A5058695201- Neonatal and fetal brain pathology
- Neuroscience of respiration and sleep
- Neonatal Respiratory Health Research
- Neuroendocrine regulation and behavior
- Infant Health and Development
- Advanced Neuroimaging Techniques and Applications
- Infant Development and Preterm Care
- Preterm Birth and Chorioamnionitis
- Traumatic Brain Injury and Neurovascular Disturbances
- Sleep and Wakefulness Research
- Prenatal Substance Exposure Effects
- Genetics and Neurodevelopmental Disorders
- Functional Brain Connectivity Studies
- Cannabis and Cannabinoid Research
- Restraint-Related Deaths
- Antioxidant Activity and Oxidative Stress
- Mitochondrial Function and Pathology
- Neuroinflammation and Neurodegeneration Mechanisms
- Smoking Behavior and Cessation
- Genomics, phytochemicals, and oxidative stress
- Immune Response and Inflammation
- Anesthesia and Neurotoxicity Research
- Diet and metabolism studies
- Neurogenesis and neuroplasticity mechanisms
- Fungal Biology and Applications
Boston Children's Hospital
2016-2025
Boston Children's Museum
2005-2025
Harvard University
2014-2024
University of Leeds
2020
Barrow Neurological Institute
2016
Phoenix Children's Hospital
2016
Stellenbosch University
2016
National Health Laboratory Service
2016
University of North Dakota
2016
University of South Dakota
2016
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 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...
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....
Despite the key role of γ-aminobutyric acid (GABA) neurons in modulation cerebral cortical output, little is known about their development human cortex. We analyzed several GABAergic parameters standardized regions cortex and white matter a total 38 fetuses infants from 19 gestational weeks to 2.7 postnatal years using immunocytochemistry, Western blotting, tissue autoradiography, computer-based cellular quantitation. At least 20% migrated toward over late gestation. After term, migration...
Traumatic coma is associated with disruption of axonal pathways throughout the brain, but specific involved in humans are incompletely understood. In this study, we used high angular resolution diffusion imaging to map connectivity that mediate 2 critical components consciousness-arousal and awareness-in postmortem brain a 62-year-old woman acute traumatic control brains. High tractography guided tissue sampling neuropathologic analysis. demonstrated complete white matter connecting...
The cellular basis of cognitive abnormalities in preterm infants with periventricular leukomalacia (PVL) is uncertain. One important possibility that damage to white matter and subplate neurons are critical the formation cerebral cortex occurs conjunction oligodendrocyte axonal injury PVL. We tested hypothesis overall density region significantly lower PVL cases compared non-PVL controls.We used a computer-based method for determination microtubule-associated protein 2-immunolabeled...
Sudden unexplained death in infants, including the sudden infant syndrome, is likely due to heterogeneous causes that involve different intrinsic vulnerabilities and/or environmental factors. Neuropathologic research focuses upon role of brain regions, particularly brainstem, regulate or modulate autonomic and respiratory control during sleep transitions waking. The hippocampus a key component forebrain–limbic network modulates autonomic/respiratory via brainstem connections, but its has...
Consciousness is composed of arousal (i.e., wakefulness) and awareness. Substantial progress has been made in mapping the cortical networks that underlie awareness human brain, but knowledge about subcortical sustain humans incomplete. Here, we aimed to map connectivity a proposed network sustains wakefulness analogous default mode (DMN) shown contribute We integrated data from ex vivo diffusion magnetic resonance imaging (MRI) three brains, obtained at autopsy neurologically normal...
Periventricular leukomalacia (PVL) involves free radical injury to developing oligodendrocytes (OLs), resulting from ischemia/reperfusion, particularly between 24 and 32 gestational weeks. Using immunocytochemistry Western blots, we tested the hypothesis that this vulnerability toxicity results, in part, developmental lack of superoxide dismutases (SOD)-1 -2, catalase, glutathione peroxidase (GPx) telencephalic white matter human fetus. During period greatest PVL risk through term (≥37...
Abstract The role of the cerebral cortex in cognitive deficits preterm survivors is poorly understood. Periventricular leukomalacia (PVL), key feature encephalopathy prematurity, characterized by periventricular necrotic foci and diffuse gliosis surrounding white matter. Here, we tested hypothesis that reductions density layer I neurons and/or pyramidal layers III V are associated with PVL, indicating cortical pathology potentially long‐term survivors. In controls (23 gestational weeks to 18...
Sudden infant death syndrome (SIDS) is the leading cause of postneonatal mortality. Although rate has plateaued, any unexpected an a family tragedy thus finding causes and contributors to risk remains major public health concern. The primary objective this investigation was determine patterns drinking smoking during pregnancy that increase SIDS.The Safe Passage Study prospective, multi-center, observational study with 10,088 women, 11,892 pregnancies, 12,029 fetuses, followed 1-year post...
Sudden infant death syndrome (SIDS), the leading cause of postneonatal mortality, likely comprises heterogeneous disorders with common phenotype sudden without explanation upon postmortem investigation. Previously, we reported that ∼40% SIDS deaths are associated abnormalities in serotonin (5-hydroxytryptamine, 5-HT) regions brainstem critical homeostatic regulation. Here tested hypothesis is an alteration serum 5-HT levels. Serum 5-HT, adjusted for postconceptional age, was significantly...
This study aimed to evaluate genetic contributions sudden unexpected death in pediatrics (SUDP).We phenotyped and performed exome sequencing for 352 SUDP cases. We analyzed variants 294 "SUDP genes" with mechanisms plausibly related death. In a subset of 73 cases parental data (trios), we exome-wide analyses conducted cohort-wide burden analyses.In total, identified likely contributory 37 probands (11%). Analysis genes pathogenic/likely pathogenic 12 (SCN1A, DEPDC5 [2], GABRG2, SCN5A TTN...
1. Phosphorylation of caldesmon was assayed in canine colonic circular smooth muscle strips labelled with 32P and stimulated 10 microM acetylcholine. Caldesmon isolated by two‐dimensional non‐equilibrium pH gel electrophoresis. Stimulation acetylcholine increased phosphorylation significantly from a basal level 0.6 +/‐ 0.07 to 1.1 0.15 mol P1 (mol caldesmon)‐1 after 2 min. 2. MAP kinase activities were measured SDS extracts reconstitution method using myelin basic protein. Myelin protein...
Periventricular leukomalacia (PVL), the major lesion underlying cerebral palsy in survivors of prematurity, is characterized by focal periventricular necrosis and diffuse gliosis immature white matter. Causal roles have been ascribed to hypoxiaischemia maternal-fetal infection, leading cytokine responses, inflammation, oligodendrocyte cell death. Because interferon-gamma (IFN-gamma) directly toxic oligodendrocytes, we tested hypothesis that it expressed PVL (N = 13) compared age-adjusted...
High angular resolution diffusion imaging (HARDI) demonstrates transient radial coherence of telencephalic white matter in the human fetus. Our objective was to define neuroanatomic basis this through correlative HARDI- and postmortem tissue analyses. Applying immunomarkers glial fibers (RGFs), axons, blood vessels 18 cases (19 gestational weeks 3 postnatal years), we compared their developmental profiles HARDI tractography brains comparable ages (n = 11). At midgestation, corresponded with...