Abstract:
:Preterm birth is an important cause of perinatal brain injury (PBI). Neurological injury in extremely preterm infants often begins in utero with chorioamnionitis (CHORIO) or inflammation/infection of the placenta and concomitant placental insufficiency. Studies in humans have shown dysregulated inflammatory signaling throughout the placental-fetal brain axis and altered peripheral immune responses in children born preterm with cerebral palsy (CP). We hypothesized that peripheral immune responses would be altered in our well-established rat model of CP. Specifically, we proposed that isolated peripheral blood mononuclear cells (PBMCs) would be hyperresponsive to a second hit of inflammation throughout an extended postnatal time course. Pregnant Sprague-Dawley dams underwent a laparotomy on embryonic day 18 (E18) with occlusion of the uterine arteries (for 60 min) followed by intra-amniotic injection of lipopolysaccharide (LPS, 4 μg/sac) to induce injury in utero. Shams underwent laparotomy only, with equivalent duration of anesthesia. Laparotomies were then closed, and the rat pups were born at E22. PBMCs were isolated from pups on postnatal day 7 (P7) and P21, and subsequently stimulated in vitro with LPS for 3 or 24 h. A secreted inflammatory profile analysis of conditioned media was performed using multiplex electrochemiluminescent immunoassays, and the composition of inflammatory cells was assayed with flow cytometry (FC). Results indicate that CHORIO PBMCs challenged with LPS are hyperreactive and secrete significantly more tumor necrosis factor α (TNFα) and C-X-C chemokine ligand 1 at P7. FC confirmed increased intracellular TNFα in CHORIO pups at P7 following LPS stimulation, in addition to increased numbers of CD11b/c immunopositive myeloid cells. Notably, TNFα secretion was sustained until P21, with increased interleukin 6, concomitant with increased expression of integrin β1, suggesting both sustained peripheral immune hyperreactivity and a heightened activation state. Taken together, these data indicate that in utero injury primes the immune system and augments enhanced inflammatory signaling. The insidious effects of primed peripheral immune cells may compound PBI secondary to CHORIO and/or placental insufficiency, and thereby render the brain susceptible to future chronic neurological disease. Further understanding of inflammatory mechanisms in PBI may yield clinically important biomarkers and facilitate individualized repair strategies and treatments.
journal_name
Dev Neuroscijournal_title
Developmental neuroscienceauthors
Yellowhair TR,Noor S,Mares B,Jose C,Newville JC,Maxwell JR,Northington FJ,Milligan ED,Robinson S,Jantzie LLdoi
10.1159/000497273subject
Has Abstractpub_date
2019-03-28 00:00:00pages
1-11eissn
0378-5866issn
1421-9859pii
000497273pub_type
杂志文章abstract::Disorders primarily affecting the nervous system comprise approximately one third of all established Mendelian genetic diseases in man. Recombinant DNA technology provides new approaches to the diagnosis and elucidation of the molecular pathology of these disorders. For a small but increasing number of disorders the D...
journal_title:Developmental neuroscience
pub_type: 杂志文章,评审
doi:10.1159/000112346
更新日期:1983-01-01 00:00:00
abstract::Cortex cerebri pieces from fetal donors were homologously and bilaterally grafted to the anterior eye chamber of adult albino rats. After intraocular maturation, presence of an external glial membrane, glial membranes surrounding blood vessels and cortical astrocytes was demonstrated using antisera raised against glia...
journal_title:Developmental neuroscience
pub_type: 杂志文章
doi:10.1159/000112703
更新日期:1982-01-01 00:00:00
abstract::In order to investigate the possible influence of norepinephrine (NE) on neuronal development, the effects of neonatal NE depletion on postnatally developing cell populations were characterized in (1) the normal mouse cerebellum, and (2) a cerebellar model system with delayed germinal cell development produced by neon...
journal_title:Developmental neuroscience
pub_type: 杂志文章
doi:10.1159/000112695
更新日期:1982-01-01 00:00:00
abstract::The kinetics and sodium-dependence of gamma-aminobutyric acid (GABA), hypotaurine and taurine uptake were analyzed in cerebral slices prepared from mice of different postnatal ages. The maximal velocities of transport (V) and the Km constants for the high-affinity uptake all decreased with age, whereas the development...
journal_title:Developmental neuroscience
pub_type: 杂志文章
doi:10.1159/000112354
更新日期:1983-01-01 00:00:00
abstract::When cells from the cerebellum of late-gestation rats were grown at low density (50-100 cells/mm2) in a three-dimensional culture system, they rapidly expressed morphological and electrophysiological properties of neurons. Growth and differentiation of the population of solitary neurons as a whole was statistically as...
journal_title:Developmental neuroscience
pub_type: 杂志文章
doi:10.1159/000111645
更新日期:1992-01-01 00:00:00
abstract::Neuron-specific enolase (NSE) is a unique form of the glycolytic enzyme, enolase, which, in the brain, is strictly localized in differentiated neurons and neuroendocrine cells. In this report evidence is presented that NSE is first seen in the cell bodies of developing chick auditory and vestibular neurons shortly aft...
journal_title:Developmental neuroscience
pub_type: 杂志文章
doi:10.1159/000112689
更新日期:1982-01-01 00:00:00
abstract::In the socially monogamous prairie vole, we have observed that small changes in early handling, as well as early hormonal manipulations can have long-lasting and sexually dimorphic effects on behavior. These changes may be mediated in part by changes in parental interactions with their young, acting on systems that re...
journal_title:Developmental neuroscience
pub_type: 杂志文章,评审
doi:10.1159/000216544
更新日期:2009-01-01 00:00:00
abstract::Birth asphyxia can result in sensory impairment, learning and memory deficits without gross brain injury and severe motor deficits. We developed a model of birth asphyxia resulting in mild neurological injury and cognitive impairment using a long-gestation species with precocial fetal development. Spiny mice (Acomys c...
journal_title:Developmental neuroscience
pub_type: 杂志文章
doi:10.1159/000251907
更新日期:2009-01-01 00:00:00
abstract::Maternal infection during pregnancy increases the risk of neurobehavioral problems in offspring. Evidence from rodent models indicates that the maternal immune response to infection can alter fetal brain development, particularly in the hippocampus. However, information on the effects of maternal viral infection on fe...
journal_title:Developmental neuroscience
pub_type: 杂志文章
doi:10.1159/000486850
更新日期:2018-01-01 00:00:00
abstract::Adult neuronal ceroid lipofuscinosis (NCL), also called Kufs' disease, is clinically distinct from the other NCLs. It is a rare condition which is difficult to diagnose. More than 50% of the reported cases of Kufs' disease are not adult NCL and correspond very likely to a heterogeneous spectrum of lipidoses. Various c...
journal_title:Developmental neuroscience
pub_type: 杂志文章,评审
doi:10.1159/000112182
更新日期:1991-01-01 00:00:00
abstract::Chick embryo retina neurons in culture extend neurites and form synapses. Seven different culture substrates were compared to determine which culture surface would produce the best neuronal survival and neurite extension. The order of survival of retina neurons during 7 days of culture is salt-precipitated collagen gr...
journal_title:Developmental neuroscience
pub_type: 杂志文章
doi:10.1159/000112705
更新日期:1982-01-01 00:00:00
abstract::We studied the developmental changes of soluble and membrane-bound protein kinases (EC 2.7.1.37) in rat brain and found that the elution profiles from a DEAE-cellulose column by NaCl of adenosine-3':5'-monophosphate (cyclic AMP) dependent protein kinase from cytosol were not significantly different in newborn (0.19 M ...
journal_title:Developmental neuroscience
pub_type: 杂志文章
doi:10.1159/000112450
更新日期:1979-01-01 00:00:00
abstract::Prenatal cocaine exposure results in behavioral abnormalities throughout development in rats, but little is known regarding the biological mechanisms underlying these abnormalities. Pregnant rats received subcutaneous twice-daily injections (1 ml/kg) of normal saline or 15 mg/kg of cocaine hydrochloride throughout ges...
journal_title:Developmental neuroscience
pub_type: 杂志文章
doi:10.1159/000069363
更新日期:2002-01-01 00:00:00
abstract::Glutamine synthesis, the major pathway of ammonia detoxification, and the intracellular concentration of organic osmolytes in primary astrocytes and F98 glioma cells were investigated with multinuclear magnetic resonance spectroscopy. Acute exposure to ammonia (3 h incubation with NH4Cl) raised the concentration of gl...
journal_title:Developmental neuroscience
pub_type: 杂志文章
doi:10.1159/000017339
更新日期:1998-01-01 00:00:00
abstract::Cultures of rat oligodendrocytes were used to test the possible role of the cerebellar soluble lectin (CSL) in myelin formation. Immunocytochemistry at the ultrastructural level showed that the lectin is present in the cytoplasm of the perikaryon of cultured oligodendrocytes and also on the plasma membrane of the cell...
journal_title:Developmental neuroscience
pub_type: 杂志文章
doi:10.1159/000111970
更新日期:1988-01-01 00:00:00
abstract::Traumatic brain injury (TBI) is the leading cause of death and disability in children. Evidence-based guidelines for the management of this population are available; however, the data highlight significant deficiencies with few treatment standards or guidelines. Considering the limited availability of resources, it is...
journal_title:Developmental neuroscience
pub_type: 杂志文章,评审
doi:10.1159/000094153
更新日期:2006-01-01 00:00:00
abstract::Cerebral metabolism is known to be highly dependent upon glucose utilisation. In the neonate, severe hypoglycaemia is now recognized to be associated with subsequent adverse neurodevelopment and in extremis glial and neuronal cell death. However, the level at which hypoglycaemia becomes clinically important is not wel...
journal_title:Developmental neuroscience
pub_type: 杂志文章,评审
doi:10.1159/000112124
更新日期:1994-01-01 00:00:00
abstract::Preadolescent animals display protracted hormonal stress responses mediated by the hypothalamic-pituitary-adrenal (HPA) axis compared to adults. Though the mechanisms that underlie this shift in stress reactivity are unknown, reduced glucocorticoid-dependent negative feedback on the HPA axis has been posited to contri...
journal_title:Developmental neuroscience
pub_type: 杂志文章
doi:10.1159/000362873
更新日期:2014-01-01 00:00:00
abstract::Neuroblastoma is a childhood cancer caused by the transformation of sympathoadrenal progenitors. By following the formation of tumors in homozygous TH-MYCN mice, an established mouse model of neuroblastoma, we were able to capture transformed cells prior to the formation of large, vascularized tumors in order to deter...
journal_title:Developmental neuroscience
pub_type: 杂志文章
doi:10.1159/000365281
更新日期:2014-01-01 00:00:00
abstract::There is an important unmet need to further improve the outcome of neonatal encephalopathy in term infants. Meta-analyses of large controlled trials now suggest that maternal magnesium sulfate (MgSO4) therapy is associated with a reduced risk of cerebral palsy and gross motor dysfunction after premature birth, but tha...
journal_title:Developmental neuroscience
pub_type: 杂志文章,评审
doi:10.1159/000362206
更新日期:2014-01-01 00:00:00
abstract::Excitotoxicity plays a key role during insults to the developing brain such as neonatal encephalopathy, stroke, and encephalopathy of prematurity. Such insults affect many thousands of infants each year. Excitotoxicity causes frank lesions due to cell death and gliosis and disturbs normal developmental process, leadin...
journal_title:Developmental neuroscience
pub_type: 杂志文章
doi:10.1159/000464131
更新日期:2017-01-01 00:00:00
abstract::Necrotizing enterocolitis (NEC) increases the risk of brain injury and impaired neurodevelopment. Rapid brain maturation prior to birth may explain why preterm brains are particularly vulnerable to serious infections. Using pigs as models, we hypothesized that preterm birth was associated with altered blood-cerebrospi...
journal_title:Developmental neuroscience
pub_type: 杂志文章
doi:10.1159/000488979
更新日期:2018-01-01 00:00:00
abstract::A leading hypothesis of the cause of neuronal death in Huntington's disease (HD) is excitotoxicity, in which subpopulations of striatal neurons are hypersensitive to glutamate release due to changes in postsynaptic N-methyl-D-aspartate receptors (NMDARs). In the present study we used RT-PCR methods on single cells and...
journal_title:Developmental neuroscience
pub_type: 杂志文章
doi:10.1159/000091921
更新日期:2006-01-01 00:00:00
abstract::It has been demonstrated that postweaning social isolation alters dendritic development in the medial prefrontal cortex (mPFC) of the rat. In addition, (-)-deprenyl, a monoamine oxidase B (MAO-B) inhibitor, promotes dendritic growth in prefrontocortical pyramidal cells. This study examined whether prefrontocortical de...
journal_title:Developmental neuroscience
pub_type: 杂志文章
doi:10.1159/000096413
更新日期:2007-01-01 00:00:00
abstract::We have previously shown that a single intracranial injection of apotransferrin (aTf) in neonatal rats produces an accelerated mylinogenesis and increases the expression of certain myelin proteins such as myelin basic protein (MBP). In the present work, we studied the effects of aTf upon oligodendrocyte progenitor cel...
journal_title:Developmental neuroscience
pub_type: 杂志文章
doi:10.1159/000064945
更新日期:2002-01-01 00:00:00
abstract::The metabolism of [1, 2-13C2] acetate via the tricarboxylic acid (TCA) cycle leads to the formation of a number of key mass isotopomers of glutamate. The distribution of these isotopomers which is a function of pyruvate carboxylase, pyruvate dehydrogenase and pyruvate recycling was used to determine the relative anapl...
journal_title:Developmental neuroscience
pub_type: 杂志文章
doi:10.1159/000111442
更新日期:1996-01-01 00:00:00
abstract::We have previously provided evidence that ferritin binds selectively to white matter tracts in adult mouse and human brains. In cell culture experiments, ferritin binding is specifically localized to oligodendrocytes. The goal of the present study is to test the hypothesis that the developmental pattern for ferritin b...
journal_title:Developmental neuroscience
pub_type: 杂志文章
doi:10.1159/000065704
更新日期:2002-01-01 00:00:00
abstract::Neonatal stroke leads to mortality and severe morbidity, but there is no effective treatment currently available. Erythropoietin (EPO) has been shown to promote cytoprotection and neurogenesis and decrease subventricular zone morphologic changes following brain injury. The long-term cellular response to EPO has not be...
journal_title:Developmental neuroscience
pub_type: 杂志文章
doi:10.1159/000105473
更新日期:2007-01-01 00:00:00
abstract::Oligodendrocyte precursor cells (OPCs) originate in multiple restricted regions of the developing central nervous system (CNS). Here, we focus on morphological changes of oligodendrocyte lineage cells and their cellular dynamics including cell motility and proliferation. Morphological studies with molecular markers fo...
journal_title:Developmental neuroscience
pub_type: 杂志文章
doi:10.1159/000048718
更新日期:2001-01-01 00:00:00
abstract::Developing neurons synthesize substantial quantities of membrane phospholipids in producing new synapses. We investigated the effects of maternal uridine (as uridine-5'-monophosphate) and docosahexaenoic acid supplementation on pups' brain phospholipids, synaptic proteins and dendritic spine densities. Dams consumed n...
journal_title:Developmental neuroscience
pub_type: 杂志文章
doi:10.1159/000193394
更新日期:2009-01-01 00:00:00