A5048837963- Neuroinflammation and Neurodegeneration Mechanisms
- Alzheimer's disease research and treatments
- Traumatic Brain Injury and Neurovascular Disturbances
- Neurogenesis and neuroplasticity mechanisms
- Anesthesia and Neurotoxicity Research
- Neurological Disease Mechanisms and Treatments
- Traumatic Brain Injury Research
- Tryptophan and brain disorders
- Neuroscience and Neuropharmacology Research
- Sleep and Wakefulness Research
- S100 Proteins and Annexins
- Memory and Neural Mechanisms
- Immune cells in cancer
- Computational Drug Discovery Methods
- Melanoma and MAPK Pathways
- Immune Response and Inflammation
- Circadian rhythm and melatonin
- MicroRNA in disease regulation
- Cardiac Arrest and Resuscitation
- Sleep and related disorders
- Adenosine and Purinergic Signaling
- Dementia and Cognitive Impairment Research
- GDF15 and Related Biomarkers
- Neuroscience of respiration and sleep
- Neonatal and fetal brain pathology
University of Kentucky
2016-2025
Spinal Injuries Center
2023
Cancer Research And Biostatistics
2019
University of South Florida
2006-2011
Florida College
2007-2009
Northwestern University
2009
The protective/neurotoxic role of fractalkine (CX3CL1) and its receptor CX3C chemokine 1 (CX3CR1) signaling in neurodegenerative disease is an intricate highly debated research topic it becoming even more complicated as new studies reveal discordant results. It appears that the CX3CL1/CX3CR1 axis plays a direct neurodegeneration and/or neuroprotection depending on CNS insult. However, all above focused pathological conditions, ignoring relevance under physiological conditions. No approach to...
Astrocytes are the most abundant cell type in brain and play a critical role maintaining healthy nervous tissue. In Alzheimer's disease (AD) other neurodegenerative disorders, many astrocytes convert to chronically "activated" phenotype characterized by morphologic biochemical changes that appear compromise protective properties and/or promote harmful neuroinflammatory processes. Activated emerge early course of AD become increasingly prominent as clinical pathological symptoms progress, but...
Abstract Background Overproduction of proinflammatory cytokines from activated microglia has been implicated as an important contributor to pathophysiology progression in both acute and chronic neurodegenerative diseases. Therefore, it is critical elucidate intracellular signaling pathways that are significant contributors cytokine overproduction exposed specific stressors, especially amenable drug interventions. The serine/threonine protein kinase p38α MAPK a key enzyme the parallel...
Neuropathological, genetic, and biochemical studies have provided support for the hypothesis that microglia participate in Alzheimer's disease (AD) pathogenesis. Despite extensive characterization of AD microglia, there are still many unanswered questions, little is known about microglial morphology other common forms age-related dementia: particularly, dementia with Lewy bodies (DLB) hippocampal sclerosis aging (HS-Aging). In addition, no prior attempted to compare contrast hippocampus...
Loss of physiological microglial function may increase the propagation neurodegenerative diseases. Cellular senescence is a hallmark aging; thus, we hypothesized age could be cause dystrophic microglia. Stereological counts were performed for total microglia, 2 microglia morphologies (hypertrophic and dystrophic) across human lifespan. An age-associated in number was found hippocampus frontal cortex. However, proportional to age-related Thus, aging alone does not explain presence We next...
Abstract Background Parkinson's disease is characterized by a progressive loss of dopaminergic neurons in the substantia nigra. The cause neurodegeneration unknown. Neuroinflammation has been clearly shown and may be involved nature disease. Microglia are capable producing neuronal damage through production bioactive molecules such as cytokines, well reactive oxygen species (ROS), nitric oxide (NO). inflammatory response brain tightly regulated at multiple levels. One form immune regulation...
We have studied the influence of predator stress (30 min cat exposure) on long-term (24 h) spatial memory and density spines in basilar dendrites CA1 neurons. Predator occurred either immediately before water maze training (Stress Pre-Training) or 24 h test Pre-Retrieval). The Control (nonstress) group exhibited excellent a robust increase stubby, but not mushroom, shaped spines. Stress Pre-Training had impaired did exhibit any changes spine density. Pre-Retrieval was also performance, this...
BackgroundNeurodevelopmental disorders are associated with altered patterns of neuronal connectivity. A critical determinant connectivity is the dendritic morphology individual neurons, which shaped by experience. The identification environmental exposures that interfere growth and plasticity may, therefore, provide insight into risk factors for neurodevelopmental disorders.ObjectiveWe tested hypothesis polychlorinated biphenyls (PCBs) alter and/or promoting activity ryanodine receptors...
Despite the extensive mechanistic and pathological characterization of amyloid precursor protein (APP)/presenilin-1 (PS-1) knock-in mouse model Alzheimer's disease (AD), very little is known about AD-relevant behavioral deficits in this model. Characterization baseline performance a variety functional tasks identification temporal onset impairments are important to provide foundation for future preclinical testing AD therapeutics. Here we perform comprehensive model, discuss how observed...
Neuropathology after traumatic brain injury (TBI) is the result of both immediate impact and secondary mechanisms. Unresolved post-traumatic glial activation a mechanism that contributes to chronic state neuroinflammation in animal models TBI human head patients. We recently demonstrated, using vitro models, p38α MAPK signaling microglia key event promoting cytokine production response diverse disease-relevant stressors subsequent inflammatory neuronal dysfunction. From these findings, we...
Neuroinflammation is an important secondary mechanism that a key mediator of the long-term consequences neuronal injury occur in traumatic brain (TBI). Microglia are highly plastic cells with dual roles and recovery. Recent studies suggest chemokine fractalkine (CX3CL1, FKN) mediates neural/microglial interactions via its sole receptor CX3CR1. CX3CL1/CX3CR1 signaling modulates microglia activation, depending upon type time injury, either protects or exacerbates neurological diseases.In this...
Risk factors and cognitive sequelae of brain arteriolosclerosis pathology are not fully understood. To address this, we used multimodal data from the National Alzheimer's Coordinating Center Disease Neuroimaging Initiative sets. Previous studies showed evidence distinct neurodegenerative disease outcomes clinical-pathological correlations in “oldest-old” compared to younger cohorts. Therefore, using set, analyzed clinical neuropathological two groups according ages at death: < 80 years (...
Clinically, perturbations in the semaphorin signaling system have been associated with autism and epilepsy. The semaphorins implicated guidance, migration, differentiation, synaptic plasticity of neurons. 3F (Sema3F) ligand its receptor, neuropilin 2 (NPN2) are highly expressed within limbic areas. NPN2 may intimately direct apposition presynaptic postsynaptic locations, facilitating development maturity hippocampal function. To further understand role central nevous (CNS) plasticity,...
Overproduction of proinflammatory cytokines in the CNS has been implicated as a key contributor to pathophysiology progression Alzheimer9s disease (AD), and extensive studies with animal models have shown that selective suppression excessive glial can improve neurologic outcomes. The prior art, therefore, raises logical postulation intervention drugs targeting dysregulated cytokine production might be effective disease-modifying therapeutics if used appropriate biological time window. To...
The first kinase inhibitor drug approval in 2001 initiated a remarkable decade of tyrosine drugs for oncology indications, but void exists serine/threonine protein and central nervous system indications. Stress kinases are special interest neurological neuropsychiatric disorders due to their involvement synaptic dysfunction complex disease susceptibility. Clinical preclinical evidence implicates the stress related p38αMAPK as potential neurotherapeutic target, isoform selective candidates...
Abstract Background The p38α MAPK isoform is a well-established therapeutic target in peripheral inflammatory diseases, but the importance of this kinase pathological microglial activation and detrimental inflammation CNS disorders less well understood. To test role microglia-dependent neuron damage, we used primary microglia from wild-type (WT) or conditional knockout (KO) mice co-culture with WT cortical neurons, measured damage after LPS insult. Results We found that neurons...