A5091795035- Neurogenesis and neuroplasticity mechanisms
- MicroRNA in disease regulation
- Neuroinflammation and Neurodegeneration Mechanisms
- Multiple Sclerosis Research Studies
- Extracellular vesicles in disease
- Nerve injury and regeneration
- Mitochondrial Function and Pathology
- Neural dynamics and brain function
- Mesenchymal stem cell research
- Histone Deacetylase Inhibitors Research
- Immune cells in cancer
- Neuroscience and Neuropharmacology Research
- Peroxisome Proliferator-Activated Receptors
- Neurological disorders and treatments
- Neuropeptides and Animal Physiology
- Parkinson's Disease Mechanisms and Treatments
- Nanocluster Synthesis and Applications
- HER2/EGFR in Cancer Research
- Reproductive System and Pregnancy
- Multiple Myeloma Research and Treatments
- Barrier Structure and Function Studies
- Traumatic Ocular and Foreign Body Injuries
- HIV-related health complications and treatments
- Nitric Oxide and Endothelin Effects
- Immune Response and Inflammation
Washington University in St. Louis
2025
George Washington University
2015-2024
Gifu Women's University
2020
University of Pittsburgh
2013-2015
University Hospitals of Cleveland
2011
Case Western Reserve University
2011
Oligodendrocytes, the myelin-forming cells of CNS, exquisitely tailor thickness individual myelin sheaths to diameter their target axons maximize speed action potential propagation, thus ensuring proper neuronal connectivity and function. Following demyelinating injuries adult newly formed oligodendrocytes frequently generate new sheaths. episodes demyelination such as those that occur in patients with multiple sclerosis, however, matching axon fails leaving remyelinated thin potentially...
Development of pharmacotherapies that promote remyelination is a high priority for multiple sclerosis (MS), due to their potential neuroprotection and restoration function through repair demyelinated lesions. A novel preparation clean-surfaced, faceted gold nanocrystals demonstrated robust remyelinating activity in response demyelinating agents both chronic cuprizone acute lysolecithin rodent animal models. Furthermore, oral delivery improved motor functions cuprizone-treated mice open field...
Astrocytes have been implicated in regulating oligodendrocyte development and myelination vitro, although their functions vivo remain less well defined. Using a novel approach to locally ablate GFAP+ astrocytes, we demonstrate that astrocytes are required for normal CNS myelin compaction during development, maintaining integrity the adult. Transient ablation of mouse spinal cord first postnatal week reduced numbers mature oligodendrocytes inhibited formation, while prolonged resulted lacked...
Synapses are involved in the communication of information from one neuron to another. However, a systematic analysis synapse density neocortex diversity species is lacking, limiting what can be understood about evolution this fundamental aspect brain structure. To address this, we quantified supragranular layers II-III and infragranular V-VI primary visual cortex inferior temporal sample 25 primates, including humans. We found that densities were relatively constant across these levels...
Successful myelin repair in the adult CNS requires robust and timely production of proteins to generate new sheaths. The underlying regulatory mechanisms complex molecular basis regeneration, however, remain poorly understood. Here, we investigate role ERK MAP kinase signaling this process. Conditional deletion Erk2 from cells oligodendrocyte lineage resulted delayed remyelination following demyelinating injury mouse corpus callosum. occurred as a result specific deficit translation major...
Multiple sclerosis (MS) is a chronic, immune-mediated, demyelinating disease of the central nervous system (CNS). There no known cure for MS, and currently available drugs managing this are only effective early on have many adverse side effects. Results from recent studies suggest that histone deacetylase (HDAC) inhibitors may be useful treatment autoimmune inflammatory diseases such as MS. However, underlying mechanisms by which HDACs influence immune-mediated MS unclear. More importantly,...
During mammalian development, myelin-forming oligodendrocytes are generated and axons ensheathed according to a tightly regulated sequence of events. Excess premyelinating eliminated by apoptosis the timing onset myelination in any specific CNS region is highly reproducible. Although developing recovers more effectively than adult from similar insults, it unknown whether early loss oligodendrocyte lineage cells leads long-term functional deficits. To directly assess during postnatal spinal...
Abstract HIV-associated neurocognitive disorders (HAND) are a spectrum of cognitive impairments that continue to affect approximately half all HIV-positive individuals despite effective viral suppression through antiretroviral therapy (ART). White matter pathologies have persisted in the ART era, and degree white damage correlates with impairment patients HAND. The HIV protein Nef has been implicated HAND pathogenesis, but its effect on not well characterized. Here, utilizing vivo, ex vitro...
Abstract Multiple sclerosis (MS) is a central nervous system (CNS) autoimmune disease characterized by inflammation, demyelination, and neurodegeneration. The ideal MS therapy would both specifically inhibit the underlying response promote repair/regeneration of myelin as well maintenance axonal integrity. Currently approved therapies consist non‐specific immunosuppressive molecules/antibodies which block activation or CNS homing autoreactive T cells, but there are no for stimulation...
Multiple sclerosis (MS) is characterized by a compromised blood-brain barrier (BBB) resulting in central nervous system (CNS) entry of peripheral lymphocytes, including T cells and B cells. While have largely been considered the main contributors to neuroinflammation MS, success cell depletion therapies suggests an important role for MS pathology. Glial CNS are essential components both disease progression recovery, raising possibility that they represent targets functions. Here, we examine...
Bone marrow mesenchymal stem cells (BM-MSCs) are an attractive cell based therapy in the treatment of CNS demyelinating diseases such as multiple sclerosis (MS). Preclinical studies demonstrate that BM-MSCs can effectively reduce clinical burden and enhance recovery experimental autoimmune encephalomyelitis (EAE), a commonly used animal model MS. However, number recent trials have not shown significant functional benefit following BM-MSC infusion into MS patients. One possibility for...
Insults to the central nervous system (CNS) elicit common glial responses including microglial activation evidenced by functional, morphological, and phenotypic changes, as well astrocyte reactions hypertrophy, altered process orientation, changes in gene expression function. However, cellular molecular mechanisms that initiate modulate such response are less well-defined. Here we show an adult cortical lesion generates a population of ultrastructurally unique microglial-like cells express...
ABSTRACT The cerebral cortex accounts for substantial energy expenditure, primarily driven by the metabolic demands of synaptic signaling. Mitochondria, organelles responsible generating cellular energy, play a crucial role in this process. We investigated ultrastructural characteristics primary visual 18 phylogenetically diverse mammals, spanning broad range brain sizes from mouse to elephant. Our findings reveal remarkable uniformity synapse density, postsynaptic density (PSD) length, and...
Multiple sclerosis (MS) is a CNS neurodegenerative autoimmune disease characterized by loss of oligodendrocytes and myelin in the brain spinal cord that results localized functional deficits. Several risk factors have been associated with MS, however none fully explain enhanced susceptibility seen older individuals. Epidemiological data, based on geographical prevalence studies suggest established early life frequently long before diagnosis raising possibility developmental events influence...
Abstract Disease, injury, and aging induce reactive astrocyte states with pathological functions 1-4 . In neurodegenerative diseases, inflammatory astrocytes are abundant contribute to progressive cell loss. Modulating the state or function of these thereby represents an attractive therapeutic goal 5,6 Leveraging a cellular phenotypic screening platform, we show that chemical inhibitors HDAC3 effectively block reactivity. Inhibition reduces molecular functional features in vitro including...
Abstract Development of pharmacotherapies that promote remyelination are a high priority for multiple sclerosis (MS) due to their potential neuroprotection and restoration function through repair demyelinated lesions. A novel preparation clean-surfaced, faceted gold nanocrystals demonstrated robust remyelinating activity in response demyelinating agents both chronic cuprizone acute lysolecithin rodent animal models. Furthermore, oral delivery improved motor functions cuprizone-treated mice...