Nervous System Diseases Commons^™

The Neuroprotective Role Of Lipoxin A4 In Reinstating Blood Brain Barrier Integrity In Neuroinflammatory Disease Processes, Minjal Patel, Nimish Acharya

Rowan-Virtua Research Day

Background: The blood-brain barrier (BBB), formed by the vascular endothelium, astrocytic foot processes, pericytes, is a highly selective barrier that is responsible for maintaining brain homeostasis and ultimately proper neuronal function. Disruption of the BBB, leading to increased BBB permeability, has been reported in several neurodegenerative diseases, including Alzheimer’s disease (AD) and traumatic brain injury (TBI).¹ Loss of BBB integrity leads to the proliferation of pro-inflammatory cytokines, including TNFɑ, IL-1β, and IL-6.² Moderate inflammation has a beneficial response in the system following an acute injury. However, prolonged inflammation has been known to perturb homeostasis and have …

Pediatric Neurotropic Infection Alters Synaptic Development In The Developing Brain, Anuoluwapo Grace Fadare, Yashika S. Kamte, Manish N. Chandwani, Lauren A. O'Donnell

Rowan-Virtua Research Day

Many neurotropic viruses cause more significant pathology in younger hosts as their brains are still developing. This experiment asked how central nervous system (CNS) viral-infections affect the development of synapses in the pediatric brain during infection and post-infection. Synaptogenesis is at its peak in pediatric mice (10 days old) and we hypothesized that a neurotropic infection could disrupt synaptic proteins. We used a transgenic mouse model where measles virus (MV) infects only mature neurons, leading us to question whether synapses were impacted. We examined synaptic markers in the cerebellum and hippocampus in MV-infected and uninfected mice 9 days and 90 …

A Preliminary Report On The Role Of Lipoxin A4 In Reinstating The Blood-Brain Barrier Integrity In A Rodent Model Of Acute Inflammation With Impaired Cerebrovasculature, Minjal Patel, Shruti Varshney, Ananya Nethikunta, George G. Godsey, Mary C. Kosciuk, Ana Rodriguez, Bernd Spur, Kingsley Yin, Randel L. Swanson, Venkat Venkataraman, Robert G. Nagele, Nimish Acharya

Rowan-Virtua Research Day

Background: The blood-brain barrier (BBB) is responsible for maintaining brain homeostasis and ultimately proper neuronal function. Disruption of the BBB, leading to increased BBB permeability, has been reported in several neurodegenerative diseases, including Alzheimer’s disease (AD) and traumatic brain injury (TBI). Lipoxins (LXs) are a class of arachidonate-derived eicosanoids, which are a class of specialized pro-resolving lipid mediators (SPMs). SPMs are known to inhibit immune response through inhibition of cellular infiltration, downregulation of pro-inflammatory mediators and upregulation of anti-inflammatory mediators. Hence, LXs are recognized as “breaking signals” in the inflammatory process. One form of LXs, Lipoxin A4 (LXA4) …

Emerging Unconventional Therapies For Glioblastoma Multiforme, Danielle Morang

Capstone Showcase

Glioblastoma multiforme (GBM) is the most prevalent and aggressive primary malignant brain tumor occurring in adults with a median survival of less than two years. It is a highly invasive tumor characterized by genetic heterogeneity, angiogenesis, and rapid proliferation. Patients undergo a multimodal treatment regimen consisting of surgical resection and chemoradiation therapy, yet GBM tumors almost always recur with a worsening prognosis. The molecular and genetic complexities of GBM pose a significant challenge for developing effective therapeutics. Thus, it is imperative to identify new therapeutic targets and explore novel treatment strategies to improve patients’ overall survival time and quality of …

Extravasated Brain-Reactive Autoantibodies Perturb Neuronal Surface Protein Expression In Alzheimer's Pathology, Wardah Bajwa, Mary Kosciuk, Randel L. Swanson, Anuradha Krishnan, Venkat Venkataraman, Robert Nagele, Nimish Acharya

Rowan-Virtua Research Day

Background: Increased blood-brain barrier (BBB) permeability is reported in both the neuropathological and in vivo studies in both Alzheimer’s Disease (AD) and age matched cognitively normal, no cognitive impairment (NCI), subjects. Impaired BBB allows various vascular components such as immunoglobulin G (IgG) to extravasate into the brain and specifically bind to various neuronal surface proteins (NSP), also known as brain reactive autoantibodies (BrABs). This interaction is predicted to further enhance deposition of amyloid plaques.

Hypothesis: Interaction between extravasated BrABs and its cognate NSPs lower the expression of that NSPs in AD patients.

Methods: We selected Western blotting technique to study …

Differential Degeneration Of Neurons In A Mouse Model Of Canavan Disease, Vibha Chauhan, Quy Nguyen, Jeremy Francis, Paola Leone

Rowan-Virtua Research Day

Canavan disease (CD) is an inherited leukodystrophy caused by inactivating mutations to the glial enzyme aspartoacylase (ASPA). ASPA catabolizes neuronal N-acetylaspartate (NAA) into free acetate and aspartate and loss of this function results in the chronic elevation of non-catabolized NAA and the failure of developmental myelination. Elevated NAA is thought to cause damage to myelin and myelin-producing cells (oligodendrocytes, but the viability of neurons in CD is relatively unexplored. We compare here the progressive degeneration of neurons in two regions of the CD mouse brain, the thalamus and the cortex, distinguished by differing degrees of vacuolation, and show that the …

Mclena-1: A Phase Ii Clinical Trial For The Assessment Of Safety, Tolerability, And Efficacy Of Lenalidomide In Patients With Mild Cognitive Impairment Due To Alzheimer's Disease; Trial Design And Rationale, Boris Decourt

Annual Research Symposium

No abstract provided.

The Brodmann Area 39/40 Of The Brain In Alzheimer’S, Mild Cognitive Impairment, And No Cognitive Impairment Subjects At Advanced Age Demonstrate Comparable Levels Of Blood-Brain Barrier Breach, Dhara Rana, Forum Mangrola, Randel L. Swanson, Venkat Venkataraman, David A. Bennett, Zoe Arvanitakis, David Libon, Robert Nagele, Nimish Acharya

Rowan-Virtua Research Day

• Alzheimer’s disease (AD) is one of the most common form of dementia

• Mild cognitive impairment (MCI), specifically amnestic subtype, more likely to progress to AD

• Pathogenesis Theories:

• o Accumulation of amyloid-beta peptides and neurofibrillary tangles containing hyperphosphorylated neuronal tau protein
• o Blood Brain Barrier (BBB) dysfunction is associated with AD pathogenesis

• Brodmann area 39/40: regions of parietal cortex are responsible for language, spatial cognition, memory retrieval, attention, phonological processing, and emotional processing

• Hypothesis: An increased BBB permeability in Brodmann area 39/40 of AD and age-matched MCI and no cognitive impairment (NCI) subjects

Plasmalogen Deficiency: A Risk Factor For Dementias And Potential Treatment Target, Mitchel A. Kling, Mallika Mendu, Rima F. Kaddurah-Daouk, Sheldon Jordan, Dayan B. Goodenowe

Rowan-Virtua Research Day

Altered lipid metabolism is implicated in the risk of sporadic Alzheimer’s disease (AD) and related dementias (ADRD); however, the precise mechanisms accounting for findings from observational studies remains to be fully elucidated.

Plasmalogens are a subclass of integral membrane phospholipids with unique properties that appear to play important roles relevant to the pathophysiology of AD and ADRD, including vesicle fusion necessary for synaptic neurotransmitter release, modulation of membrane fluidity and microdomain dynamics, membrane antioxidant functions, and neuroprotection. Like the more familiar phosphatides, plasmalogens are synthesized on a 3-carbon glycerol backbone; however, they differ from phosphatides by the presence of a …

Characterizing The Heterogeneity Of Adult-Onset Leukoencephalopathy With Axonal Spheroids: A Digital Spatial Profiling Study, Peter Liu

Undergraduate Student Research Internships Conference

Adult-onset leukoencephalopathy with axonal spheroids (ALAS) is a group of hereditary, progressive, neurodegenerative disorders involving primarily the central nervous system white matter (WM). ALAS is characterized by patchy, asymmetrical myelin loss and axonal destruction in the WM, predominantly involving the frontoparietal regions. However, the asymmetrical and heterogenous involvement of different brain regions remains poorly characterized.

In this study, digital spatial profiling was performed to investigate the region-specific expressions of 60 proteins. Conventional immunohistochemistry methods was used validate intrepretation of probes. Using a high-plex and high-throughput method, we provide evidence of regional heterogeneity in ALAS, particularly involving key markers of microglia …

The Scripps Research Institute Summer Undergraduate Research Fellowship, Ezana Assefa

Trick to the Treat of Internships and Research

This program is a 10-week internship designed for undergraduates interested in the scientific field to engage in current research. Students have the option of requesting to work under three mentors, one of which they will be paired. Students will work in the lab with the principal investigator and other members of the lab. Along with working in the lab, students in the program will also attend bi-weekly talks/lectures from researchers, grad students, and professionals at TSRI as well as participating in two presentations and a final poster or oral presentation.