Neurosciences Commons^™

Clinical And Imaging Correlates Of Cognitive Impairment Patterns In Early Unilateral Brain Injury Associated With Sturge-Weber Syndrome, Halah Keramane, Csaba Juhasz Md, Phd, Michael E. Behen Phd, Aimee Luat Md

Medical Student Research Symposium

Background: Sturge-Weber syndrome (SWS) is a rare neurocutaneous disease characterized by cerebral venous malformations leading to early damage of affected brain regions. Clinical symptoms include seizures, motor and cognitive impairment. Most SWS patients have unilateral brain involvement, and previous studies reveal substantial neurological plasticity in some of them. Some children with left-hemispheric damage demonstrate, paradoxically, preserved verbal functions and reduced nonverbal functions (a “crowding” effect), suggesting contralateral functional reorganization from damaged cortical regions. We evaluated the incidence as well as clinical and imaging correlates of such functional reorganization/crowding.

Methods: Forty-six patients (age: 2.5-24 years) with unilateral SWS underwent neurocognitive evaluations …

Assessing Platelet Counts As Predictors Of Vasospasm And Discharge Outcomes In Aneurysmal Subarachnoid Hemorrhage, Alexander Weiss M.S., B.S., B.A., Jared C. Reese M.D., Pouya Entezami M.D., M.S.

Medical Student Research Symposium

Introduction: Aneurysmal subarachnoid hemorrhage (aSAH) carries a 21.9% 30-day case fatality rate, largely due to complications from cerebral vasospasm (CVS), which can lead to delayed cerebral ischemia (DCI). Despite extensive research, the best predictive biomarkers for vasospasm remain unclear. This study evaluates whether variations in platelet count predict vasospasm and patient outcomes in aSAH.

Methods: A retrospective cohort study included 297 aSAH patients from the Henry Ford Health System electronic medical records. Inclusion criteria required an aSAH diagnosis, hospital admission within 24–48 hours of symptom onset, transcranial Doppler (TCD) data, daily platelet count, and modified Rankin scale (mRS) …

Environmental Pollution And Early-Life Metabolic Programming, Lisa Koshko

Wayne State University Dissertations

Substantial evidence demonstrates that parental pollutant exposures can induce harmful health effects in the offspring, including the predisposition to Type II Diabetes. As rates of Type II Diabetes continue to rise in younger populations, a crucial gap lies in understanding the role of parental influence in the etiology of later-life metabolic disease. Therefore, the central goal of this work was to determine how early life exposure to smoking level benzene, an endocrine-disrupting air pollutant, affects the metabolic health of offspring, and to identify potential developmental mechanisms involved in disease susceptibility. This goal was achieved using two models of early life …

Neural Correlates Of Fear Extinction: Investing The Impact Of Puberty And Sex In Children And Adolescents Through Neuroimaging, Sneha Bhargava, Clara Zundel, Samantha Ely, Carmen Carpenter, Reem Tamimi, Leah Gowatch, Mackenna Shampine, Emilie-Clare O'Mara, Jovan Jande, Shravya Chanamolu, Ahmad Almaat, Hilary Marusak

Medical Student Research Symposium

Fear-based disorders, including anxiety and posttraumatic stress disorder, are more prevalent in females than males. Steroid hormones (e.g., estradiol) are involved in fear extinction learning and later recall—a process implicated in the pathophysiology of fear-based disorders. Fear-based disorders commonly emerge during the transition from childhood to adolescence, a period marked by the onset of puberty and a natural increase of steroid hormones. Here, we examined the effects of puberty, sex, and their interaction on extinction recall and underlying neural circuitry in youth. Eighty-five youth (6-17 years, 46% female) completed a two-day Pavlovian fear extinction paradigm while undergoing functional magnetic resonance …

Epithelial And Mesenchymal Olfactory Stem Cells Gathered With Minimally-Invasive Micro-Brush, Tyler Petersen

Medical Student Research Symposium

Spinal cord injury (SCI) causes devastating lifestyle and financial consequences for the patient. Treatment strategies emphasize neuroprotection, but not regeneration. In this regard, stem cells are an innovative field of study that has the potential to regenerate neural tissue, thereby increasing a person’s ability to regain function. The purpose of this project is two-fold: to attain olfactory stem cells located in the nasal canal in a minimally-invasive way and to gather neural cells from the epithelium and mesenchymal cells in the lamina propria. Cells were gathered with sterile nasal micro-brushes, stored, and grown in flasks. After cells reached confluency, they …

Age-Related Longitudinal Changes In Gray Matter Microstructure, Jessica Hayes

Wayne State University Theses

Measures of the brain’s microstructure may be more sensitive markers of aging than macrostructural measures. However, it remains unclear exactly how gray matter microstructure changes during aging and how this relates to changes in macrostructure. The present study evaluated how neurite density, orientation dispersion, and gray matter volume changed over a three-year period in a sample of healthy older adults. The role of age in modifying structural change within the hippocampus, precuneus, and rostral anterior cingulate cortex was also considered. Repeated measures general linear models additionally evaluated whether degree of change in microstructure between the first two measurement occasions modified …

Plasma Neurofilament Light As A Biomarker Of Neurodegeneration And Memory Function In Older Adults, Youjin Jung

Wayne State University Dissertations

Plasma neurofilament light (NfL) is a promising biomarker for monitoring and predicting cognitive function and neurodegeneration in Alzheimer’s disease (AD). However, the field still needs a better understanding of what plasma NfL reflects about neurodegenerative and cognitive changes occurring in AD, especially in the early stages of Alzheimer’s disease, for the optimized use of plasma NfL as a biomarker for AD for clinical and research purposes. Therefore, here I investigated how NfL is associated with memory function, the functional connectivity of the default mode network, and the microstructural properties of white matter and gray matter regions vulnerable to Alzheimer’s pathologies …

Hippocampal Subfield Volumes And Memory Development From Middle Childhood To Late Adulthood: 2-Year Longitudinal Change And Modifiers Of Age Effects, Roya Homayouni

Wayne State University Dissertations

Introduction: The hippocampus (Hc) is crucial for memory function across all ages and is comprised of distinct subfields: dentate gyrus (DG), cornu ammonis sectors (CA1-3), and subiculum. Hc subfields support different aspects of memory function across the lifespan and are differentially vulnerable to late-life pathology. Increased knowledge of normative lifespan developmental trajectories of Hc subfield volumes will illuminate their cognitive and health correlates across different ages. Yet, the evidence on change and variability of Hc subfield volumes across the lifespan is sparse. Methods: Here, I conducted a meta-analysis of cross-sectional findings of subfield volumes across ages (n = 48,278 participants, …

Intravital Imaging Of Cellular Response Due To Traumatic Brain Injury Using Confocal Microscopy, Enoch G. Kim, Jeffrey Horbatiuk, Carolyn Harris

Medical Student Research Symposium

Introduction: Cellular reaction to traumatic brain injury is complex and involves considerable interactions between cells and reactivity to foreign bodies. Our objective was to assess neurons, microglia, astrocytes, and intracellular Ca²⁺ signaling by creating a novel confocal microscopy technique involving an air immersed lens that does not sacrifice resolution and limits signal attenuation. This study aimed to create a consistent dynamic methodology to observe the cortical cellular response using real-time intravital imaging as trauma is being induced.

Methods: Once surgical plane was achieved, rodent cortices were exposed via craniotomy and blunt insertion with a silicone shunt catheter into the …

Neural Correlates Of Memory Formation Of Young Children In A Term And Preterm Born Sample, Christina Lee

Wayne State University Theses

Episodic memory facilitates the ability to encode and retrieve information. This is especially important when considering special populations, such as children born prematurely, who are at high risk of developing deficits in episodic memory. Utilizing functional magnetic resonance imaging (fMRI), the current study aimed to examine differences between activations of neural correlates (MTL, PFC) of episodic memory compared to activations in a control region, the primary visual cortex (BA17) in children born full-term and preterm. More specifically, differences during memory encoding and subsequent memory effects (SMEs) were investigated. The MTL, PFC, and BA17 regions showed encoding activation while participants were …

Meta-Analysis Of 175 Patients With Covid-19 And Seizures, Status Epilepticus, Or Cortical Myoclonus: An Individual Patient Data Analysis, Aditi Kappagantu Bs, Helena A. Brantz Ms, Amman Bhasin Ba, Cristina Jageka Bs, Rooqash Ali Md, Izzy Saef Md, Brittany M. Stopa Mph, Ayaz Khawaja Md

Medical Student Research Symposium

Objective

To characterize management and outcomes of seizures, status epilepticus, and cortical myoclonus in COVID-19, with individual patient data analysis of published literature.

Methods

Systematic literature review was conducted in accordance with PRISMA guidelines. Criteria included new-onset seizures, status epilepticus, and/or cortical myoclonus with concomitant COVID-19. COVID-19 severity was dichotomized into mild and severe cases. Good outcome was defined as discharge without severe deficits, and/or return to baseline.

Results

A total of 105 studies reporting 176 patients (male 56.3%;mean age 47.8,SD 25.6) were included. Status epilepticus occurred in 47 patients (26.7%) and myoclonus in 41 (23.3%). Severe COVID-19 occurred in …

Norepinephrine Regulation Of Spatial Memory Using The Barnes Maze In Male And Female Rats, Serena Simpson, Ali Gheidi Phd, Nareen Sadik, Cameron J. Davidson Phd, Shane A. Perrine Phd

Medical Student Research Symposium

The role of norepinephrine (NE) in learning and memory has been extensively studied, yet its contribution remains to be clarified. This study aimed to investigate the role of NE on spatial learning and memory in female and male rats using a Barnes maze assay. We used N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4), a specific noradrenergic neurotoxin that can cross the blood brain barrier, to deplete NE stores. We hypothesized that brain NE ablation would attenuate spatial learning and memory in rats. Loss of NE by DSP-4 was determined by measuring NE (and dopamine and serotonin) levels in several brain regions using HPLC. For the …

Intrabody-Mediated Postsynaptic Recruitment Of Camkiiα Improves Memory, Anthony Chifor, Jeongyoon Choi Dr., Joongkyu Park Dr.

Medical Student Research Symposium

Long-term potentiation (LTP), the selective strengthening of specific synapses based on recent activity, has widely been accepted as the biological mechanism responsible for learning and memory. N-methyl-D-aspartate receptors (NMDARs) play a critical role in LTP, which when activated, result in a surge of postsynaptic intracellular calcium levels. The calcium rise during LTP results in the activation of Ca²⁺/calmodulin-dependent kinase II alpha (CaMKIIa), which consequently enacts multiple cellular effects that ultimately result in the strengthening of synaptic connections. Previous work has examined the effects of CaMKIIa overexpression in rat hippocampi on spatial memory, however, significant but limited improvement in …

The Importance Of Protein Context In Spinocerebellar Ataxia Type 3, Sean Luis Johnson

Wayne State University Dissertations

Spinocerebellar Ataxia Type 3 (SCA3) is a member of the family of polyglutamine (polyQ) neurodegenerative disorders that includes Huntington's Disease and several other SCAs. SCA3, the most common dominant ataxia in the world, is caused by polyQ tract expansion in the protein, ataxin-3. How SCA3 occurs and how to treat it remain unresolved issues. The primary culprit of toxicity in all polyQ diseases is the glutamine repeat: its abnormal expansion leads to neuronal dysfunction and death. With that said, there is indisputable evidence that the way polyQ-dependent toxicity presents—areas impacted, cellular processes perturbed—is predicated in large part on regions outside …

Backward Walking: A Novel Marker Of Fall Risk, Cognitive Dysfunction, And Myelin Damage In Persons With Multiple Sclerosis, Erin Edwards

Wayne State University Dissertations

Multiple sclerosis (MS) is a progressive, neurologic disease of the central nervous system that causes debilitating motor, sensory and cognitive impairments. As a result, persons with MS are at an increased risk for falls and falls represent a serious public health concern for the MS population. The current clinical measures used to assess fall risk in MS patients lack sensitivity and predictive validity for falls and are limited in their ability to capture to multiple functional domains (i.e., motor, sensory, cognitive and pathological domains) that are impaired by MS. Backward walking sensitively detects falls in the elderly and other neurologic …

Dancing The Storm: Neurobiological Correlates Of Trauma-Related Psychopathology In Youth Resettled As Refugees, And The Efficacy Of Creative Arts And Movement Therapies To Address Trauma-Related Psychopathology, Lana Ruvolo Grasser

Wayne State University Dissertations

Exposure to stress and trauma activates key adaptive pathways, including the sympathetic adrenomedullary system and the immune system, which can result in long-term health impacts of trauma especially when experienced during sensitive developmental periods. Alterations in these systems are measurable through non-invasive methods including skin conductance response (SCR), fear potentiated startle (FPS), and inflammation. Research regarding the impact of trauma, and more specifically posttraumatic stress disorder, has primarily focused on adults, and there is a paucity of neurobiological research in displaced populations—like refugees—who may experience higher rates of trauma exposure and related psychopathology. The present study measured SCR to a …

Characterization Of Abin-1 In The Traumatically Injured Brain, Aaron Orellana, Alana C. Conti

Medical Student Research Symposium

Traumatic brain injury (TBI) is associated with chronic pain and persistent neuroinflammation. Opioids are often prescribed in order to relieve pain symptoms, but recent evidence suggests that their use negatively impacts the neuropathology of TBI leading to behavioral impairments and exacerbated neuroinflammation. The de-ubiquinating enzyme tumor necrosis factor alpha-induced protein (TNFAIP)3 or A20, inhibits the inflammatory signaling transcription factor nuclear factor (NF)-kB leading to attenuation of the inflammatory response. A20-binding inhibitor of nuclear factor kB (ABIN-1), which physically interacts with A20, also plays a role in the inhibition of NF-kB and is poorly researched in the central nervous system (CNS). …

Oral Cbd Administration: Assessing Bioavailability And Behavioral Outcomes In A Rodent Model, Jordan Skully

Wayne State University Theses

There has been a recent surge in popularity for cannabidiol (CBD), a major non-psychotropic constituent of cannabis, due to numerous claims of potential therapeutic properties, which include, but are not limited to, anxiolytic, antinociceptive, and anti-inflammatory effects. However, as previous scientific literature on CBD's effectiveness in providing such therapeutic effects is limited, this project was aimed to evaluate the potential beneficial properties of a hemp derived 99% pure CBD compound provided from Ellipse Analytics (Denver, CO) in a rodent model. We analyzed the pharmacokinetics of this CBD product as well as the behavioral outcomes after acute and chronic administration. Pharmacokinetics …

Modulation Of Pharyngeal Health In Bacterial Diet-Dependent Survival, Deniz Sifoglu

Wayne State University Dissertations

ABSTRACT

MODULATION OF PHARYNGEAL HEALTH IN BACTERIAL DIET-DEPENDENT SURVIVAL

by

DENIZ SIFOGLU

August 2021

Advisor: Dr. Joy Alcedo Major: Biological Sciences Degree: Doctor of Philosophy Both diet and bacterial microbiome modulate insulin signaling, which regulates key physiological processes that are important for survival. However, the mechanisms through which diet and the microbiome modulate insulin signaling remain unclear. To understand these mechanisms, I turned to the nematode worm C. elegans, whose diet consists of different types of bacteria. Like humans and other animals, C. elegans has to modulate its responses to its diet and to bacteria to optimize its survival. Because …

Hypochlorite-Mediated Oxidation Of Dopamine: Implications In Parkinson’S Disease And Manganism, Praneet Kaur Marwah

Wayne State University Dissertations

Both Parkinson’s disease and manganism (a condition caused by chronic exposure to excessive levels of manganese) affect the extrapyramidal system of the brain, disrupt dopaminergic signaling and cause similar motor symptoms. While there is no physiological explanation for the susceptibility of dopamine-rich regions of the brain in both disorders, dopamine itself is a likely candidate. Dopamine can undergo both enzymatic and spontaneous oxidation, and the principal product of dopamine oxidation in vivo is cysteinyl dopamine. We demonstrate here that hypochlorous acid, which is produced in the brain by the enzyme myeloperoxidase, converts cysteinyl dopamine into a neurotoxic dihydrobenzothiazine, DHBT-1, that …

Quench Assisted (Quest) Mri Used As A Novel Approach To Identify Reactive Oxygen Species As A Result Of Experimental Tbi, Ethan M. Cohen, Eric Chang, Michael C. Schneider, Abigail Teitelbaum, Alexander R. Woznicki, Rachel E. Godfrey, Robert H. Podolsky, Karen L. Childers, Robin Roberts, Bruce A. Berkowitz, Kelly E. Bosse, Alana C. Conti

Medical Student Research Symposium

Introduction:

Traumatic brain injury (TBI) generates reactive oxygen species (ROS), promoting inflammatory processes and impeding TBI recovery. Within the VA population, over 70% of military personnel that sustain a TBI receive opioid-based pain relief, however, opiates may actually exacerbate post-TBI complications through its documented recruitment of oxidative and inflammatory systems. Thus, we hypothesize that TBI and opioid treatment act synergistically to worsen post-TBI oxidative stress.

Methods:

Mice were exposed to either TBI or sham injury and administered morphine or saline in the acute post-injury period. Afterwards, neuroimaging was conducted using a novel technique, QUEnch assiSTed (QUEST) MRI, which compares standard …

Investigating Gray And White Matter Microstructure In Parkinson Disease Patients Using Diffusion Weighted Imaging, Wafaa Sweidan

Wayne State University Dissertations

Parkinson disease (PD) is a neurodegenerative disorder characterized histologically by the loss of dopaminergic neurons in the substantia nigra (SN), and clinically by motor symptoms. PD pathology extends beyond the SN, and involves the presence of intraneuronal inclusions in neuronal bodies (Lewy bodies) and dendrites (Lewy dendrites). A staging system for Lewy pathology has been proposed, where it is hypothesized that the disease initiates in the peripheral nerves system and spreads along a caudal-rostral pathway to the brain stem and the cerebral cortex. Histological and imaging studies highlight a role for cortical Lewy pathology and atrophy, respectively, in mediating the …

Age Differences In Hippocampal Glutamate Modulation During Associative Learning And Memory: A Proton Functional Magnetic Resonance Spectroscopy (1h Fmrs) Study, Chaitali Anand

Wayne State University Dissertations

Episodic and associative memory decline is one of the earliest cognitive impairments in normal aging and among the defining cognitive features of Alzheimer’s disease (AD). Since, age-related cognitive decline gradually devolves into AD, with neuropathology preceding cognitive changes by many years, the identification of biomarkers of early disease progression is crucial. Reduction in glutamate, the main excitatory neurotransmitter involved in associative memory, in key brain regions such as the hippocampus, has been theorized as one of the cellular mechanisms underlying cognitive decline in aging and AD. A few neuroimaging studies that demonstrated a link between older adults’ weaker cognitive performance …

Characterizing The Development Of Episodic Memory And Assessing The Reliability Of Fmri Measures, Lingfei Tang

Wayne State University Dissertations

The ability to remember past events is critical for everyday life and showed robust improvement over development from childhood to adulthood. With advances in noninvasive neuroimaging methods such as functional MRI in recent years, research efforts have been focused on identifying neural correlates underpinning developmental gains in memory performance. In my dissertation work, using a widely-validated subsequent memory paradigm, I aim to characterize functional MRI correlates of memory development. Specifically, I focused my investigation on identifying age differences in the functional patterns of two brain regions critical for memory, the prefrontal cortex and the hippocampus. Focusing on the prefrontal cortex …

Development Of More Light Sensitive And Red-Shifted Channelrhodopsin Variants For Optogenetic Vision Restoration, Tushar Harishkumar Ganjawala

Wayne State University Dissertations

Discovery of channelrhodopsin (ChR), a light sensitive protein from green algae, has revolutionized the field of neuroscience research by empowering scientist to control neuron through the light, the technology popularly known as optogenetics. The ChR based optogenetics is one of the promising approaches for treating blindness caused by photoreceptor degenerative diseases such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD). Fundamentally, the approach is about imparting light sensitivity to surviving inner retinal cells by ectopic expression of genetically encoded light sensitive proteins, such as ChR2. Although the concept of optogenetic approach has been proved by using ChR2, a major …

Stress-Dependent Regulation Of A Major Node Of The Insulin-Like Peptide Network That Modulates Survival, Rashmi Chandra

Wayne State University Dissertations

Chronic stress disrupts insulin signaling, predisposing human populations to diabetes, cardiovascular disease, Alzheimer’s Disease, and other metabolic and neurological disorders, including post-traumatic disorders (PTSD). Thus, efficient recovery from stress optimizes survival. However, stress recovery in humans is difficult to study, but is much easier to dissect in model organisms. The worm genetic model Caenorhabditis elegans can switch between stressed and non-stressed states, and this switch is largely regulated by insulin signaling. Previously, the Alcedo lab proposed that insulin-like peptides (ILPs), which exist as multiple members of a protein family in both C. elegans and humans, implements a combinatorial coding strategy …

The Impact Of Neonatal Pain And Reduced Maternal Care On Brain And Behavioral Development, Sean Michael Mooney-Leber

Wayne State University Dissertations

In the neonatal intensive care unit (NICU) preterm infants are exposed to a multitude of stressors, which include both neonatal pain and reduced maternal care. Clinical and preclinical research has demonstrated that exposure to neonatal pain and reduced maternal care has a profound negative impact on brain and behavioral development. Currently, the biological mechanism by which both of these stressors impacts brain and behavioral outcomes remains widely unknown. To uncover a potential biological mechanism, the current dissertation project utilized a preclinical model of repetitive needle pokes and developed a novel model of reduced maternal care through tea-ball encapsulation. Briefly, rat …

The Influence Of Protein Context On Polyglutamine Toxicity In Spinocerebellar Ataxia Type 3, Joanna Rae Sutton

Wayne State University Dissertations

The polyglutamine (polyQ) disease family is composed of nine neurodegenerative diseases caused by CAG trinucleotide repeat expansions in the associated genes. Although these diseases are caused by similar mutations, the polyQ proteins are otherwise structurally and functionally unique. Thus, the protein domains surrounding the polyQ tracts, as well as their interacting partners, are thought to be critical to the pathogenesis of these clinically distinct diseases. Spinocerebellar ataxia type 3 is caused by polyQ expansion of ataxin-3, a deubiquitinating enzyme implicated in protein quality control, transcriptional regulation, and DNA repair. Rad23 and VCP are two of ataxin-3’s protein quality control partners …

Proteolipid Protein 1 Regulates Inflammation In The Central Nervous System, Whitney Hoff

Wayne State University Theses

Pelizaeus-Merzbacher disease (PMD) results from mutations in the proteolipid protein 1 (PLP1) gene including PLP1 duplications and deletions. The absence of PLP is preferable to PLP1/Plp1 duplication in PMD patients and rodents as lifespan of PLP1/Plp1 null mammals is nearly normal. The reason for this is not entirely understood. However, because of this, less attention has been placed on Plp1 null mutations than on classical PMD mutations. However, data show that PLP levels must be properly titrated to ensure normal brain function. Specifically, changes in PLP1/Plp1 expression can result in massive microglia activation in animal models of PMD and likely …

Non-Invasive Mitochondrial Modulation With Near-Infrared Light Reduces Brain Injury After Stroke, Christos Dionisos Strubakos

Wayne State University Dissertations

Acute ischemic stroke is a debilitating disease that causes significant brain injury.

While rapid restoration of blood flow is critical to salvage the ischemic brain, reperfusion

of tissue can further drive brain damage by inducing generation of mitochondrial reactive

oxygen species (Chouchani et al., 2014a). Recent studies by our group found that noninvasive

mitochondrial modulation (NIMM) with near-infrared (NIR) light can limit the

production of reactive oxygen species following global brain ischemia (T. H. Sanderson

et al., 2018). NIR interacts with the rate limiting step of the mitochondrial electron

transport chain (ETC), cytochrome c oxidase (COX), and modulates mitochondrial

respiration. …