeng Xiao

Master's Theses

Inflammasomes are multiprotein complexes that initiate inflammatory signaling through activation of caspase-1, cytokine maturation, and cleavage of Gasdermin D (GSDMD). Cleaved GSDMD forms membrane pores that contribute to cytokine release and pyroptotic cell death. Recent evidence suggests that extracellular vesicles (EVs) may facilitate the intercellular transfer of inflammatory mediators. This study investigated whether GSDMD N-terminal fragment (GSDMD-NT) associates with EV-enriched fractions and contributes to inflammation propagation. Doxycycline-inducible HeLa cells expressing FLAG-tagged GSDMD-NT were used to generate EV-enriched fractions. Western blot analysis detected GSDMD-NT-associated material within EV fractions, while EV marker analysis supported successful enrichment of EV-associated material. Exposure of recipient …

Cognitive Decline In Dutch-Type Hereditary And Sporadic Cerebral Amyloid Angiopathy: A 5-Year Follow-Up Study, Rosemarie Van Dort, Vera C.J. Van Stek-Smits, Sanne E. Schriemer, Reinier G.J. Van Der Zwet, Manon R. Schipper, Sabine Voigt, Ellen P. Hart, Vandhana Easwaran, Hamid R. Sohrabi, Kevin Taddei, Samantha L. Gardener, Ralph N. Martins, Steven M. Greenberg, Matthias J.P. Van Osch, Marianne A.A. Van Walderveen, Marieke J.H. Wermer, Ellis S. Van Etten

Research outputs 2022 to 2026

Introduction: Cerebral amyloid angiopathy (CAA) is associated with cognitive impairment, but its longitudinal course of cognitive decline remains unclear. We investigated domain-specific cognitive trajectories in Dutch-type hereditary (D-CAA) and sporadic CAA (sCAA) to compare patterns and rates of decline. Methods: We included 181 participants – 93 D-CAA mutation carriers (59 without, 34 with prior intracerebral hemorrhage [ICH]) and 88 with sCAA (57 without, 31 with ICH) – who underwent annual neuropsychological assessment. Longitudinal change in global cognition, memory, processing speed, and executive function was analyzed using linear mixed models. Results: Over 5 years, cognitive decline was subtle but measurable. Memory …

Neuroprotective Effects Of Sorghum Polyphenol In Alzheimer’S Disease: In Vitro And In Silico Analyses, Rasheed A. Abdulraheem, Ralph N. Martins, Rajapandiyan Krishnamoorthy, Mohammad A. Alshuniaber, Prashant Bharadwaj, Zhaoyu Li, Ranil Coorey, Vijay Jayasena, Stuart K. Johnson, W. M.A.D.Binosha Fernando

Research outputs 2022 to 2026

Background/Objective: Accumulation of amyloid-beta (Aβ) senile plaques in the human brain is a major hallmark of Alzheimer’s disease (AD), which manifests as progressive decline in memory and cognitive functions and currently lacks effective disease-modifying therapies. Emerging evidence demonstrates that polyphenol-rich plant foods are potential complementary therapies for AD. Methods: In this study, we investigated crude polyphenol extracts (CPEs) and purified polyphenol extracts (PPEs) from three sorghum genotypes for their ability to inhibit Aβ42-induced toxicity in MC-65 cells. Thioflavin T fluorescence, cell viability, mitochondrial function, oxidative stress assays, and Western blotting, along with RNA sequencing and computational analyses, were used to …

Peripheral Nerve Sensory Fibers Are Recruited With Less Current And Greater Selectivity By Conventional Waveforms Compared With High-Frequency Waveforms, Janie Provencher, Harrison T. Finn, Janet L. Taylor, Simon C. Gandevia, Jane E. Butler, Martin E. Héroux

Research outputs 2022 to 2026

Transcutaneous spinal stimulation aims to target dorsal spinal roots, which deliver sensory information to the spinal cord. However, the stimulation waveform that most effectively recruits sensory fibers at the lowest intensity has not been identified. The purpose of this study was to compare conventional and high-frequency burst-modulated stimulation waveforms in their ability to recruit sensory fibers, as assessed by H-reflex threshold, recruitment characteristics, and motor fiber activation. In participants with intact neurological function (n ¼ 12), soleus H-reflex recruitment curves were recorded for 10 stimulation waveforms: a conventional waveform (400 μs), serving as the reference condition, high-frequency burst-modulated waveforms (2, …

The Poly-Arginine Peptide R18d Inhibits Amyloid-Beta (Aβ) Aggregation And Aβ-Induced Cytotoxicity, Reduces Intracellular Tau Aggregation, And Exhibits Oral Bioavailability, Vaishali Bagda, Zainab H. Farooz, Neville W. Knuckey, Samantha M. South, Stuart K. Gribble, Maitri Tomar, Prashant Bharadwaj, Ajish Ariyath, Kevin Taddei, Ralph N. Martins, Bruno P. Meloni

Research outputs 2022 to 2026

Background/Objectives: Effective disease-modifying therapies targeting pathogenic proteins associated with Alzheimer’s disease (AD) remain limited. This study investigated the therapeutic potential of the neuroprotective, cationic arginine-rich peptide R18D to mitigate the pathogenic effects of amyloid-beta (Aβ) and tau associated with AD.

Methods: R18D was examined for its ability to inhibit Aβ aggregation in a cell-free assay, attenuate Aβ-induced cytotoxicity in MC65 cells, and suppress intracellular tau aggregation in two neural cell models. Intracellular tau aggregation was quantified using a homogeneous time-resolved fluorescence assay. Additionally, a pilot pharmacokinetic study of R18D was conducted in mice following oral gavage administration.

Results: In the …

Antibiotic Administration After Previable Preterm Prelabor Rupture Of Membranes Is Associated With Prolonged Latency, Alexandra L Hammerquist, Alexander M Saucedo, Selina L Bowler, Mohan Pammi, Catherine Eppes, Ignatia Van Den Veyver, Michael D Jochum, Enrico R Barrozo

Duncan NRI Faculty and Staff Publications

Introduction: While antibiotics have been shown to increase the interval to delivery between rupture of membranes and delivery (latency) and improve neonatal outcomes after viable preterm prelabor rupture of membranes (PPROM), this has not been well investigated in the previable PPROM population. We aimed to investigate the association between antenatal antibiotics and latency following previable PPROM. Secondarily, we examined various maternal and neonatal outcomes. We hypothesized that the administration of antibiotics would prolong latency in pregnancies with previable PPROM.

Methods: Single-center retrospective cohort study that included pregnancies diagnosed with previable PPROM between 140/7 and 216/7 and delivered between 2012 and …

Challenge-Based Ex Vivo Immune Profiling Reveals Stimulus-Dependent Peripheral Immune Reprogramming In Alzheimer's Disease, C. A. Naranjo-Galvis, Jovanny Zabaleta, Ney Alliey Rodriguez, Luisa Matilde Salamanca-Duque

School of Medicine Publications

Altered immune function is increasingly recognized as a contributor to Alzheimer's disease (AD); however, it remains unclear whether peripheral immune alterations reflect constitutive inflammation or stimulus-dependent changes in immune responsiveness. Addressing this distinction is critical for understanding immune dysregulation in neurodegenerative diseases. In this study, we applied a challenge-based ex vivo immune profiling approach to characterize functional immune responsiveness in patients with AD and in cognitively healthy older adults. Peripheral blood mononuclear cells were exposed to defined innate, antigenic, and mitogenic stimuli, and cytokine and β-amyloid (Aβ) responses were quantified in culture supernatants. Diagnosis-by-stimulus interaction effects were assessed using generalized …

The Effects Of Anti-Parkinsonian Medications On Bone Mineral Density: A Systematic Review, Mícheál Ó Breasail, Motaz B. El-Leissy, Karan P. Singh, Matthew Smith, Jakub Mesinovic, Marc Sim, Andrew Evans, David Blacker, Saman Heshmat, Neil Mahant, Christian Girgis, Peter R. Ebeling, Ayse Zengin

Research outputs 2022 to 2026

IntroductionParkinson's disease (PD) is associated with elevated fracture risk, particularly at the hip. Antiparkinsonian medications have also been associated with increased fracture risk; although their direct effects on bone mineral density (BMD) remains unclear.ObjectiveInvestigate whether antiparkinsonian medications influence BMD.MethodsA systematic search of four databases (Embase, MEDLINE, APA PsycINFO, Web of Science) was conducted up to 24/11/2025 using terms related to PD, antiparkinsonian medications and bone.ResultsA total of 748 records were identified, with 543 screened following deduplication. Fourteen studies underwent full-text review, of which seven met inclusion criteria. Three studies assessed bone mineral content or surrogate measures at non-standard sites (hand …

Predicting Accumulation And Age At Onset Of Amyloid-Β From Genetic Risk And Resilience For Alzheimer's Disease, Eleanor K. O'Brien, Timothy Cox, Shane Fernandez, Pierrick Bourgeat, Tenielle Porter, Ben Goudey, James D. Doecke, Colin L. Masters, Jurgen Fripp, Kwangsik Nho, Victor L. Villemagne, Carlos Cruchaga, Christopher C. Rowe, Andrew J. Saykin, Vincent Doré, Simon M. Laws

Research outputs 2022 to 2026

Background: Accumulation of brain amyloid beta (Aβ), a key pathological hallmark of Alzheimer's disease (AD), begins decades before cognitive symptoms. Being able to predict the risk of Aβ accumulation, or the age at which Aβ exceeds a critical threshold, may enable intervention to delay or prevent onset of AD. Methods: Using published genome-wide association studies (GWASs), we developed polygenic scores (PGS) for AD risk (PGSrisk) and resilience (PGSresilience), and tested whether these predicted (i) if an individual is an Aβ accumulator (‘Accumulator Status’), and (ii) in accumulators, the age at which brain Aβ exceeds a 20 centiloid (CL) threshold (‘Age …

Patient Activation Measures Among Individuals With Epilepsy: A Cross-Sectional Study Of An Arabic-Speaking Population, Ghada M. Abbas, Abeer A. Khoja, Haythum O. Tayeb, Nagham S. Alsolaimani, Ibrahim M. Aldurayhim, Saher F. Alqarni

Neurosciences

Objectives: To examine patient activation levels among Arabic-speaking adults with epilepsy and to explore their associations with selected clinical and sociodemographic variables.

Methods: We conducted a cross-sectional study of 109 adult patients with confirmed epilepsy between December 2023 and October 2025. Data were collected during outpatient clinic visits, with additional information obtained through telephone contact when necessary. A sample size estimate indicated that at least 96 participants were required to achieve 80% statistical power. Patient activation was assessed using the validated Arabic version of the 13-item Patient Activation Measure (PAM-13). The variables examined included seizure type, medication regimen (monotherapy versus …

Antiseizure Drug Adherence In Pediatric Patients With Epilepsy And The Associated Factors In Saudi Arabia, Ola A Shawky, Shaima A Althoubaiti, Reham M Alkahtani, Amirah S Alharthi

Neurosciences

Objectives: To assess the prevalence of adherence to antiseizure medications and related factors in Saudi Arabia. Pediatric epilepsy presents significant challenges to the well-being and quality of life of children. Adherence to antiseizure medication is associated with better outcomes.

Methods: This study was carried out using a cross-sectional methodology to determine the prevalence of antiseizure medication adherence among children with epilepsy aged ≤ 17 years in Saudi Arabia. Data were collected between July and September 2024 via an online self-administered questionnaire, using convenience sampling through social platforms (Telegram and WhatsApp). Medication adherence was assessed using the MMAS-8 and categorized as …

Cerebrovascular And Bleeding Outcomes Of Warfarin Versus Direct Oral Anticoagulants Therapy For Atrial Fibrillation: A Systematic Review And Meta-Analysis Of Randomized Controlled Trials, Abeer A. Alomairi, Rana Alduhaysh, Alaa Samandar, Abeer Alshehri, Ghada Alabdullah, Saud Almutairi, Faisal Althekair

Neurosciences

Objectives: To compare the effects on cerebral health in atrial fibrillation patients receiving either warfarin or direct oral anticoagulants (DOACs). Atrial fibrillation is linked to a higher likelihood of both stroke and cognitive impairment. While warfarin has historically served as the leading anticoagulant treatment, DOACs are now more frequently viewed as alternatives with an improved safety profile.

Methods: The methodology involved an extensive search of multiple databases, completed up to June 2024. This search yielded randomized controlled trials, which together enrolled over 60,000 participants between the ages of 70 and 84. The DOACs studied were dabigatran, rivaroxaban, apixaban, and edoxaban, …

A Systematic Comparative Review Of Antipsychotic Efficacy And Safety In The Treatment Of Hiccups, Omar Alshargi, Samah Alzaid, Zainab Albahouth, Muradi Hassan Albanji, Hala Makki, Rawan. F. Alboqami, Maram Al Shammari, Huda Alruwaili, Fawaz Alruwaili, Rahmah Ali Algarni, Omar Ibrahim Albahouth

Neurosciences

Objective: To evaluate and compare the safety and effectiveness of antipsychotic medications for the treatment of hiccups, thereby guiding clinicians toward evidence-based treatment guidelines. Hiccups are often benign and self-limiting; however, they can become persistent and intractable, adversely affecting the quality of life. Antipsychotics have been identified as a therapeutic option for the management of hiccups; however, the available evidence supporting their safety and efficacy has not been synthesized.

Methods: This review utilized the revised Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The Cochrane Risk of Bias Assessment Tool was modified to evaluate the quality of the …

Subliminal Priming Effects On Motor And Cognitive Performance: Pilot Evidence With Implications For Neurorehabilitation, Rehab E Aljuhni, Ghader A Alqadhi, Saud A Alhassan, Sultan A Alanazi

Neurosciences

Objective: To investigate whether subliminal priming modalities (visual, auditory, or word-based) influence motor and cognitive performance in healthy young adults, and whether these effects vary by gender.

Methods: A total of 30 healthy adults were assigned to visual, auditory, or word-based priming using single-blind, stratified randomization. Subliminal stimuli were presented for 50 ms. Motor outcomes included reaction time on dominant (RT-R) and non-dominant (RT-L) sides, comfortable and maximal walking speeds measured by the 10-Meter Walk Test (10MWT), and functional mobility assessed using the Timed Up and Go (TUG) test. Cognitive performance assessed using the Trail Making Test (TMT). Outcomes were …

Sub-Regional Motor–Somatosensory Connectivity And Lifespan Plasticity In Functional Networks, Adnan A. S. Alahmadi

Neurosciences

Objectives: To determine how cytoarchitectonically defined subdivisions of the primary motor cortex, somatosensory cortex, and supplementary motor area (SMA) reorganize their integration with large-scale brain networks during healthy aging. This study investigated the lifespan trajectories of functional connectivity within cytoarchitectonically defined subregions of the primary motor cortex, somatosensory cortex, and supplementary motor area (SMA).

Methods: We conducted a cross-sectional analysis of resting-state fMRI data from 150 healthy individuals (aged 23–80 years), stratified into young, middle-aged, and older groups. Data were sourced from the Southwest University Adult Lifespan Dataset (SALD) and analyzed between June 2024 and June 2025. Using the Jülich …

Relationships Between The Corpus Callosum Index And Current Blood Parameters And Temporal Changes In These Parameters In Patients With Multiple Sclerosis, Oruç Şahin, Muzaffer Güneş

Neurosciences

Objectives: This study aimed to investigate changes in blood parameters and examine the relationships among the corpus callosum index (CCI), plaque characteristics, and blood parameters in multiple sclerosis (MS) patients. In MS, the CCI is associated with brain atrophy and disease progression.

Methods: In this retrospective, cross-sectional study, demographic data from 103 MS patients (38 males), along with blood parameters obtained five years earlier and current values, were analyzed in relation to magnetic resonance imaging (MRI) findings. The CCI calculated from MRI scans was assessed in relation to plaque distribution and number. Statistical analyses included paired sample t tests, Wilcoxon …

Clinical Characteristics Of Multiple Sclerosis And Association Of Ms Severity With Vitamin D Level In The Madinah Region Of Saudi Arabia: A Cross-Sectional Study, Majed M. Alluqmani

Neurosciences

Objective: To determine the prevalence of multiple sclerosis (MS) in the western region of Saudi Arabia and correlate it with its predictors among a cohort of patients. The prevalence of MS is increasing in Saudi Arabia, and is attributed to various factors such as recent lifestyle changes, improved disease recognition, and parental consanguinity. Knowing the exact prevalence of the disease may enhance disease management.

Methods: This cross-sectional study was conducted among individuals diagnosed with MS at clinics in the Madinah region.

Results: The study found that the prevalence of multiple sclerosis is lower in the Madinah region. Additionally, …

The Top 50 Cited Articles In Pediatric Neurology: A Bibliometric Analysis, Anas Alyazidi, Osama Muthaffar, Ahmed Bamaga, Hebah Qashqari, Abdulmalek Alhithlool, Ahmad Alanezi, Sameer Almehmadi, Mohamed Babiker, Fahad Bashiri

Neurosciences

Objectives: To identify and analyze the most influential articles within the field of pediatric neurology through a bibliometric lens. As pediatric neurology continues to expand across subspecialties, identifying landmark studies is critical for understanding clinical and research priorities. Bibliometric analysis enables the evaluation of citation trends to highlight impactful contributions that have shaped the field.

Method: A bibliometric analysis of the 50 most-cited pediatric neurology articles was conducted. Articles were assessed by citation metrics, study design, subspecialty, journal impact factor (JIF), and funding status. Correlation and regression analyses evaluated associations between variables.

Results: Citation counts ranged from 185 to 1,440 …

Prevalence Of Depression Among Patients With Epilepsy In Saudi Arabia: A Nationwide Systematic Review And Meta-Analysis, Mothana Y. Al Jabr, Aryam M. Alenizi, Faisal S. Aleisa, Mazen A. Alghamdi, Noura I. Alfehaid, Muteb M. Alqahtani, Abbas S. Almutair

Neurosciences

Objective: To assess the pooled prevalence of depression among epilepsy patients and find the associated demographics and psychosocial factors. Mood disorders are significant comorbidity between patients diagnosed with epilepsy, adversely influencing quality of life and complicating disease management. However, the incidence, prevalence, and associated risk factors of depression in patients diagnosed with epilepsy in Saudi Arabia are not well elucidated.

Methods: This review was employed used studies retrieved from medical databases and the Saudi Digital Library. Observational and cross-sectional studies assessing depression between patients diagnosed with epilepsy in Saudi Arabia were included. Data were analyzed using the Freeman–Tukey double arcsine …

Wearable Sensor Technology And Biomechanical Gait Analysis In Post-Stroke Rehabilitation: A Review With Implications For The Saudi Healthcare System, Abdullah H. Alzahrani

Neurosciences

Stroke remains a major cause of disability worldwide, with gait impairment affecting up to 80% of survivors and contributing to long-term dependence, fall risk, and reduced quality of life. In Saudi Arabia, stroke incidence is rising, with a significant burden on younger populations and disparities in access to post-stroke rehabilitation services. Conventional gait analysis tools rely on expensive, specialized laboratory equipment, which limits their availability in low-resource and rural settings. Recent advances in wearable sensor technologies, including inertial measurement units, pressure insoles, and electromyography systems, offer portable, scalable, and cost-efficient options for assessing gait in real-world environments. These systems can …