A5016118703- Spinal Cord Injury Research
- Glaucoma and retinal disorders
- Neurogenesis and neuroplasticity mechanisms
- Nerve injury and regeneration
- Retinal Development and Disorders
- RNA Interference and Gene Delivery
- Retinal Diseases and Treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Virus-based gene therapy research
- Glioma Diagnosis and Treatment
- Transcranial Magnetic Stimulation Studies
- Neuroscience and Neural Engineering
- Photoreceptor and optogenetics research
- Nerve Injury and Rehabilitation
- Traumatic Brain Injury and Neurovascular Disturbances
- Pluripotent Stem Cells Research
- Advanced biosensing and bioanalysis techniques
- Tissue Engineering and Regenerative Medicine
- Neuroscience and Neuropharmacology Research
- MicroRNA in disease regulation
- Mitochondrial Function and Pathology
- Traumatic Brain Injury Research
- Neurological Disorders and Treatments
- Intracerebral and Subarachnoid Hemorrhage Research
- Calpain Protease Function and Regulation
Houston Methodist
2016-2025
Cornell University
2003-2024
University of Washington
2008-2023
Lancashire Care NHS Foundation Trust
2021
Neurological Surgery
2008-2020
California Institute for Regenerative Medicine
2015-2016
Center for Neuro-Oncology
2008-2015
Seattle University
2010-2014
University of Washington Medical Center
2009
Harborview Medical Center
2005
The existence of multipotent progenitor populations in the adult forebrain has been widely studied. To extend this knowledge to spinal cord we have examined proliferation, distribution, and phenotypic fate dividing cells rat cord. Bromodeoxyuridine (BrdU) was used label 13- 14-week-old, intact Fischer rats. Single daily injections BrdU were administered over a 12 d period. Animals killed either 1 or 4 weeks after last injection BrdU. We observed frequent cell division throughout rodent cord,...
Glaucoma is characterized by retinal ganglion cell (RGC) pathology and a progressive loss of vision. Previous studies suggest RGC death responsible for vision in glaucoma, yet evidence from other neurodegenerative diseases suggests axonal degeneration, the absence neuronal loss, can significantly affect function. To characterize degeneration DBA/2 mouse model we quantified RGCs mice various ages using neuronal-specific nuclear protein (NeuN) immunolabeling, retrograde labeling, optic nerve...
An early hallmark of neuronal degeneration is distal transport loss and axon pathology. Glaucoma involves the retinal ganglion cell (RGC) neurons their axons in optic nerve. Here we show that, like other neurodegenerations, injury appears mouse glaucoma. Where RGC terminate superior colliculus, reduction active follows a retinotopic pattern resembling glaucomatous vision loss. Like glaucoma, susceptibility to deficits increases with age not necessarily associated elevated ocular pressure....
Little is known about molecular changes occurring within retinal ganglion cells (RGCs) before their death in glaucoma. Taking advantage of the fact that γ-synuclein (Sncg) mRNA expressed specifically and highly adult mouse RGCs, we show DBA/2J model glaucoma there not only a loss expressing this gene, but also downregulation gene expression Sncg many other genes large numbers RGCs. This RGCs occurs together with reductions FluoroGold (FG) retrograde transport. Surprisingly, are...
Abstract Background Tumor cell invasion into adjacent normal brain is a mesenchymal feature of GBM and major factor contributing to their dismal outcomes. Therefore, better understandings mechanisms that promote change in are great clinical importance address invasion. We previously showed the bHLH transcription TWIST1 which orchestrates carcinoma metastasis through an epithelial transition (EMT) upregulated promotes SF767 line vitro . Results To further define functions we tested impact...
Intraocular pressure (IOP) elevation is a principal risk factor for glaucoma. Using microbead injection technique to chronically raise IOP 15 or 30 d in mice, we identified the early changes visual response properties of different types retinal ganglion cells (RGCs) and correlated these with neuronal morphology before cell death. Microbead-injected eyes showed reduced optokinetic tracking as well In such eyes, multielectrode array recordings revealed that four RGC show diverse alterations...
Abstract The adult mammalian spinal cord contains neural stem and/or progenitor cells that slowly multiply throughout life and differentiate exclusively into glia. contribution of progenitors to repair has been highlighted in recent studies, demonstrating extensive cell proliferation gliogenesis following central nervous system (CNS) trauma. present experiments aimed determine the relative roles endogenously dividing versus quiescent posttraumatic gliogenesis. Using mitotic indicator...
The DBA/2J mouse is a model for secondary angle-closure glaucoma, due to iris atrophy and pigment dispersion, which ultimately lead increased intraocular pressure (IOP). study was undertaken correlate changes in retinal gene expression with IOP elevation by performing microarray analysis of RNA from mice at 3 months before disease onset 8 after elevation.IOP monitored monthly animals, animals normal (3 months) or elevated (8 were identified. prepared three individual retinas each age, the...
Abstract In many CNS diseases, proliferation becomes dysregulated; cells divide and participate in pathological processes. Gliosis is a fundamental response to trauma or disease which cell hypertrophy play prominent roles. The DBA/2J mouse glaucoma model mice experience gliosis concomitant with raised intraocular pressure that leads slow progressive retinal ganglion axonopathy. We sought determine if glaucomatous changes DBA/2 retina would alter the regulation of proliferation, specifically...
We tested the hypothesis that glaucoma disrupts electrophysiological conduction properties and axon function in optic nerve as a of intraocular pressure (IOP) levels age DBA/2J mouse model glaucoma. The amplitude integral electrical signals evoked along axons decreased considerably by 6 months increasing IOP levels. At young ages, raised was directly associated with increased vulnerability to metabolic challenge. Changes physiological nerves were accentuated aging, leading loss compound...
Glaucoma is a neurodegenerative disease that results in the progressive decline and ultimate death of retinal ganglion cells (RGCs). While multiple risk factors are associated with glaucoma, mechanisms leading to onset progression remain unknown. Molecular analysis various glaucoma models has revealed involvement non-neuronal cell populations, including astrocytes, Mueller glia microglia, at early stages glaucoma. High-dose irradiation was reported have significant long-term protective...
Oxidative stress has been implicated in neurodegenerative diseases, including glaucoma. However, due to the lack of clinically relevant models and expense long-term testing, few studies have modeled antioxidant therapy for prevention neurodegeneration. We investigated contribution oxidative pathogenesis glaucoma DBA/2J mouse model Similar other we observed lipid peroxidation upregulation stress-related mRNA protein retina. To test role disease progression, chose deliver naturally occurring,...
Decreased ATP correlates with intraocular pressure exposure in the optic nerves of mice glaucoma. To understand what underlies this energy deficit, we examined mitochondria myelinated nerve axons DBA/2J mouse, a model glaucoma secondary to iris pigment disease, and DBA/2(wt-gpnmb) control strain.Mitochondrial length, width, surface area, health status were measured 30 electron microscopic fields within portion from at 3, 6, 10 months age. Protein was isolated for analysis PINK1, Parkin,...
To determine the importance of NMDA receptor (NMDAR) in pain hypersensitivity after injury, NMDAR1 (NR1) subunit was selectively deleted lumbar spinal cord adult mice by localized injection an adenoassociated virus expressing Cre recombinase into floxed NR1 mice. mRNA and dendritic protein are reduced 80% area injection, currents, but not AMPA 86–88% lamina II neurons. The spatial knock-out does alter heat or cold paw-withdrawal latencies, mechanical threshold, motor function. However,...
The pattern of remyelination after traumatic spinal cord injury remains elusive, with animal and human studies reporting partial to complete demyelination followed by incomplete remyelination. In the present study, we found that spared rubrospinal tract (RST) axons passage traced actively transported dextrans examined caudally lesion 12 weeks mouse contusion were fully remyelinated. Spared exhibited a marginally reduced myelin thickness significantly shorter internodes. CASPR...
To investigate quantitatively the relationships between elevated intraocular pressure (IOP), axonal loss, and corneal thickness in DBA/2 mouse model of glaucoma, to understand better how these factors contribute disease progression.IOP was measured with a handheld tonometer (Tono-Pen; Medtronic Solan, Jacksonville, FL) 195 446 eyes mice 2 10 months age sampled from colony 400 mice. From group 24 at 4, 9, age, correlations were determined density number RGC axons, thickness, IOP.Mean IOP...
Progenitors that express NG2-proteoglycan are the predominant self-renewing cells within CNS. NG2 progenitors replenish oligodendrocyte populations intact stem cell niche, and cycling among first to react CNS insults. We investigated role of after spinal cord injury how bone morphogen protein signals remodel progressive postinjury (PI) niche. Progeny labeled by an NG2-specific reporter virus undergo a coordinated shift in differentiation profile. progeny born 24 h PI produce scar-forming...
Neurological diseases and trauma often cause demyelination, resulting in the disruption of axonal function integrity. Endogenous remyelination promotes recovery, but process is not well understood because no method exists to definitively distinguish regenerated from preexisting myelin. To date, remyelinated segments have been defined as anything abnormally short thin, without empirical data corroborate these morphological assumptions. identify myelin, we used a transgenic mouse with an...
Many ophthalmologists and members of the lay public alike view glaucoma in its historical context—that is, as exclusively a disease eye. This has been (and remains) overwhelmingly pervasive because etiology involves so many factors associated with eye: intraocular pressure (IOP), corneal thickness, optic disc morphology, on. Glaucoma is sensitivity to IOP, lowering IOP through either topical application hypotensive drugs or surgery only form treatment. Studies animal models generally...
Aging is associated with many functional and morphological central nervous system changes. It important to distinguish between changes created by normal aging those caused disease. In the present study we characterized myelin within murine rubrospinal tract found that internode lengths significantly decrease as a function of age which suggests active remyelination. We also analyzed proliferation, distribution phenotypic fate dividing cells Bromodeoxyuridine (5-bromo-2-deoxyuridine, BrdU)....