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Joseph J. Volpe - One of the best experts on this subject based on the ideXlab platform.
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Neonatal encephalitis and White Matter Injury: More than just inflammation?
Annals of neurology, 2008Co-Authors: Joseph J. VolpeAbstract:In this issue of the Annals, Verboon-Maciolek and coworkers show that human parechovirus (HPeV), specifically HPeV3, is an important cause of neonatal viral encephalitis.1 The six serotypes of HPeVs that are included in the genus Parechovirus are small single-stranded (ss) RNA viruses belonging to the family Picornaviridae.2, 3 These viruses bear many similarities with another and better-known Picornaviridae genus, Enterovirus (EV). Indeed, the genus Parechovirus began with the reclassification of echovirus 21 and 22 as HPeV1 and HPeV2 because of molecular and genetic differences from the remainder of EV. These differences are important because they explain, in part, why the usual polymerase chain reaction (PCR) testing for EV does not detect HPeV. Thus encephalitic infection by HPeV3 has been overlooked in the past, one important point of the current article. (Neonatal encephalitis by other HPeV subtypes is extremely rare and not discussed further.) The encephalitis caused by HPeV3 infection as well as by EV is associated with neonatal seizures and with apparent cerebral White Matter Injury.1, 4 The current report has important implications concerning the etiology of neonatal viral encephalitis, the differential diagnosis of neonatal seizures, and the pathology and pathophysiology of the White Matter Injury.
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Pathogenesis of cerebral White Matter Injury of prematurity
Archives of disease in childhood. Fetal and neonatal edition, 2007Co-Authors: Omar Khwaja, Joseph J. VolpeAbstract:Cerebral White Matter Injury, characterised by loss of premyelinating oligodendrocytes (pre-OLs), is the most common form of Injury to the preterm brain and is associated with a high risk of neurodevelopmental impairment. The unique cerebrovascular anatomy and physiology of the premature baby underlies the exquisite sensitivity of White Matter to the abnormal milieu of preterm extrauterine life, in particular ischaemia and inflammation. These two upstream mechanisms can coexist and amplify their effects, leading to activation of two principal downstream mechanisms: excitotoxicity and free radical attack. Upstream mechanisms trigger generation of reactive oxygen and nitrogen species. The pre-OL is intrinsically vulnerable to free radical attack due to immaturity of antioxidant enzyme systems and iron accumulation. Ischaemia and inflammation trigger glutamate receptor-mediated Injury leading to maturation-dependent cell death and loss of cellular processes. This review looks at recent evidence for pathogenetic mechanisms in White Matter Injury with emphasis on targets for prevention and treatment of Injury.
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Cerebral White Matter Injury in the newborn following Escherichia coli meningitis
European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society, 2004Co-Authors: Divyen K Shah, Joseph J. Volpe, Andrew J. Daley, Rod W. Hunt, Terrie E. InderAbstract:MR findings from six newborns with Escherichia coli (E. coli) meningitis are reported. Five of the six infants were infected with the K1 strain. All the infants displayed significant White Matter Injury on MR imaging. E. coli remains a serious cause of meningitis and MR imaging in this case series provides additional important information highlighting the vulnerability of the cerebral White Matter in this condition in the newborn infant.
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The relationship of CSF and plasma cytokine levels to cerebral White Matter Injury in the premature newborn.
Pediatric research, 2004Co-Authors: Vanessa J Ellison, Brian A Darlow, Joseph J. Volpe, Tessa J. Mocatta, Christine C. Winterbourn, Terrie E. InderAbstract:Ischemia and systemic infection are implicated in the etiology of periventricular White Matter Injury, a major cause of adverse motor and cognitive outcome in preterm infants. Cytokines are signaling proteins that can be produced as part of the inflammatory response to both ischemia and infection. The aim of this study was to relate cerebrospinal fluid (CSF) concentrations of IL-6, IL-8, IL-10, tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ) to magnetic resonance–defined White Matter Injury in preterm infants. Relationships between CSF and plasma cytokine concentrations were also examined. Preterm infants (≤32 wk) and more mature infants from The Royal Women's Hospital, Melbourne, Australia, and Christchurch Women's Hospital, Christchurch, New Zealand, were eligible for study if they required a clinically indicated lumbar puncture. Plasma samples were obtained in a subgroup of Christchurch infants. Preterm infants underwent advanced quantitative volumetric magnetic resonance imaging using a 1.5-Tesla scanner at term equivalent. One hundred forty-six infants were enrolled and 190 CSF and 42 plasma samples obtained. There was no significant correlation between paired CSF and plasma concentrations for any cytokine. In comparing plasma and CSF concentrations, levels of IL-8 were significantly higher in CSF than plasma. Preterm infants with MRI-defined cerebral White Matter Injury had higher levels of IL-6, IL-10, and TNF-α in the CSF than infants without such Injury. Plasma cytokine concentrations may not reflect CSF cytokine levels or inflammatory events within the brain. Elevated CSF levels of cytokines in infants with White Matter Injury suggest an altered inflammatory balance.
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cerebral White Matter Injury of the premature infant more common than you think
Pediatrics, 2003Co-Authors: Joseph J. VolpeAbstract:Brain Injury in the premature infant consists of multiple lesions, principally germinal matrix-intraventricular hemorrhage, posthemorrhagic hydrocephalus, and periventricular leukomalacia (PVL). The last of these now appears to be the most important determinant of the neurologic morbidity observed in survivors of birth weight <1500 g. Indeed, of these very low birth weight infants, ∼10% later exhibit cerebral palsy, and ∼50%, cognitive and behavioral deficits.1–5 The focal necrotic lesions of PVL deep in the cerebral White Matter correlate well with the cerebral palsy, whereas the cognitive/behavioral deficits may relate to more diffuse White Matter Injury observed with PVL (see below). The nature of the relationship between the diffuse White Matter Injury and the cognitive/behavioral deficits is complex and not entirely understood (see below). The current report of the Hammersmith group by Counsell et al,6 published elsewhere in this issue, addresses the frequency and magnetic resonance imaging (MRI) characteristics of this diffuse White Matter abnormality. The study of Counsell et al6 stimulates further a necessary change in the widely held concept of PVL as principally focal necrotic lesions in the periventricular White Matter with subsequent cyst formation. This concept is based on the earlier classic neuropathological description in 1962 of the focal necrotic lesions by Banker and Larroche.7 That landmark work led to the appropriate descriptive term for focal softening in the periventricular White Matter, ie, PVL. Indeed, innumerable later in vivo clinical and epidemiologic studies of PVL published in the last decade or so have used the ultrasonographic finding of focal periventricular echolucency as the hallmark of PVL (see ref. 1 for review). However, focal necrotic lesions evolving to cysts, readily identified by cranial ultrasonography, are no longer the principal feature of White Matter Injury in premature infants. Cystic PVL identified by brain imaging is a … Reprints requests to (J.J.V.) Department of Neurology, Fegan 1103, Children’s Hospital, 300 Longwood Ave, Boston, MA 02115. E-mail: joseph.volpe{at}tch.harvard.edu
Richard F Keep - One of the best experts on this subject based on the ideXlab platform.
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The effect of age-related risk factors and comorbidities on White Matter Injury and repair after ischemic stroke.
Neurobiology of disease, 2018Co-Authors: Michael M. Wang, Richard F Keep, Yanqin Gao, Yejie ShiAbstract:Abstract White Matter Injury is a crucial component of human stroke, but it has often been neglected in preclinical studies. Most human stroke is associated with one or more comorbidities, including aging, hypertension, diabetes and metabolic syndrome including hyperlipidemia. The purpose of this review is to examine how age and hypertension impact stroke-induced White Matter Injury as well as White Matter repair in both human stroke and preclinical models. It is essential that comorbidities be examined in preclinical trials as they may impact translatability to the clinic. In addition, understanding how comorbidities impact White Matter Injury and repair may provide new therapeutic opportunities for patients with those conditions.
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zinc protoporphyrin attenuates White Matter Injury after intracerebral hemorrhage
Acta Neurochirurgica, 2016Co-Authors: Y Gong, Wen Quan Liu, Richard F Keep, Ya HuaAbstract:Intracerebral hemorrhage (ICH)-induced White Matter Injury has not been well studied. The objective of this study was to examine the effect of zinc protoporphyrin (ZnPP) on White Matter Injury induced by ICH. This study was divided into two parts. In the first part, rats received either a needle insertion (sham) or 100 μl autologous blood into the right basal ganglia. The rats were euthanized at 1, 3, 7, 14, or 28 days later for myelin basic protein (MBP) measurement. In the second part, rats had intracerebral infusion of 100 μl autologous blood, and an intraperitoneal osmotic mini-pump was implanted immediately after ICH to deliver vehicle or ZnPP (1 nmol/h), a heme oxygenase inhibitor, for up to 14 days. Rats were euthanized at day 28 for MBP staining. The number of MBP-labeled fiber bundles and their area were determined. The time-course showed that the White Matter was lost in the ipsilateral basal ganglia from day 1 to day 28 after ICH. The number of MBP-labeled bundles and their area were significantly lower 2 weeks after ICH compared with sham-operated rats (p < 0.05). Systemic treatment with ZnPP attenuated the loss of MBP-labeled bundles (p < 0.01) and area (p < 0.01). In conclusion, marked White Matter Injury occurs after ICH. ZnPP reduces White Matter Injury, suggesting a role of heme degradation products in ICH-induced White Matter damage.
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White Matter Injury after subarachnoid hemorrhage role of blood brain barrier disruption and matrix metalloproteinase 9
Stroke, 2015Co-Authors: Yusuke Egashira, Richard F Keep, Hao Zhao, Guohua XiAbstract:Background and Purpose— We recently observed early White Matter Injury after experimental subarachnoid hemorrhage (SAH), but the underlying mechanisms are uncertain. This study investigated the potential role of matrix metalloproteinase (MMP)-9 in blood–brain barrier (BBB) disruption and consequent White Matter Injury. Methods— SAH was induced by endovascular perforation in adult male mice. The following 3 experiments were devised: (1) mice underwent magnetic resonance imaging at 24 h after SAH and were euthanized to determine BBB disruption and MMP-9 activation in White Matter; (2) to investigate the role of MMP-9 in BBB disruption, lesion volumes on magnetic resonance imaging were compared between wild-type (WT) and MMP-9 knockout (MMP-9−/−) mice at 24 h after SAH; (3) WT and MMP-9−/− mice underwent magnetic resonance imaging at 1 and 8 days after SAH to detect time-dependent changes in brain Injury. Brains were used to investigate myelin integrity in White Matter. Results— In WT mice with SAH, White Matter showed BBB disruption (albumin leakage) and T2 hyperintensity on magnetic resonance imaging. MMP-9 activity was elevated at 24 h after SAH. MMP-9−/− mice had less White Matter T2 hyperintensity after SAH than WT mice. At 8 days after SAH, WT mice had decreased myelin integrity and MMP-9−/− mice developed less White Matter Injury. Conclusions— SAH causes BBB disruption and consequent Injury in White Matter. MMP-9 plays an important role in those pathologies and could be a therapeutic target for SAH-induced White Matter Injury.
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acute White Matter Injury after experimental subarachnoid hemorrhage potential role of lipocalin 2
Stroke, 2014Co-Authors: Yusuke Egashira, Richard F Keep, Guohua XiAbstract:Background and Purpose—White Matter Injury occurs after subarachnoid hemorrhage (SAH) and has not been well studied. In this study, we investigated acute White Matter Injury in a mouse SAH model and the role of lipocalin 2 (LCN2) in that Injury. Methods—SAH was induced by endovascular perforation in wild-type (WT) or LCN2 knockout (LCN2−/−) mice. Sham WT mice underwent the same procedure without perforation. MRI was performed 24 hours after SAH and the volumes of the T2-hyperintensity in White Matter were measured. Immunohistochemistry was performed to determine White Matter Injury. Results—Mortality rates and SAH severity were not significantly different between WT and LCN2−/− animals. T2-hyperintensity in the White Matter was observed in all WT animals at 24 hours after SAH (6.1±2.7 versus 0.06±0.07 mm3 in sham; P<0.001), and the volume of T2-hyperintensity tended to correlate with SAH severity (r=0.30; P=0.055). In WT animals with SAH, numerous LCN2-positive cells were observed in White Matter. In cont...
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Acute White Matter Injury After Experimental Subarachnoid Hemorrhage Potential Role of Lipocalin 2
Stroke, 2014Co-Authors: Yusuke Egashira, Ya Hua, Richard F KeepAbstract:Background and Purpose—White Matter Injury occurs after subarachnoid hemorrhage (SAH) and has not been well studied. In this study, we investigated acute White Matter Injury in a mouse SAH model and the role of lipocalin 2 (LCN2) in that Injury. Methods—SAH was induced by endovascular perforation in wild-type (WT) or LCN2 knockout (LCN2−/−) mice. Sham WT mice underwent the same procedure without perforation. MRI was performed 24 hours after SAH and the volumes of the T2-hyperintensity in White Matter were measured. Immunohistochemistry was performed to determine White Matter Injury. Results—Mortality rates and SAH severity were not significantly different between WT and LCN2−/− animals. T2-hyperintensity in the White Matter was observed in all WT animals at 24 hours after SAH (6.1±2.7 versus 0.06±0.07 mm3 in sham; P
Terrie E. Inder - One of the best experts on this subject based on the ideXlab platform.
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Effects of White Matter Injury on resting state fMRI measures in prematurely born infants.
PloS one, 2013Co-Authors: Christopher D. Smyser, Abraham Z. Snyder, Joshua S. Shimony, Tyler Blazey, Terrie E. Inder, Jeffrey J. NeilAbstract:The cerebral White Matter is vulnerable to Injury in very preterm infants (born prior to 30 weeks gestation), resulting in a spectrum of lesions. These range from severe forms, including cystic periventricular leukomalacia and periventricular hemorrhagic infarction, to minor focal punctate lesions. Moderate to severe White Matter Injury in preterm infants has been shown to predict later neurodevelopmental disability, although outcomes can vary widely in infants with qualitatively comparable lesions. Resting state functional connectivity magnetic resonance imaging has been increasingly utilized in neurodevelopmental investigations and may provide complementary information regarding the impact of White Matter Injury on the developing brain. We performed resting state functional connectivity magnetic resonance imaging at term equivalent postmenstrual age in fourteen preterm infants with moderate to severe White Matter Injury secondary to periventricular hemorrhagic infarction. In these subjects, resting state networks were identifiable throughout the brain. Patterns of aberrant functional connectivity were observed and depended upon Injury severity. Comparisons were performed against data obtained from prematurely-born infants with mild White Matter Injury and healthy, term-born infants and demonstrated group differences. These results reveal structural-functional correlates of preterm White Matter Injury and carry implications for future investigations of neurodevelopmental disability.
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Cerebral White Matter Injury in the newborn following Escherichia coli meningitis
European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society, 2004Co-Authors: Divyen K Shah, Joseph J. Volpe, Andrew J. Daley, Rod W. Hunt, Terrie E. InderAbstract:MR findings from six newborns with Escherichia coli (E. coli) meningitis are reported. Five of the six infants were infected with the K1 strain. All the infants displayed significant White Matter Injury on MR imaging. E. coli remains a serious cause of meningitis and MR imaging in this case series provides additional important information highlighting the vulnerability of the cerebral White Matter in this condition in the newborn infant.
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The relationship of CSF and plasma cytokine levels to cerebral White Matter Injury in the premature newborn.
Pediatric research, 2004Co-Authors: Vanessa J Ellison, Brian A Darlow, Joseph J. Volpe, Tessa J. Mocatta, Christine C. Winterbourn, Terrie E. InderAbstract:Ischemia and systemic infection are implicated in the etiology of periventricular White Matter Injury, a major cause of adverse motor and cognitive outcome in preterm infants. Cytokines are signaling proteins that can be produced as part of the inflammatory response to both ischemia and infection. The aim of this study was to relate cerebrospinal fluid (CSF) concentrations of IL-6, IL-8, IL-10, tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ) to magnetic resonance–defined White Matter Injury in preterm infants. Relationships between CSF and plasma cytokine concentrations were also examined. Preterm infants (≤32 wk) and more mature infants from The Royal Women's Hospital, Melbourne, Australia, and Christchurch Women's Hospital, Christchurch, New Zealand, were eligible for study if they required a clinically indicated lumbar puncture. Plasma samples were obtained in a subgroup of Christchurch infants. Preterm infants underwent advanced quantitative volumetric magnetic resonance imaging using a 1.5-Tesla scanner at term equivalent. One hundred forty-six infants were enrolled and 190 CSF and 42 plasma samples obtained. There was no significant correlation between paired CSF and plasma concentrations for any cytokine. In comparing plasma and CSF concentrations, levels of IL-8 were significantly higher in CSF than plasma. Preterm infants with MRI-defined cerebral White Matter Injury had higher levels of IL-6, IL-10, and TNF-α in the CSF than infants without such Injury. Plasma cytokine concentrations may not reflect CSF cytokine levels or inflammatory events within the brain. Elevated CSF levels of cytokines in infants with White Matter Injury suggest an altered inflammatory balance.
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Lowered electroencephalographic spectral edge frequency predicts the presence of cerebral White Matter Injury in premature infants.
Pediatrics, 2003Co-Authors: Terrie E. Inder, Liz Buckland, Chris E. Williams, Carole Spencer, Mark I. Gunning, Brian A Darlow, Joseph J. Volpe, Peter D. GluckmanAbstract:Objective. Current methods for early identification of cerebral White Matter Injury in the premature infant at the bedside are inadequate. This study investigated the utility of advanced spectral analysis of the neonatal electroencephalogram (EEG) in the early diagnosis of White Matter Injury in the premature infant. The critical measurement used, suggested largely by previous studies in animal models, was the spectral edge frequency (SEF), calculated here as the frequency below which 90% of the power in the EEG exists. Methods. Fifty-nine very low birth weight infants (87% of eligible infants) had electrodes placed over the central and parietal regions (C3, P3, C4, and P4 sites according to the 10-20 international system) for the collection of EEG amplitude, intensity, and SEF. All averaged signals were analyzed off-line using software (Chart Analyzer; BrainZ Instruments, Auckland, NZ). All infants had a magnetic resonance imaging scan at term to identify the presence and severity of White Matter Injury. Results. There was no significant difference between conventional EEG amplitude and intensity for infants with or without evidence of White Matter Injury. However, premature infants with increasingly severe White Matter Injury had progressively lower SEFs compared with infants who did not exhibit White Matter Injury. Conclusions. These data suggest that SEF-based measures are useful for defining the presence and severity of White Matter Injury at the bedside.
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Elevated free radical products in the cerebrospinal fluid of VLBW infants with cerebral White Matter Injury.
Pediatric research, 2002Co-Authors: Terrie E. Inder, Carole Spencer, Brian A Darlow, Joseph J. Volpe, Tessa J. Mocatta, Christine C. WinterbournAbstract:Free radical mediated cellular Injury has been hypothesized to play a key role in the pathogenesis of White Matter Injury in the premature infant, although direct evidence is lacking. Between April 1999 and May 2001, 22 very low birthweight infants, 30 term infants, and 17 adults had samples of cerebrospinal fluid (CSF) collected for clinical indications. Only CSF samples without any evidence of meningeal inflammation were analyzed for the levels of the lipid peroxidation products, 8-isoprostane and malondialdehyde (MDA), and protein carbonyls as a measure of protein oxidation. Chlorotyrosine was monitored as a measure of neutrophil oxidative activity. In the premature infants with subsequent evidence of White Matter Injury on magnetic resonance imaging at term, there was a significant elevation in the CSF level of protein carbonyls in comparison with the level in healthy premature infants, term infants, and adult controls (all p < 0.001). A significant difference in the levels of the lipid peroxidation products, 8-isoprostane and MDA, was apparent between premature infants with White Matter Injury and adult controls (isoprostanes p = 0.02, MDA p = 0.014). There was a trend toward higher levels of 8-isoprostane in the premature infants with White Matter Injury in comparison with those without White Matter Injury (p = 0.08), with 5 of the 14 infants with White Matter Injury having levels that were more than 10-fold higher than the top of the adult range. There was no significant difference in the level of chlorotyrosines among any of the groups. These preliminary data provide evidence of an association of elevated oxidative products during the evolution of White Matter Injury in the human premature infant.
Steven P. Miller - One of the best experts on this subject based on the ideXlab platform.
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Fetal brain growth and risk of postnatal White Matter Injury in critical congenital heart disease.
The Journal of thoracic and cardiovascular surgery, 2020Co-Authors: Shabnam Peyvandi, A. James Barkovich, Steven P. Miller, Jessie Mei Lim, Davide Marini, V. Mohan Reddy, Patrick S. Mcquillen, Mike SeedAbstract:Abstract Objective To test the hypothesis that delayed brain development in fetuses with d-transposition of the great arteries or hypoplastic left heart syndrome heightens their postnatal susceptibility to acquired White Matter Injury. Methods This is a cohort study across 3 sites. Subjects underwent fetal (third trimester) and neonatal preoperative magnetic resonance imaging of the brain to measure total brain volume as a measure of brain maturity and the presence of acquired White Matter Injury after birth. White Matter Injury was categorized as no-mild or moderate-severe based on validated grading criteria. Comparisons were made between the Injury groups. Results A total of 63 subjects were enrolled (d-transposition of the great arteries: 37; hypoplastic left heart syndrome: 26). White Matter Injury was present in 32.4% (n = 12) of d-transposition of the great arteries and 34.6% (n = 8) of those with hypoplastic left heart syndrome. Overall total brain volume (taking into account fetal and neonatal scan) was significantly lower in those with postnatal moderate-severe White Matter Injury compared with no-mild White Matter Injury after adjusting for age at scan and site in d-transposition of the great arteries (coefficient: 14.8 mL, 95% confidence interval, −28.8 to −0.73, P = .04). The rate of change in total brain volume from fetal to postnatal life did not differ by Injury group. In hypoplastic left heart syndrome, no association was noted between overall total brain volume and change in total brain volume with postnatal White Matter Injury. Conclusions Lower total brain volume beginning in late gestation is associated with increased risk of postnatal moderate-severe White Matter Injury in d-transposition of the great arteries but not hypoplastic left heart syndrome. Rate of brain growth was not a risk factor for White Matter Injury. The underlying fetal and perinatal physiology has different implications for postnatal risk of White Matter Injury.
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Infection and White Matter Injury in infants with congenital cardiac disease
Cardiology in the young, 2011Co-Authors: Hannah C. Glass, Chelsea Bowman, Vann Chau, Alisha Moosa, Adam L. Hersh, Andrew Campbell, Kenneth J. Poskitt, Anthony Azakie, A. James Barkovich, Steven P. MillerAbstract:More than 60% of newborns with severe congenital cardiac disease develop perioperative brain injuries. Known risk factors include: pre-operative hypoxemia, cardiopulmonary bypass characteristics, and post-operative hypotension. Infection is an established risk factor for White Matter Injury in premature newborns. In this study, we examined term infants with congenital cardiac disease requiring surgical repair to determine whether infection is associated with White Matter Injury. Acquired infection was specified by site - bloodstream, pneumonia, or surgical site infection - according to strict definitions. Infection was present in 23 of 127 infants. Pre- and post-operative imaging was evaluated for acquired Injury by a paediatric neuroradiologist. Overall, there was no difference in newly acquired post-operative White Matter Injury in infants with infection (30%), compared to those without (31%). When stratified by anatomy, infants with transposition of the great arteries, and bloodstream infection had an estimated doubling of risk of White Matter Injury that was not significant, whereas those with single ventricle anatomy had no apparent added risk. When considering only infants without stroke, the estimated association was higher, and became significant after adjusting for duration of inotrope therapy. In this study, nosocomial infection was not associated with White Matter Injury. Nonetheless, when controlling for risk factors, there was an association between bloodstream infection and White Matter Injury in selected sub-populations. Infection prevention may have the potential to mitigate long-term neurologic impairment as a consequence of White Matter Injury, which underscores the importance of attention to infection control for these patients.
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Differential effects of intraventricular hemorrhage and White Matter Injury on preterm cerebellar growth.
The Journal of pediatrics, 2010Co-Authors: Emily W.y. Tam, Vann Chau, Kenneth J. Poskitt, Steven P. Miller, David V. Glidden, Donna M. Ferriero, Colin Studholme, A. James BarkovichAbstract:Objective To hypothesize that detailed examination of early cerebellar volumes in time would distinguish differences in cerebellar growth associated with intraventricular hemorrhage (IVH) and White Matter Injury in preterm infants. Study design Preterm newborns at the University of California San Francisco (n = 57) and the University of British Columbia (n = 115) were studied with serial magnetic resonance imaging scans near birth and again at near term-equivalent age. Interactive semi-automated tools were used to determine volumes of the cerebellar hemispheres. Results Adjusting for supratentorial brain Injury, cerebellar hemorrhage, and study site, cerebellar volume increased 1.7 cm 3 /week postmenstrual age (95% CI, 1.6-1.7; P P 3 lower in premature infants with grade 1 to 2 IVH and 5.4 cm 3 lower in infants with grade 3 to 4 IVH. The same magnitude of decrease was found between ipsilateral and contralateral IVH. No association was found with severity of White Matter Injury ( P = .3). Conclusions Early effects of decreased cerebellar volume associated with supratentorial IVH in either hemisphere may be a result of concurrent cerebellar Injury or direct effects of subarachnoid blood on cerebellar development.
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Recurrent postnatal infections are associated with progressive White Matter Injury in premature infants.
Pediatrics, 2008Co-Authors: Hannah C. Glass, Vann Chau, Kenneth J. Poskitt, A. James Barkovich, Sonia L. Bonifacio, David V. Glidden, Donna M. Ferriero, Steven P. MillerAbstract:OBJECTIVE. Our objective was to identify clinical predictors of progressive White Matter Injury. METHODS. We evaluated 133 infants of RESULTS. Twelve neonates (9.0%) had progressive White Matter Injury. In the unadjusted analysis of 10 newborns without Candida meningoencephalitis, recurrent culture-positive postnatal infection and chronic lung disease were associated with progressive White Matter Injury. Exposure to multiple episodes of culture-positive infection significantly increased the risk of progressive White Matter Injury. Of the 11 neonates with >1 infection, 36.4% (4 infants) had progressive Injury, compared with 5.0% (6 infants) of those with ≤1 infection. Of the 35 infants with chronic lung disease, 17.1% (6 infants) had progressive Injury, compared with 4.3% (4 infants) of those without chronic lung disease. After adjustment for gestational age at birth, the association between infection and White Matter Injury persisted, whereas chronic lung disease was no longer a statistically significant risk factor. CONCLUSIONS. Recurrent postnatal infection is an important risk factor for progressive White Matter Injury in premature infants. This is consistent with emerging evidence that White Matter Injury is attributable to oligodendrocyte precursor susceptibility to inflammation, hypoxia, and ischemia.
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White Matter Injury is associated with impaired gaze in premature infants
Pediatric neurology, 2008Co-Authors: Hannah C. Glass, A. James Barkovich, David V. Glidden, Donna M. Ferriero, Shinji Fujimoto, Camilla Ceppi-cozzio, Agnes I. Bartha, Daniel B. Vigneron, Steven P. MillerAbstract:Periventricular leukomalacia is a risk factor for visual impairment in children born prematurely. The impact of diffuse White-Matter Injury, as detected on magnetic resonance imaging, on early visual function is unknown. We developed two 5-point visual-gaze scores to analyze the association between this clinical assessment and White-Matter Injury in 93 premature neonates P
Iraj Ragerdi Kashani - One of the best experts on this subject based on the ideXlab platform.
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In utero transplantation of neural stem cells ameliorates maternal inflammation-induced prenatal White Matter Injury.
Journal of cellular biochemistry, 2019Co-Authors: Maryam Borhani-haghighi, Yousef Mohamadi, Iraj Ragerdi KashaniAbstract:Prenatal White Matter Injury is a serious problem due to maternal inflammation leading to postnatal disabilities. In this study, we used the periventricular leukomalacia (PVL) model as a common prenatal White Matter Injury by maternal administration of lipopolysaccharide (LPS). Neural stem cells (NSCs) have shown therapeutic ability in neurological disorders through a different mechanism such as immunomodulation. Here, we studied the preventive potential of NSCs following in utero transplantation into the embryonic lateral ventricle in an LPS-induced White Matter Injury model. Pregnant animals were divided into three groups and received phosphate buffered saline, LPS, or LPS + NSCs. The brains of offspring were obtained and evaluated by real-time polymerase chain reaction (PCR), immunohistochemy, enzyme-linked immunosorbent assay (ELISA), terminal deoxynucleotidyl transferase-mediated biotinylated-dUTP nick-end labeling (TUNEL), and caspase-3 activity assay. The LPS-induced maternal inflammation degenerated the myelin sheath in the offspring periventricular region which was associated with an increased microglial number, oligodendrocytes degeneration, proinflammatory cytokine secretion, and cell apoptosis. The transplanted NSCs homed into the brain and ameliorated the evaluated parameters. The expression of proinflammatory cytokines interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α), cell apoptosis and caspase-3 activity were inhibited by NSCs. In addition, Olig2 and myelin basic protein immunohistochemy staining showed that prenatal NSCs transplantation augmented the myelination in the periventricular White Matter of offspring. In conclusion, we think that prenatal therapeutic strategies, such as in utero NSCs transplantation, may prevent prenatal White Matter Injury after birth.