A5090536089- Traumatic Brain Injury and Neurovascular Disturbances
- Traumatic Brain Injury Research
- S100 Proteins and Annexins
- Neuroscience and Neuropharmacology Research
- Alzheimer's disease research and treatments
- Mitochondrial Function and Pathology
- Neuroinflammation and Neurodegeneration Mechanisms
- Anesthesia and Neurotoxicity Research
- Tryptophan and brain disorders
- Memory and Neural Mechanisms
- Peroxisome Proliferator-Activated Receptors
- Stress Responses and Cortisol
- Migraine and Headache Studies
- Neurogenesis and neuroplasticity mechanisms
- Neurological Disease Mechanisms and Treatments
- Inflammatory mediators and NSAID effects
- Calcium signaling and nucleotide metabolism
- Ion channel regulation and function
- Sirtuins and Resveratrol in Medicine
- Neurological Disorders and Treatments
- Cancer-related cognitive impairment studies
- Cancer Mechanisms and Therapy
- Genomics and Phylogenetic Studies
- Cancer-related molecular mechanisms research
- Genetic and Kidney Cyst Diseases
Case Western Reserve University
2018-2025
University of Puerto Rico at Río Piedras
2011-2025
University School
2023-2024
Louis Stokes Cleveland VA Medical Center
2018-2024
University Hospitals of Cleveland
2020-2024
University Hospitals Cleveland Medical Center
2018-2024
Geriatric Research Education and Clinical Center
2018-2023
Discovery Institute
2022
University of Iowa
2015-2018
Significance Chronic neurodegeneration, a major cause of the long-term disabilities that afflict survivors traumatic brain injury (TBI), is linked to an increased risk for late-life neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s vascular dementia, and chronic encephalopathy. Here, we report on restoration blood–brain barrier (BBB) structure function by P7C3-A20 when administered 12 mo after TBI. This pharmacotherapy was associated with cessation neurodegeneration...
Abstract Background Tau is aberrantly acetylated in various neurodegenerative conditions, including Alzheimer’s disease, frontotemporal lobar degeneration (FTLD), and traumatic brain injury (TBI). Previously, we reported that reducing tau by pharmacologically inhibiting p300-mediated acetylation at lysine 174 reduces pathology improves cognitive function animal models. Methods We investigated the therapeutic efficacy of two different antibodies specifically target on (ac-tauK174). treated...
Compounds targeting the sigma 2 receptor, which we recently cloned and showed to be identical with transmembrane protein 97 (σ2R/TMEM97), are broadly applicable therapeutic agents currently in clinical trials for imaging breast cancer treatment of Alzheimer's disease schizophrenia. These promising applications coupled our previous observation that σ2R/TMEM97 modulator SAS-0132 has neuroprotective attributes improves cognition wild-type mice suggests modulating may also have benefits other...
There are currently no therapeutic options for patients with Parkinson's disease that prevent or slow the death of dopaminergic neurons. We have recently identified novel P7C3 class neuroprotective molecules blocks neuron cell death.The aim this study was to determine whether treatment highly active members series and associated behavioral neurochemical deficits in rat 6-hydroxydopamine (6-OHDA) model disease.After unilateral injection 6-OHDA into median forebrain bundle, rats were assessed...
Abstract There is a critical need for translating basic science discoveries into new therapeutics patients suffering from difficult to treat neuropsychiatric and neurodegenerative conditions. Previously, target-agnostic in vivo screen mice identified P7C3 aminopropyl carbazole as capable of enhancing the net magnitude postnatal neurogenesis by protecting young neurons death. Subsequently, neuroprotective efficacy compounds broad spectrum preclinical rodent models has also been observed. An...
Oxidative damage in the brain is one of earliest drivers pathology Alzheimer’s disease (AD) and related dementias, both preceding exacerbating clinical symptoms. In response to oxidative stress, nuclear factor erythroid 2-related 2 (Nrf2) normally activated protect from damage. However, Nrf2-mediated defense against stress declines AD, rendering increasingly vulnerable Although this phenomenon has long been recognized, its mechanistic basis a mystery. Here, we demonstrate through vitro vivo...
Progression of acute traumatic brain injury (TBI) into chronic neurodegeneration is a major health problem with no protective treatments. Here, we report that acutely elevated mitochondrial fission after TBI in mice triggers persisting 17 months later, equivalent to many human decades. We show increased mouse related levels 1 protein (Fis1) and Fis1 also TBI. Pharmacologically preventing from binding its partner, dynamin-related (Drp1), for 2 weeks normalizes the balance fission/fusion...
Supramolecular hacky sacks (SHS) are a novel class of self-assembled colloidal particles formed from guanosine (G) derivatives, designed to function as versatile tools for cellular and therapeutic applications. Here, we investigate the structure-dependent uptake, intracellular trafficking, functional performance SHS particles. Confocal microscopy flow cytometry studies reveal that uptake is highly dependent on composition G-derivatives, suggesting selective interactions with pathways....
Highly effective modulator therapies (HEMT) are increasing the lifespan for many people with cystic fibrosis (pwCF), making it necessary to identify and understand CF specific age-related consequences. In this study, we examine impact of aging on cognitive function brain pathology in a mouse model focusing phospho-Tau (pTau) pathology. Cognitive was measured by novel object recognition spontaneous alternation behavior tests. Hippocampal neuronal assessed measuring long-term potentiation...
Approximately 30–50% of the >30 million HIV-infected subjects develop neurological complications ranging from mild symptoms to dementia. HIV does not infect neurons, and molecular mechanisms behind HIV-associated neurocognitive decline are understood. There several hypotheses explain development dementia in HIV+ individuals, including neuroinflammation mediated by infected microglia neuronal toxicity proteins. A key protein associated with HIV, gp120, forms part viral envelope can be found...
Chronic complications of traumatic brain injury represent one the greatest financial burdens and sources suffering in society today. A substantial number these patients suffer from posttraumatic headache (PTH), which is typically associated with tactile allodynia. Unfortunately, this phenomenon has been understudied, large part because lack well-characterized laboratory animal models. We have addressed gap field by characterizing sensory profile 2 nonpenetrating models PTH. show that...
The polyunsaturated fatty acid (PUFA) synthases from deep-sea bacteria invariably contain multiple acyl carrier protein (ACP) domains in tandem. This conserved tandem arrangement has been implicated both amplification of production (additive effect) and structural stabilization the multidomain (synergistic effect). While more accepted model is one which act independently, recent reports suggest that ACP may form higher oligomers. Elucidating three-dimensional structure arrangements therefore...
EFhd2 is a calcium binding protein, which highly expressed in the central nervous system and associated with pathological forms of tau proteins tauopathies. Previous phosphoproteomics studies bioinformatics analysis suggest that may be phosphorylated. Here, we determine whether Cdk5, hyperactivated kinase tauopathies, phosphorylates influence its known molecular activities. The results indicated phosphorylated by brain extract transgenic mouse CK-p25, overexpresses Cdk5 constitutive...
Traumatic brain injury (TBI)-induced axonal degeneration leads to acute and chronic neuropsychiatric impairment, neuronal death, accelerated neurodegenerative diseases of aging, including Alzheimer's Parkinson's diseases. In laboratory models, is traditionally studied through comprehensive postmortem histological evaluation integrity at multiple time points. This requires large numbers animals power for statistical significance. Here, we developed a method longitudinally monitor functional...
Abstract Background Emerging evidence links Alzheimer’s disease (AD) to dysfunction of the primary cilium, a historically overlooked organelle that serves as neuron’s antenna. All neurons harbor single cilium projects from membrane sense changes in extracellular environment. Primary cilia leads group diseases called ‘ciliopathies’, which are associated with reduced hippocampal and cortical mass, well neurocognitive impairment. Ciliopathies place individuals at higher risk for dementia,...
Aims: Impaired embryonic cortical interneuron development from prenatal stress is linked to adult neuropsychiatric impairment, stemming in part excessive generation of reactive oxygen species the developing embryo. Unfortunately, there are no preventive medicines that mitigate risk embryo, as underlying pathophysiologic mechanisms poorly understood. Our goal was interrogate molecular basis stress-mediated damage brain identify a neuroprotective strategy. Results: Chronic mice dysregulated...
Ca2+-binding protein 1 (CaBP1) is a Ca2+-sensing similar to calmodulin that potently regulates voltage-gated Ca2+ channels. Unlike calmodulin, however, CaBP1 mainly expressed in neuronal cell-types and enriched the hippocampus, where its function unknown. Here, we investigated role of hippocampal-dependent behaviors using mice lacking expression (C-KO). By western blot, largest splice variant, caldendrin, was detected hippocampal lysates from wild-type (WT) but not C-KO mice. Compared WT...
The jet-flow overpressure chamber (OPC) has been previously reported as a model of blast-mediated traumatic brain injury (bTBI). However, rigorous characterization the features this apparatus shows that it fails to recapitulate exposure an isolated blast wave. Through combined experimental and computational modeling analysis gas-dynamic flow conditions, we show here OPC produces collimated high-speed jet with extreme dynamic pressure delivers severe compressive impulse. Variable rupture...
Traumatic brain injury (TBI) afflicts 70 million people worldwide annually and is the 3rd overall risk factor for developing Alzheimer's disease (AD), behind genetics aging. In patients with AD, a history of TBI associated 3-4 year earlier onset cognitive impairment. AD share many pathologies, including blood barrier dysfunction, neuroinflammation, protein aggregation. Yet, underlying mechanism this relationship not understood, there are no treatments that protect from accelerated after TBI....
As we get older, various aspects of our bodies start to decline, including brain function. The mechanisms behind the decline in function due aging are still not well understood. blood-brain barrier (BBB) is crucial for maintaining health and homeostasis by controlling both passive active exchange materials between blood brain. This predominantly composed endothelial cells, which deteriorate neurodegenerative disorders. Endothelial cells also highly enriched Kruppel-like factor 4 (KLF4)...