A5069304796- Neuroscience of respiration and sleep
- Neonatal and fetal brain pathology
- Neuroendocrine regulation and behavior
- Neonatal Respiratory Health Research
- Infant Health and Development
- Sleep and Wakefulness Research
- Advanced Neuroimaging Techniques and Applications
- Restraint-Related Deaths
- Infant Development and Preterm Care
- Traumatic Brain Injury and Neurovascular Disturbances
- Prenatal Substance Exposure Effects
- Nicotinic Acetylcholine Receptors Study
- Heart Rate Variability and Autonomic Control
- Neuroscience and Neuropharmacology Research
- Cannabis and Cannabinoid Research
- Genetics and Neurodevelopmental Disorders
- Neurogenesis and neuroplasticity mechanisms
- Traumatic Brain Injury Research
- Grief, Bereavement, and Mental Health
- Preterm Birth and Chorioamnionitis
- Neurotransmitter Receptor Influence on Behavior
- Fetal and Pediatric Neurological Disorders
- Metabolism and Genetic Disorders
- Autism Spectrum Disorder Research
- Smoking Behavior and Cessation
Boston Children's Hospital
2016-2025
Harvard University
2015-2025
Marquette University
2023
St. Catherine University
2022
Lemuel Shattuck Hospital
2017
Phoenix Children's Hospital
2016
Brigham and Women's Hospital
2004-2016
National Health Laboratory Service
2016
University of South Dakota
2003-2016
Sanford Research
2010-2016
Hypoxic-ischemic injury to the periventricular cerebral white matter [periventricular leukomalacia (PVL)] results in palsy and is leading cause of brain premature infants. The principal feature PVL a chronic disturbance myelination suggests that oligodendrocyte (OL) lineage progression disrupted by ischemic injury. We determined OL stages at risk for during developmental window vulnerability (23-32 weeks, postconceptional age). In 26 normal control autopsy human brains, was defined parietal...
The timing and synchronization of postnatal myelination in the human central nervous system (CNS) are complex. We found eight time-related patterns CNS during first two years autopsied infants. intensity was graded 162 infants with diverse diseases on an ordinal scale degrees 0-4. Ayer method for maximum likelihood estimates censored data utilized to generate curves temporal changes percent 0 through 4 myelin 62 white matter sites. These sites fall into subgroups determined by presence or...
This study establishes the sequence of myelination in a population autopsied infants from birth through second postnatal year. Myelination was assessed 62 precisely defined central nervous system (CNS) sites 162 with diverse diseases who were 1972 to 1984 at Children's Hospital, Boston. The degree graded on an ordinal scale 0-4 using inferior cerebellar peduncle as internal standard. grading is modification that used for fetal National Collaborative Perinatal Project (NCPP). data are...
Neuropathologic studies in SIDS victims support the concept that they are not entirely 'normal' prior to death, but rather possess underlying vulnerabilities which put them at risk for sudden death. This forms a key link triple-risk model pathogenesis of proposed by us. According this model, death results from intersection three overlapping factors: (1) vulnerable infant; (2) critical developmental period homeostatic control, and (3) an exogenous stressor(s). An infant will die only if...
ContextThe serotonergic (5-hydroxytryptamine [5-HT]) neurons in the medulla oblongata project extensively to autonomic and respiratory nuclei brainstem spinal cord help regulate homeostatic function. Previously, abnormalities 5-HT receptor binding medullae of infants dying from sudden infant death syndrome (SIDS) were identified, suggesting that medullary dysfunction may be responsible for a subset SIDS cases.ObjectiveTo investigate cellular defects associated with altered pathways...
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...
The ascending reticular activating system (ARAS) mediates arousal, an essential component of human consciousness. Lesions the ARAS cause coma, most severe disorder Because current methodological limitations, including postmortem tissue analysis, neuroanatomic connectivity is poorly understood. We applied advanced imaging technique high angular resolution diffusion (HARDI) to elucidate structural in 3 adult brains, 2 which were imaged postmortem. High tractography identified previously...
Neuroimaging studies indicate reduced volumes of certain gray matter regions in survivors prematurity with periventricular leukomalacia (PVL). We hypothesized that subacute and/or chronic lesions are increased incidence and severity PVL cases compared to non-PVL at autopsy. Forty-one premature infants were divided based on cerebral white histology: (n = 17) gliosis focal necrosis; diffuse (DWMG) without "Negative" group 7) no abnormalities. Neuronal loss was found almost exclusively PVL,...
Muscarinic cholinergic activity in the human arcuate nucleus at ventral medullary surface is postulated to be involved cardiopulmonary control. A significant decrease [ 3 H]quinuclidinyl benzilate binding muscarinic receptors now shown occur sudden infant death syndrome (SIDS) infants, compared infants dying acutely of known causes. In with chronic oxygenation abnormalities, low other nuclei, as well nucleus. The deficit SIDS might contribute a failure responses challenges during sleep.
The sudden infant death syndrome (SIDS) is postulated to result from a failure of homeostatic responses life-threatening challenges (e.g. asphyxia, hypercapnia) during sleep. ventral medulla participates in sleep-related responses, including chemoreception, arousal, airway reflex control, thermoregulation, respiratory drive, and blood pressure regulation, part via serotonin its receptors. humans contains the arcuate nucleus, which we have shown isolated defects muscarinic kainate receptor...
Abstract The cellular basis of myelin deficits detected by neuroimaging in long‐term survivors periventricular leukomalacia (PVL) is poorly understood. We tested the hypothesis that oligodendrocyte lineage (OL) cell density reduced PVL, thereby contributing to subsequent deficits. Using computer‐based methods, we determined OL sections from 18 PVL and age‐adjusted control cases, immunostained with OL‐lineage marker Olig2. Myelination was assessed basic protein (MBP) immunostaining. found no...
Abstract After completion of neuronal migration to form the cerebral cortex, axons undergo rapid elongation their intra‐ and subcortical targets, from midgestation through infancy. We define axonal development in human parietal white matter this critical period. Immunocytochemistry Western blot analysis were performed on 46 normative cases 20–183 postconceptional (PC) weeks. Anti‐SMI 312, a pan‐marker neurofilaments, stained as early 23 32, marker for nonphosphorylated neurofilament high...
Immature oligodendrocytes (OLs) derive from a large pool of late OL progenitors that populate human cerebral white matter throughout the latter half gestation. We recently reported minor population immature OLs are present in for at least 3 months before these cells commit to myelinogenesis around 30 wk postconceptional age. Since this finding supports dissociation between events regulate maturation and their commitment myelinogenesis, we characterized here cellular sequence characterize...
The rate of the sudden infant death syndrome (SIDS) among American Indian infants in Northern Plains is almost 6 times higher than U.S. white infants. In a study mortality Indians, we tested hypothesis that receptor binding abnormalities to neurotransmitter serotonin (5-HT) SIDS cases, compared with autopsied controls, occur regions medulla oblongata contain 5-HT neurons and are critical for regulation cardiorespiration central chemosensitivity during sleep, i.e. medullary system....
Although microglial activation may be an initial beneficial response to a variety of insults, prolonged can release toxic substances and lead cell death. Microglial secondary hypoxia-ischemia and/or infection in immature cerebral white matter is important the pathogenesis periventricular leukomalacia (PVL), major pathological substrate palsy premature infant. We hypothesize that transient overexpression activated density occurs normally human fetus during peak window vulnerability for PVL....
To test the hypothesis that profile of sudden infant death syndrome (SIDS) changed after Back-to-Sleep (BTS) campaign initiation, document prevalence and patterns multiple risks, determine age risk factors.The San Diego SIDS/Sudden Unexplained Death in Childhood Research Project recorded factors for 568 SIDS deaths from 1991 to 2008 based upon standardized scene investigations autopsies. Risks were divided into intrinsic (eg, male gender) extrinsic prone sleep).Between 1991-1993 1996-2008,...
A current hypothesis that the sudden infant death syndrome (SIDS) is a sleep apnea precipitated by defective control of involuntary respiration prompted present study in which "reactive gliosis" sections medulla oblongata 45 SIDS victims was quantitated and compared with 20 infants. Six anatomic regions were studied; five are related one unrelated to neural respiration. Increased numbers "reactive" astrocytes found group when counts for all combined (P = .04). Counts also significantly...