A5018868816- Traumatic Brain Injury and Neurovascular Disturbances
- Cytokine Signaling Pathways and Interactions
- Spine and Intervertebral Disc Pathology
- TGF-β signaling in diseases
- Neuroinflammation and Neurodegeneration Mechanisms
- Signaling Pathways in Disease
- Renin-Angiotensin System Studies
- S100 Proteins and Annexins
- Immune Cell Function and Interaction
- Neuropeptides and Animal Physiology
- Proteoglycans and glycosaminoglycans research
- Reproductive System and Pregnancy
- Nerve injury and regeneration
- Immune Response and Inflammation
- Peptidase Inhibition and Analysis
- Musculoskeletal pain and rehabilitation
- Connective tissue disorders research
- Traumatic Brain Injury Research
- Mitochondrial Function and Pathology
- Congenital heart defects research
- Spinal Cord Injury Research
- Ion channel regulation and function
- Neurogenesis and neuroplasticity mechanisms
- Effects of Radiation Exposure
- Protein Tyrosine Phosphatases
Uniformed Services University of the Health Sciences
2015-2025
Center for Neuroscience and Regenerative Medicine
2012-2015
Regenerative Medicine Institute
2015
University of Health Science
2010
Columbia University
2005
Columbia University Irving Medical Center
2004
Massachusetts General Hospital
1992-1998
Harvard University
1993-1998
Regeneron (United States)
1998
Laboratory of Molecular Genetics
1994
Glycosaminoglycan (GAG) side chains endow extracellular matrix proteoglycans with diversity and complexity based upon the length, composition charge distribution of polysaccharide chain. Using cultured primary neurons, we show that specific sulfation in GAG chondroitin sulfate mediates neuronal guidance cues axonal growth inhibition. Chondroitin-4-sulfate (CS-A), but not chondroitin-6-sulfate (CS-C), exhibits a strong negative cue to mouse cerebellar granule neurons. Enzymatic gene-based...
See Moon (doi:10.1093/awv239) for a scientific commentary on this article. Traumatic brain injury frequently leads to long-term cognitive problems and physical disability yet remains without effective therapeutics. results in neuronal death, acute prolonged inflammation decreased blood flow. Drugs that block angiotensin II type 1 receptors (AT1R, encoded by AGTR1) (ARBs or sartans) are strongly neuroprotective, neurorestorative anti-inflammatory. To test whether these drugs may be treating...
Traumatic brain injury (TBI) results in a loss of tissue at the moment impact cerebral cortex. Subsequent secondary involves release molecular signals with dramatic consequences for integrity damaged tissue, leading to evolution pericontusional-damaged area minutes days after initial injury. The mechanisms behind progression remain under investigation. In this study, we analyzed spatial-temporal profile blood flow, apoptotic, and astrocytic-vascular events cortical regions around site time...
TBI (traumatic brain injury) triggers an inflammatory cascade, gliosis and cell proliferation following death in the pericontusional area surrounding site of injury. In order to better understand proliferative response CCI (controlled cortical impact) injury, we systematically analyzed phenotype dividing cells at several time points post-lesion. C57BL/6 mice were subjected mild moderate over left sensory motor cortex. At different injected with BrdU (bromodeoxyuridine) four times 3-h...
Leptin is an adipocyte-derived cytokine that regulates food intake and body weight via interaction with its Ob receptor (ObR). Serum leptin levels are chronically elevated in obese humans, suggesting obesity may be associated resistance the inability to generate adequate ObR response. Evidence suggests transcriptional activation of target genes by STAT3 (signal transducer activator transcription) hypothalamus a critical pathway mediates leptin's action. Herein we report induces tyrosine...
Chondroitin sulfate proteoglycans (CSPGs) play a pivotal role in many neuronal growth mechanisms including axon guidance and the modulation of repair processes following injury to spinal cord or brain. Many actions CSPGs central nervous system (CNS) are governed by specific sulfation pattern on glycosaminoglycan (GAG) chains attached CSPG core proteins. To elucidate sulfated GAG traumatic brain (TBI), controlled cortical impact mild moderate severity was performed over left sensory motor...
Commercially available angiotensin II AT2 receptor antibodies are widely employed for localization and quantification, but they have not been adequately validated. In this study, we characterized three commercially antibodies: 2818-1 from Epitomics, sc-9040 Santa Cruz Biotechnology, Inc., AAR-012 Alomone Labs. Using western blot analysis the immunostaining patterns observed were different every antibody tested, in most cases consisted of multiple immunoreactive bands. Identical present...
The receptor for leukemia inhibitory factor (LIFR), in combination with the signal-transducing subunit interleukin-6-type cytokine receptors, gp130, and LIF, activates transcription of acute-phase plasma protein genes human rat hepatoma cells vasoactive intestinal peptide gene a neuroblastoma cell line. To identify regions within cytoplasmic domain LIFR that initiate signal transduction independently we constructed chimeric by linking extracellular granulocyte colony-stimulating (G-CSFR) to...
Traumatic injury to the CNS results in increased expression and deposition of chondroitin sulfate proteoglycans (CSPGs) that are inhibitory axonal regeneration. Transforming growth factor-β (TGF-β) has been implicated as a major mediator these changes, but mechanisms through which TGF-β regulates CSPG not known. Using lentiviral expressed Smad-specific ShRNA we show induction astrocytes is Smad-dependent. However, find differential dependence synthetic machinery on Smad2 and/or Smad3....
Traumatic brain injury (TBI) increases neurogenesis in the forebrain subventricular zone (SVZ) and hippocampal dentate gyrus (DG). Transforming growth factor-β (TGF-β) superfamily cytokines are important regulators of adult neurogenesis, but their involvement regulation this process after is unclear. We subjected mice to controlled cortical impact (CCI) injury, isolated RNA from SVZ DG at different post-injury time points. qPCR array analysis showed that caused significant alterations mRNA...
Ciliary neurotrophic factor (CNTF) and leukemia inhibitory (LIF) are members of a family neuropoietic cytokines that have broad range actions on many different neuronal populations. In cultured sympathetic neurons, CNTF LIF induce transcription the VIP other neuropeptide genes as part program differentiation. To gain insight into nuclear events involved in cytokine-mediated activation differentiation, we investigated mechanisms transcriptional vasoactive intestinal peptide (VIP) gene by...
Journal Article Structure and methylation of the human calcitonin/α-CGRP gene Get access P.M. Broad, Broad Search for other works by this author on: Oxford Academic PubMed Google Scholar A.J. Symes, Symes R.V. Thakker, Thakker 1Department Medicine, University College Middlesex School MedicineThe Hospital, Mortimer Street, London W1P 7PN, UK Present address: + Division Molecular Clinical Research Centre, Watford Road, Harrow, HA1 3UJ R.K. Craig * § Department Biotechnology, I, 10...
To investigate transforming growth factor beta (TGFbeta) regulation of connective tissue (CTGF) expression in cells the nucleus pulposus rats, mice, and humans.Real-time reverse transcription-polymerase chain reaction Western blot analyses were used to measure CTGF pulposus. Transfections effects Smads 2, 3, 7 activator protein 1 (AP-1) on TGFbeta-mediated promoter activity.CTGF was lower neonatal rat discs than skeletally mature discs. An increase activity observed after TGFbeta treatment....
Traumatic Brain injury-induced disturbances in mitochondrial fission-and-fusion dynamics have been linked to the onset and propagation of neuroinflammation neurodegeneration. However, cell-type-specific contributions crosstalk between neurons, microglia, astrocytes mitochondria-driven neurodegeneration after brain injury remain undefined. We developed a human three-dimensional vitro triculture tissue model contusion composed examined dysregulation progression Pharmacological studies...
Abstract: The neurotransmitter phenotype switch that occurs in cultures of rat superior cervical ganglion neurons after treatment with leukemia inhibitory factor or ciliary neurotrophic is a useful model permitting investigation the mechanisms cytokine‐mediated differentiation. Recently actions and have been linked through their interactions related receptor complexes. Here we compare effects these two cytokines on gene expression sympathetic neuronal begin to investigate mechanisms. We...
Targeting the endocannabinoid system has emerged as an effective strategy for treatment of inflammatory and neurological diseases. Unlike inhibition principal 2-arachidonyl glycerol (2-AG) hydrolytic enzyme monoacylglycerol lipase (MAGL), which leads to 2-AG overload cannabinoid receptor desensitization, selective minor alpha, beta-hydrolase domain 6 (ABHD6) can provide therapeutic benefits without producing cannabimimetic side effects. We have shown that ABHD6 significantly reduces...
Angiotensin II (Ang II)-mediated activation of its type I receptor (AT1R) in the central nervous system promotes glial proliferation, local inflammation, and a decrease cerebral blood flow. Angiotensin-(1-7) (Ang-(1-7))-an Ang derivative peptide-signals through Mas (MasR) opposition to II/AT1R, promoting anti-inflammatory, vasodilatory, neuroprotective effects. As our laboratory has previously demonstrated beneficial effects AT1R inhibition following controlled cortical impact (CCI) mice, we...
Affective disorders including depression (characterized by reduced motivation, social withdrawal, and anhedonia), anxiety, irritability are frequently reported as long-term consequences of mild traumatic brain injury (mTBI) in addition to cognitive deficits, suggesting a possible dysregulation within mood/motivational neural circuits. One the important regions that control motivation mood is lateral habenula (LHb), whose hyperactivity associated with depression. Here, we used repetitive...