Medical Neurobiology Commons^™

Precision Medicine Approach To Alzheimer’S Disease: Rationale And Implications, Dale E. Bredesen, Kat Toups, Ann Hathaway, Deborha Gordon, Henrianna Chung, Cyrus Raji, Alan Boyd, Benjamin D. Hill, Sharon Hausman-Cohen, Mouna Attarha, Won Jong Chwa, Alexei Kurakin, Michael Jarrett

University Faculty and Staff Publications

The neurodegenerative disease field has enjoyed extremely limited success in the development of effective therapeutics. One potential reason is the lack of disease models that yield accurate predictions and optimal therapeutic targets. Standard clinical trials have pre-determined a single treatment modality, which may be unrelated to the primary drivers of neurodegeneration. Recent proof-of-concept clinical trials using a precision medicine approach suggest a new model of Alzheimer’s disease (AD) as a chronic innate encephalitis that creates a network insufficiency. Identifying and addressing the multiple potential contributors to cognitive decline for each patient may represent a more effective strategy. Here we review …

Examining A Blood Biomarker Approach To Blood-Brain Barrier Disruption, Samantha Ford

Theses and Dissertations--Medical Sciences

Blood-brain barrier disruption has been identified to associate with the pathogenesis several neurological diseases such as dementia [1, 2], multiple sclerosis[3, 4], acute or chronic cerebral ischemia[5], brain trauma[5], meningitis[5], encephalitis[5], stroke[6], and seizures[7]. Being able to effectively identify blood-brain barrier disruption is limited in methodology. The current standard is using a cerebrospinal fluid (CSF) albumin to serum albumin index, which requires the use of a lumbar puncture. A novel method of identifying blood-brain barrier disruption utilizing blood biomarkers is proposed in this study. Participants in this study had previously collected blood and CSF samples, which were analyzed to compare …

Copy Number Alterations Of Aggressive Pituitary Neuroendocrine Tumors, Grace Zhang

Scripps Senior Theses

Pituitary neuroendocrine tumors (PitNETs) are tumors of the pituitary gland. Although most are benign, they can cause severe morbidity if compression of surrounding tissue and/or endocrinopathies occur.

Aggressive PitNETs are notably detrimental and difficult to predict, and their effects are further exacerbated by challenges in treatment. Although histological studies can detect certain markers of tumor aggressiveness, they are insufficient at wholly predicting PitNET aggressiveness, making the clinical behavior of PitNETs challenging to determine. Since treatment of aggressive tumors also remains suboptimal, this further results in negative impacts on health and quality of life.

Genetic markers, such as copy number variations …

Sp1 Trans-Activates The Murine H+-K+-Atpase Α2-Subunit Gene, Xiaobo Wang, Yili Zhang, Xiuyun Zhou, Xiumei Xia, Weijun Teng, Lin Sheng, Jing Ding

Faculty, Staff and Student Publications

Acute lung injury (ALI) followed with severe inflammation and oxidative stress. Anti-inflammatory and antioxidant are the properties of aquaporin 1 (AQP1) and aquaporin 5 (AQP5). The goal of this study was to see if soy isoflavone can diminish lipopolysaccharide (LPS)-induced ALI and the underling mechanism. LPS-induced ALI was given to Sprague-Dawley rats 14 days following oophorectomy. One hour before the LPS challenge, estradiol (1 mg/kg) was administered subcutaneously as positive control and soy isoflavone was intragastric administration for 14 days prior to LPS challenge with different doses. Six hours after LPS challenge, the pulmonary edema, pathophysiology, inflammation, and the oxidative …

Incog 2.0 Guidelines For Cognitive Rehabilitation Following Traumatic Brain Injury, Part Iii: Executive Functions, Eliyas Jeffay, Jennie Ponsford, Amber Harnett, Shannon Janzen, Eleni Patsakos, Jacinta Douglas, Mary Kennedy, Ailene Kua, Robert Teasell, Penny Welch-West, Mark Theodore Bayley, Robin Green

Communication Sciences and Disorders Faculty Articles and Research

Introduction:

Moderate-to-severe traumatic brain injury (MS-TBI) causes debilitating and enduring impairments of executive functioning and self-awareness, which clinicians often find challenging to address. Here, we provide an update to the INCOG 2014 guidelines for the clinical management of these impairments.

Methods:

An expert panel of clinicians/researchers (known as INCOG) reviewed evidence published from 2014 and developed updated recommendations for the management of executive functioning and self-awareness post-MS-TBI, as well as a decision-making algorithm, and an audit tool for review of clinical practice.

Results:

A total of 8 recommendations are provided regarding executive functioning and self-awareness. Since INCOG 2014, 4 …

Dynamics And Mechanisms Of Erk Activation After Different Protocols That Induce Long-Term Synaptic Facilitation In Aplysia, Yili Zhang, Rong-Yu Liu, Paul Smolen, Leonard J Cleary, John H Byrne

Faculty, Staff and Student Publications

Phosphorylation of the MAPK family member extracellular signal–regulated kinase (ERK) is required to induce long-term synaptic plasticity, but little is known about its persistence. We examined ERK activation by three protocols that induce long-term synaptic facilitation (LTF) of the Aplysia sensorimotor synapse – the standard protocol (five 5-min pulses of 5-HT with interstimulus intervals (ISIs) of 20 min), the enhanced protocol (five pulses with irregular ISIs, which induces greater and longer-lasting LTF) and the two-pulse protocol (two pulses with ISI 45 min). Immunofluorescence revealed complex ERK activation. The standard and two-pulse protocols immediately increased active, phosphorylated ERK (pERK), which decayed …

Nasal Accumulation And Metabolism Of Δ9-Tetrahydrocannabinol Following Aerosol (‘Vaping’) Administration In An Adolescent Rat Model, Alexa Torrens, Christina M Ruiz, Maricela X Martinez, Alex Mabou Tagne, Pritam Roy, Dakota Grimes, Faizy Ahmed, Valeria Lallai, Victoria Inshishian, Malia Bautista, Yen-Chu Chen, Marilyn A. Huestis, Aditi Das, Christie D Fowler, Stephen V Mahler, Daniele Piomelli

Institute of Emerging Health Professions Faculty Papers

Passive aerosol exposure to Δ9-tetrahydrocannabinol (THC) in laboratory animals results in faster onset of action and less extensive liver metabolism compared to most other administration routes and might thus provide an ecologically relevant model of human cannabis inhalation. Previous studies have, however, overlooked the possibility that rodents, as obligate nose breathers, may accumulate aerosolized THC in the nasal cavity, from where the drug might directly diffuse to the brain. To test this, we administered THC (ten 5-s puffs of 100 mg/mL of THC) to adolescent (31-day-old) Sprague-Dawley rats of both sexes. We used liquid chromatography/tandem mass spectrometry to quantify the …

Visualization And Characterization Of The Immunological Synapse Between Chlorotoxin Chimeric Antigen (Cltx-Car) Redirected T Cells And Targeted Glioblastoma Tumors, Arianna Livi

CMC Senior Theses

Chimeric Antigen Receptor T (CAR-T) cells have demonstrated anti-tumor activity against aggressive and invasive cancers such as glioblastoma (GBM); however, clinical response rates remain low in clinical trial studies. Tumor heterogeneity and tumor microenvironment conditions pose significant challenges for treatment of GBM, thus continuous optimization of CAR-T cell therapies and identification of novel, widely expressed, and highly specific GBM antigens are vital to better patient outcomes. A newly developed CAR-T cell construct incorporating chlorotoxin (CLTX) as the targeting domain exhibited broad GBM-targeting capabilities and elicited potent cytotoxic effects during preclinical studies and is currently being tested in a phase I …

Incog 2.0 Guidelines For Cognitive Rehabilitation Following Traumatic Brain Injury, Part V: Memory, Diana Velikonja, Jennie Ponsford, Shannon Janzen, Amber Harnett, Eleni Patsakos, Mary Kennedy, Leanne Togher, Robert Teasell, Amanda Mcintyre, Penny Welch-West, Ailene Kua, Mark Theodore Bayley

Communication Sciences and Disorders Faculty Articles and Research

Introduction:

Memory impairments affecting encoding, acquisition, and retrieval of information after moderate-to-severe traumatic brain injury (TBI) have debilitating and enduring functional consequences. The interventional research reviewed primarily focused on mild to severe memory impairments in episodic and prospective memory. As memory is a common focus of cognitive rehabilitation, clinicians should understand and use the latest evidence. Therefore, the INCOG (“International Cognitive”) 2014 clinical practice guidelines were updated.

Methods:

An expert panel of clinicians/researchers reviewed evidence published since 2014 and developed updated recommendations for intervention for memory impairments post-TBI, a decision-making algorithm, and an audit tool for review of clinical practice. …

Incog 2.0 Guidelines For Cognitive Rehabilitation Following Traumatic Brain Injury: What’S Changed From 2014 To Now?, Mark Theodore Bayley, Shannon Janzen, Amber Harnett, Peter Bragge, Leanne Togher, Ailene Kua, Eleni Patsakos, Lyn S. Turkstra, Robert Teasell, Mary Kennedy, Shawn Marshall, Jennie Ponsford

Communication Sciences and Disorders Faculty Articles and Research

IT IS CRITICAL TO KEEP clinical practice guidelines (CPGs) up to date through integration of the latest evidence. Therefore, it is with great excitement that the INCOG team presents the INCOG 2.0 Guidelines for Cognitive Rehabilitation Following Traumatic Brain Injury (TBI). In this brief introduction, we provide an overview of changes in the evidence from 2014; share insights into the current state and challenges implementing cognitive rehabilitation; and provide an overview of INCOG 2022.

Support Their Sleep: Enhancing Nurses' Knowledge And Implementation Of Non-Pharmacological Sleep Protocols To Improve Patient Rest, Recovery, And Reduce Cognitive Impairment., David C. Barry

Master's Theses and Capstones

Background: Sleep and rest play an influential role in promoting recovery and healing in humans. Hospitalized patients are at risk for altered sleep from hospitalization, illness, and stimulation from a hospital environment. Non-pharmacologic interventions preformed by nurses can help to improve sleep and sleep environment for patients.

Local problem: There was no protocol or available information regarding patient sleep promotion for nurses to references when caring for patients.

Methods: Nurses in the microsystem (n=8) were administered a pre/post questionnaire containing Likert scales and a short quiz containing knowledge-based questions. Questionnaires were distributed to nurses prior to and after …

Syntaxin 3b Is A T-Snare Specific For Ribbon Synapses Of The Retina, Mariajose Perez-Hurtado, Calvin Dao, Amanda E Saenz, Ruth Heidelberger

Faculty, Staff and Student Publications

Biallelic loss-of-function mutations in the syntaxin 3 gene have been linked to a severe retinal dystrophy in humans that presents in early childhood. In mouse models, biallelic inactivation of the syntaxin 3 gene in photoreceptors rapidly leads to their death. What is not known is whether a monoallelic syntaxin 3 loss-of-function mutation might cause photoreceptor loss with advancing age. To address this question, we compared the outer nuclear layer of older adult mice (≈ 20 months of age) that were heterozygous for syntaxin 3 with those of similarly-aged control mice. We found that the photoreceptor layer maintains its thickness in …

Alterations In Static And Dynamic Regional Homogeneity In Mesial Temporal Lobe Epilepsy With And Without Initial Precipitating Injury, Xinyue Mao, Xiaonan Zhang, Chengru Song, Keran Ma, Kefan Wang, Xin Wang, Yajun Lian, Yong Zhang, Shaoqiang Han, Jingliang Cheng, Yan Zhang

Faculty, Staff and Student Publications

Objectives

Initial precipitating injury (IPI) such as febrile convulsion and intracranial infection will increase the susceptibility to epilepsy. It is still unknown if the functional deficits differ between mesial temporal lobe epilepsy with IPI (mTLE-IPI) and without IPI (mTLE-NO).

Methods

We recruited 25 mTLE-IPI patients, 35 mTLE-NO patients and 33 healthy controls (HC). Static regional homogeneity (sReHo) and dynamic regional homogeneity (dReHo) were then adopted to estimate the alterations of local neuronal activity. One-way analysis of variance was used to analyze the differences between the three groups in sReHo and dReHo. Then the results were utilized as masks for further …

Traumatic Brain Injury-Associated Epigenetic Changes And The Risk For Neurodegenerative Diseases, Paul Smolen, Pramod K Dash, John B Redell

Faculty, Staff and Student Publications

Epidemiological studies have shown that traumatic brain injury (TBI) increases the risk for developing neurodegenerative diseases (NDs). However, molecular mechanisms that underlie this risk are largely unidentified. TBI triggers widespread epigenetic modifications. Similarly, NDs such as Alzheimer's or Parkinson's are associated with numerous epigenetic changes. Although epigenetic changes can persist after TBI, it is unresolved if these modifications increase the risk of later ND development and/or dementia. We briefly review TBI-related epigenetic changes, and point out putative feedback loops that might contribute to long-term persistence of some modifications. We then focus on evidence suggesting persistent TBI-associated epigenetic changes may contribute …

More Management Is Needed To Improve The Effectiveness Of Artificial Grassland In Vegetation And Soil Restoration On The Three-River Headwaters Region Of China, Nengyu Wang, Jiayi Wan, Mingjun Ding, Hua Zhang, Shicheng Li, Linshan Liu, Yili Zhang

Faculty, Staff and Student Publications

Establishing an artificial grassland is a common measure employed to restore heavily degraded alpine grasslands for regional sustainability. The Three-River Headwaters Region in China has significant areas of black-soil-type grassland which is typified by heavy degradation; nearly 35% of the grassland regions in the Three-River Headwaters Region has degraded into this type. There are different plant community types of black-soil-type grasslands, however, it is not clear which restoration measures should be adopted for different kinds of black-soil-type grasslands. Here, we investigate the plant community characteristics and soil physicochemical properties of artificial grasslands, two types of black-soil-type grasslands, and native undegraded …

The Role Of The Nlrp3 Inflammasome In Alzheimer's Disease, Ethan S. Terman

Undergraduate Research Posters

This study examines the consequences of Alzheimer’s in rat and mice test subjects. The goal is to identify the effects of certain NLRP3 inhibiting drugs and to see if there are any noticeable effects in regards to impeding the pathological development of Alzheimer’s disease. The results are visualized by implementing the immunohistochemical process to identify neurodegeneration in the brain and to assess the expression levels of amyloid beta as an indicator of Alzheimer’s pathology. Other tests are also conducted on these transgenic mice to gauge cognitive functioning levels during the onset of their disease, those being behavior tests, but not …

Incog 2.0 Guidelines For Cognitive Rehabilitation Following Traumatic Brain Injury, Part Iv: Cognitive-Communication And Social Cognition Disorders, Leanne Togher, Jacinta Douglas, Lyn S. Turkstra, Penny Welch-West, Shannon Janzen, Amber Harnett, Mary Kennedy, Ailene Kua, Eleni Patsakos, Jennie Ponsford, Robert Teasell, Mark Theodore Bayley, Catherine Wiseman-Hakes

Communication Sciences and Disorders Faculty Articles and Research

Introduction:

Moderate to severe traumatic brain injury causes significant cognitive impairments, including impairments in social cognition, the ability to recognize others' emotions, and infer others' thoughts. These cognitive impairments can have profound negative effects on communication functions, resulting in a cognitive-communication disorder. Cognitive-communication disorders can significantly limit a person's ability to socialize, work, and study, and thus are critical targets for intervention. This article presents the updated INCOG 2.0 recommendations for management of cognitive-communication disorders. As social cognition is central to cognitive-communication disorders, this update includes interventions for social cognition.

Methods:

An expert panel of clinicians/researchers reviewed evidence published since …

The Future Of Incog (Is Now), Peter Bragge, Mark Theodore Bayley, Diana Velikonja, Leanne Togher, Jennie Ponsford, Shannon Janzen, Amber Harnett, Ailene Kua, Eleni Patsakos, Amanda Mcintyre, Robert Teasell, Mary Kennedy, Shawn Marshall

Communication Sciences and Disorders Faculty Articles and Research

IT HAS BEEN 8 years since the first iteration of the INCOG clinical practice guidelines (CPGs) were published. Much has happened since 2014, and a considerable body of evidence has been published in the various domains of cognitive rehabilitation research represented in this special issue. Over this time, significant developments in the science of identifying, appraising, and distilling research evidence into practically applicable CPGs have emerged, as well as implementation efforts to ensure meaningful change in care delivery.

Investigating The Effects Of Flotation Restricted Environment Stimulation Therapy On Neural Networks In Chronic Pain Patients Via Functional Magnetic Resonance Imaging And Other Modalities, Tyler Austin Mcgaughey

Graduate Theses, Dissertations, and Problem Reports (ETD)

Chronic lower back pain (CLBP) is one of the leading causes of disability worldwide, with an estimated direct cost of over 600 billion dollars in the US alone. CLBP profoundly impacts the patient, their support team, and the healthcare system. Widespread changes to the patient's well-being, including mental health, are seen in CLBP and contribute to a downward spiral that often leads to disability. Chronic pain is poorly understood and is difficult to treat because of its subjective nature. Recent improvements in pain assessment in the clinic and in biomedical research have had a profoundly impacted the field. More than …

P120-Catenin Subfamily Members Have Distinct As Well As Shared Effects On Dendrite Morphology During Neuron Development In Vitro, Maxsam S Donta, Yogesh Srivastava, Christina M Di Mauro, Adriana Paulucci-Holthauzen, M Neal Waxham, Pierre D Mccrea

Faculty, Staff and Student Publications

Dendritic arborization is essential for proper neuronal connectivity and function. Conversely, abnormal dendrite morphology is associated with several neurological pathologies like Alzheimer's disease and schizophrenia. Among major intrinsic mechanisms that determine the extent of the dendritic arbor is cytoskeletal remodeling. Here, we characterize and compare the impact of the four proteins involved in cytoskeletal remodeling-vertebrate members of the p120-catenin subfamily-on neuronal dendrite morphology. In relation to each of their own distributions, we find that p120-catenin and delta-catenin are expressed at relatively higher proportions in growth cones compared to ARVCF-catenin and p0071-catenin; ARVCF-catenin is expressed at relatively high proportions in the …