A5040759848- Neuroscience and Neuropharmacology Research
- Endodontics and Root Canal Treatments
- Ion channel regulation and function
- Neuroinflammation and Neurodegeneration Mechanisms
- Neonatal and fetal brain pathology
- Dental Radiography and Imaging
- Dental Anxiety and Anesthesia Techniques
- Adenosine and Purinergic Signaling
- Neurogenesis and neuroplasticity mechanisms
- Trace Elements in Health
- Mitochondrial Function and Pathology
- Epilepsy research and treatment
- Dental Trauma and Treatments
- Neonatal Respiratory Health Research
- Neuroscience and Neural Engineering
- Nitric Oxide and Endothelin Effects
- Anesthesia and Neurotoxicity Research
- Dental materials and restorations
- Genetic Neurodegenerative Diseases
- Neuroscience of respiration and sleep
- Molecular Sensors and Ion Detection
- Periodontal Regeneration and Treatments
- Oral and Maxillofacial Pathology
- Sleep and Wakefulness Research
- Immune Response and Inflammation
Boston Children's Hospital
2016-2025
Harvard University
2014-2024
Boston Children's Museum
2022
New York University
2006-2020
Boston University
2020
Johns Hopkins University
2017
Johns Hopkins Bayview Medical Center
2017
American Association of Endodontists
1999-2015
Klinik Rosenberg
2007
McLean Hospital
2006
Innate immunity is an evolutionarily ancient system that provides organisms with immediately available defense mechanisms through recognition of pathogen-associated molecular patterns. We show in the CNS, specific activation innate a Toll-like receptor 4 (TLR4)-dependent pathway leads to neurodegeneration. identify microglia as major lipopolysaccharide (LPS)-responsive cell CNS. TLR4 extensive neuronal death vitro depends on presence microglia. LPS dramatic loss cultures prepared from...
Ferrostatin-1 (Fer-1) inhibits ferroptosis, a form of regulated, oxidative, nonapoptotic cell death. We found that Fer-1 inhibited death in cellular models Huntington's disease (HD), periventricular leukomalacia (PVL), and kidney dysfunction; lipid peroxidation, but not mitochondrial reactive oxygen species formation or lysosomal membrane permeability. developed mechanistic model to explain the activity Fer-1, which guided development ferrostatins with improved properties. These studies...
The immediate or innate immune response is the first line of defense against diverse microbial pathogens and requires expression recently discovered toll-like receptors (TLRs). TLR4 serves as a specific receptor for lipopolysaccharide (LPS) localized on surface subset mammalian cells. Although immunity necessary host pathogens, consequences its activation in CNS can be deleterious, we show here developing neural model. We examined major non-neuronal cell types found that microglia expressed...
Death of oligodendrocyte (OL) precursors can be triggered in vitro by cystine deprivation, a form oxidative stress that involves depletion intracellular glutathione. We report here OLs demonstrate maturation-dependent differences survival when subjected to free radical-mediated injury induced glutathione depletion. Using immunopanning isolate rat preoligodendrocytes (preOLs), we generated highly enriched populations preOLs and mature under chemically defined conditions. Cystine deprivation...
Periventricular white matter injury, the principal variety of brain injury human premature infant, involves differentiating oligodendroglia. Nothing is known biochemical mechanism oligodendroglial death in this disorder. Because an early event periventricular ischemia-induced axonal disruption and because such destruction could lead to a marked increase local concentrations glutamate, we evaluated vulnerability oligodendroglia glutamate culture model. Oligodendroglia were isolated from...
Periventricular leukomalacia (PVL), the major substrate of cerebral palsy in survivors prematurity, is defined as focal periventricular necrosis and diffuse gliosis immature white matter. We propose that nitrosative and/or oxidative stress to premyelinating oligodendrocytes complicating ischemia sick premature infant a key mechanism injury interfering with maturation these cells myelin-producing subsequent myelination. Using immunocytochemical markers autopsy brain tissue from 17 PVL cases...
Abstract Connections of the perirhinal cortex in the.rat brain were studied using anterograde ( 3 H‐proline/leucine) and retrograde (horseradish peroxidase) tracers. The receives major projections from medial precen‐tral, anterior cingulate, prelimbic, ventral lateral orbital, posterior agranular insular, temporal, superior granular parietal, occipital, retrosplenial, ectorhinal cortices, pre‐subiculum, subiculum, diagonal band Broca. Rostral neocortical areas project predominantly to...
Chen MY‐H, K‐L, C‐A, Tayebaty F, Rosenberg PA, Lin LM. Responses of immature permanent teeth with infected necrotic pulp tissue and apical periodontitis/abscess to revascularization procedures. International Endodontic Journal , 45 294–305, 2012. Abstract Aim To report several types response either periodontitis or abscess Methodology Twenty abscesses from 20 patients were included. The isolated rubber dam, chambers was accessed through the crowns. canals gently irrigated 5.25% sodium...
Reactive microglia in the CNS have been implicated pathogenesis of white matter disorders, such as periventricular leukomalacia and multiple sclerosis. However, mechanism by which activated kill oligodendrocytes (OLs) remains elusive. Here we show that lipopolysaccharide (LPS)-induced death developing OLs is caused microglia-derived peroxynitrite, reaction product nitric oxide (NO) superoxide anion. Blocking peroxynitrite formation with synthase inhibitors, dismutase mimics, or a...
GLT-1 (EAAT2; slc1a2) is the major glutamate transporter in brain, and predominantly expressed astrocytes, but at lower levels also excitatory terminals. We generated a conditional knock-out mouse to uncover cell-type-specific functional roles of GLT-1. Inactivation gene was achieved either neurons or astrocytes by expression synapsin-Cre inducible human GFAP-CreERT2. Elimination from resulted loss ∼80% protein uptake activity that could be solubilized reconstituted liposomes. This...
The excitatory neurotransmitter glutamate is released from axons and glia under hypoxic/ischemic conditions. In vitro , oligodendrocytes (OLs) express non-NMDA receptors (GluRs) are susceptible to GluR-mediated excitotoxicity. We evaluated the role of OL excitotoxicity in white matter injury developing brain. Hypoxic/ischemic thought mediate periventricular leukomalacia, an age-dependent lesion seen preterm infants a common antecedent cerebral palsy. Hypoxia/ischemia rat pups at postnatal...
Periventricular leukomalacia is a form of hypoxic-ischemic cerebral white matter injury seen most commonly in premature infants and the major antecedent palsy. Glutamate receptor-mediated excitotoxicity predominant mechanism to developing matter. We have demonstrated previously protective effect AMPA-kainate-type glutamate receptor blockade rodent model periventricular leukomalacia. The present study explores therapeutic potential for injury. demonstrate that AMPA receptors are expressed on...
Oxidative mechanisms of injury are important in many neurological disorders, including hypoxic-ischemic brain damage. Cerebral palsy after preterm birth is hypothesized to be caused by developing oligodendrocytes (OLs). Here we examined the developmental sensitivity OLs exogenous hydrogen peroxide (H 2 O ) with stage-specific rat oligodendrocyte cultures. We found that H itself or generated glucose oxidase was more toxic than mature OLs. Mature were able degrade faster OLs, suggesting higher...
GLT1 is the major glutamate transporter of brain and has been thought to be expressed exclusively in astrocytes. Although excitatory axon terminals take up glutamate, responsible not identified. at least two forms varying C termini, GLT1a GLT1b. mRNA demonstrated neurons, without associated protein. Recently, evidence presented, using specific terminus-directed antibodies, that GLT1b protein neurons vivo. These data suggested detected encodes also might elusive presynaptic transporter. To...
The pharmacological properties of glutamate agonists were compared in astrocyte-rich and astrocyte-poor cultures derived from embryonic rat cerebral cortex. object this investigation was to determine the extent which uptake might influence receptor-mediated neurotoxic actions these compounds. In cultures, using 30 min exposures, we observed that potencies poorly transported NMDA (35 microM) D-glutamate (89 higher than L-glutamate (205 microM). much more potent, with an EC50 5 +/- 4 microM...
Oxidative stress is believed to be the cause of cell death in multiple disorders brain, including perinatal hypoxia/ischemia. Glutamate, cystine deprivation, homocysteic acid, and glutathione synthesis inhibitor buthionine sulfoximine all oxidative injury immature neurons oligodendrocytes by depleting intracellular glutathione. Although vitamin K not a classical antioxidant, we report here novel finding that 1 2 (menaquinone-4) potently inhibit depletion-mediated primary cultures...
Identification of endogenous toxins and characterization the mechanisms by which produce cell injury death may help understand both normal modeling populations connections in CNS as well abnormal loss. The toxicity catecholamines intrinsic to was investigated using model system rat cerebral cortex dissociated culture. All tested, including norepinephrine (NE), dopamine, epinephrine, were toxic neurons glia at a concentration 25 microM when added cultures 24 hr after plating. Toxicity evident...
To identify glutamate transporters expressed in forebrain neurons, we prepared a cDNA library from rat neuronal cultures, previously shown to transport with high affinity and capacity. Using this library, cloned two forms, varying the C terminus, of transporter GLT1. This was found be localized exclusively astrocytes normal mature brain. Specific antibodies against C-terminal peptides were used show that neurons culture express both GLT1a GLT1b proteins. The pharmacological properties...