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Involvement of the subplate zone in preterm infants with periventricular white matter injury.

ABSTRACT: Studies of periventricular white matter injury (PWMI) in preterm infants suggest the involvement of the transient cortical subplate zone. We studied the cortical wall of noncystic and cystic PWMI cases and controls. Non-cystic PWMI corresponded to diffuse white matter lesions, the predominant injury currently detected by imaging. Glial cell populations were analyzed in post-mortem human frontal lobes from very preterm [24–29 postconceptional weeks (pcw)] and preterm infants (30–34 pcw) using immunohistochemistry for glial fibrillary acidic protein (GFAP), monocarboxylate transporter 1(MCT1), ionized calcium-binding adapter molecule 1 (Iba1), CD68 and oligodendrocyte lineage (Olig2). Glial activation extended into the subplate in non-cystic PWMI but was restricted to the white matter in cystic PWMI. Two major age-related and laminar differences were observed in non-cystic PWMI: in very preterm cases, activated microglial cells were increased and extended into the subplate adjacent to the lesion, whereas in preterm cases, an astroglial reaction was seen not only in the subplate but throughout the cortical plate. There were no differences in Olig2-positive pre-oligodendrocytes in the subplate inPWMI cases compared with controls. The involvement of gliosis in the deep subplate supports the concept of the complex cellular vulnerability of the subplate zone during the preterm period and may explain widespread changes in magnetic resonance signal intensity in early PWMI.

SUBMITTER: Pogledic I

PROVIDER: S-EPMC8029368 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Circular RNA expression alteration in peripheral blood of premature infants with periventricular white matter damage

Project description:Periventricular white matter damage (PWMD) is the principal pathological type of brain damage in premature. It causes irreversible damage to the overall function of the central nervous system resulting in cerebral palsy, convulsions, epilepsy, cognitive, motor dysfunction and other late effects. CircRNAs are participate in the biological processes underlying many nervous system diseases. However, the circRNA expression profile of peripheral venous blood of premature infants with PWMD is not completely understood. Three premature with white matter damage (PWMD group) and three infants without brain injury (Normal group) were enrolled. Peripheral venous blood was collected from both groups for extraction of RNA and circRNA sequencing was performed. The RNA-seq technique was used to screen the differentially expressed circRNA in peripheral blood of infants with PWMD. The accuracy of sequencing results was verified by quantitative reverse transcription polymerase chain reaction (q-PCR) to the differentially express partial circRNA in the sequencing results. Bioinformatics analysis of Host genes was performed with differential circRNA. TargetScan and Miranda were used to predict circRNA-binding miRNAs and mapped into a circRNA-miRNA co-expression network. There were 119 significantly different circRNAs as compared with premature without brain injury, along with 1 circRNA was up-regulated and 4 circRNAs were down-regulated expression in the PWMD group. Combined with the existing research results and bioinformatics analysis results after sequencing, it is suggested that circRNA may regulate the occurrence and development of white matter damage in premature infants by interacting with miRNA. This first study of its kind further identified the expression profile of circRNA in peripheral blood of premature with WMD, and provide a novel targets for further investigation about the molecular mechanisms underlying PWMD and potential therapeutic intervention.

2020-05-20 | GSE131475 | GEO

High Presence of Extracellular Hemoglobin in the Periventricular White Matter Following Preterm Intraventricular Hemorrhage.

Project description:Severe cerebral intraventricular hemorrhage (IVH) in preterm infants continues to be a major clinical problem, occurring in about 15-20% of very preterm infants. In contrast to other brain lesions the incidence of IVH has not been reduced over the last decade, but actually slightly increased. Currently over 50% of surviving infants develop post-hemorrhagic ventricular dilatation and about 35% develop severe neurological impairment, mainly cerebral palsy and intellectual disability. To date there is no therapy available to prevent infants from developing either hydrocephalus or serious neurological disability. It is known that blood rapidly accumulates within the ventricles following IVH and this leads to disruption of normal anatomy and increased local pressure. However, the molecular mechanisms causing brain injury following IVH are incompletely understood. We propose that extracellular hemoglobin is central in the pathophysiology of periventricular white matter damage following IVH. Using a preterm rabbit pup model of IVH the distribution of extracellular hemoglobin was characterized at 72 h following hemorrhage. Evaluation of histology, histochemistry, hemoglobin immunolabeling and scanning electron microscopy revealed presence of extensive amounts of extracellular hemoglobin, i.e., not retained within erythrocytes, in the periventricular white matter, widely distributed throughout the brain. Furthermore, double immunolabeling together with the migration and differentiation markers polysialic acid neural cell adhesion molecule (PSA-NCAM) demonstrates that a significant proportion of the extracellular hemoglobin is distributed in areas of the periventricular white matter with high extracellular plasticity. In conclusion, these findings support that extracellular hemoglobin may contribute to the pathophysiological processes that cause irreversible damage to the immature brain following IVH.

| S-EPMC4971438 | biostudies-literature

Metabolic maturation of white matter is altered in preterm infants.

Project description:Significant physiological switches occur at birth such as the transition from fetal parallel blood flow to a two-circuit serial system with increased arterial oxygenation of blood delivered to all organs including the brain. In addition, the extra-uterine environment exposes premature infants to a host of stimuli. These events could conceivably alter the trajectory of brain development in premature infants. We used in vivo magnetic resonance spectroscopy to measure absolute brain metabolite concentrations in term and premature-born infants without evidence of brain injury at equivalent post-conceptional age. Prematurity altered the developmental time courses of N-acetyl-aspartate, a marker for axonal and neuronal development, creatine, an energy metabolite, and choline, a membrane metabolite, in parietal white matter. Specifically, at term-equivalency, metabolic maturation in preterm infants preceded development in term infants, but then progressed at a slower pace and trajectories merged at ?340-370 post-conceptional days. In parieto/occipital grey matter similar trends were noticed but statistical significance was not reached. The timing of white matter development and synchronization of white matter and grey matter maturation in premature-born infants is disturbed. This may contribute to the greater risk of long-term neurological problems of premature infants and to their higher risk for white matter injury.

| S-EPMC3899075 | biostudies-literature

Correction: Metabolic Maturation of White Matter Is Altered in Preterm Infants

Project description: Not available

| S-EPMC3945060 | biostudies-literature

Periventricular white matter changes in idiopathic intracranial hypertension.

Project description:ObjectiveTo evaluate whether increased cerebrospinal fluid (CSF) pressure causes alteration of periventricular white matter (WM) microstructure in patients with idiopathic intracranial hypertension (IIH).MethodsIn a prospective study, patients with refractory chronic headache with and without IIH performed a neuroimaging study including 3T MRI, 3D Phase Contrast MR venography, and diffusion tensor imaging (DTI) of the brain. Whole-brain voxel-wise comparisons of DTI abnormalities of WM were performed using tract-based spatial statistics. A correlation analysis between DTI indices and CSF opening pressure, highest peak, and mean pressure was also performed in patients with IIH.ResultsWe enrolled 62 consecutive patients with refractory chronic headaches. Thirty-five patients with IIH, and 27 patients without increased intracranial pressure. DTI analysis revealed no fractional anisotropy changes, but decreased mean, axial, and radial diffusivity in body (IIHMD = 0.80 ± 0.04, non-IIHMD = 0.84 ± 0.4, IIHAD = 1.67 ± 0.07, non-IIHAD = 1.74 ± 0.05, IIHRD = 0.38 ± 0.04, non-IIHRD = 0.42 ± 0.05 [mm2/sec × 10-3]) of corpus callosum, and in right superior corona radiata (IIHMD = 0.75 ± 0.04, non-IIHMD = 0.79 ± 0.05, IIHAD = 1.19 ± 0.07, non-IIHAD = 1.28 ± 0.09, IIHRD = 0.59 ± 0.03, non-IIHRD = 0.53 ± 0.03 [mm2/sec × 10-3]) of 35 patients with IIH compared with 27 patients without increased intracranial pressure. DTI indices were negatively correlated with high CSF pressures (P < 0.05). After medical treatment, eight patients showed incremented MD in anterior corona radiata left and right and superior corona radiata right.ConclusionsThere is significant DTI alteration in periventricular WM microstructure of patients with IIH suggesting tissue compaction correlated with high CSF pressure. This periventricular WM change may be partially reversible after medical treatment.

| S-EPMC6389746 | biostudies-literature

Postnatal Subventricular Zone Injury Predicts Motor Impairment in Preterm Infants Following Intestinal Disease

Project description:Following intestinal perforation in neonatal mice there is an injury to the subventrcular zone stem cell niche. These files are the raw data from mouse SVZ in controls and mice with modeled instestinal perforation.

2023-09-27 | GSE243778 | GEO

Postnatal Subventricular Zone Injury Predicts Motor Impairment in Preterm Infants Following Intestinal Disease

Project description:Following intestinal perforation in neonatal mice there is an injury to the subventrcular zone stem cell niche. These files are the raw data from mouse brain sections, transecting SVZ in controls and mice with modeled instestinal perforation.

2024-01-24 | GSE254087 | GEO

Altered glutamatergic metabolism associated with punctate white matter lesions in preterm infants.

Project description:Preterm infants (?10% of all births) are at high-risk for long-term neurodevelopmental disabilities, most often resulting from white matter injury sustained during the neonatal period. Glutamate excitotoxicity is hypothesized to be a key mechanism in the pathogenesis of white matter injury; however, there has been no in vivo demonstration of glutamate excitotoxicity in preterm infants. Using magnetic resonance spectroscopy (MRS), we tested the hypothesis that glutamate and glutamine, i.e., markers of glutamatergic metabolism, are altered in association with punctate white matter lesions and "diffuse excessive high signal intensity" (DEHSI), the predominant patterns of preterm white matter injury. We reviewed all clinically-indicated MRS studies conducted on preterm infants at a single institution during a six-year period and determined the absolute concentration of glutamate, glutamine, and four other key metabolites in the parietal white matter in 108 of those infants after two investigators independently evaluated the studies for punctate white matter lesions and DEHSI. Punctate white matter lesions were associated with a 29% increase in glutamine concentration (p?=?0.002). In contrast, there were no differences in glutamatergic metabolism in association with DEHSI. Severe DEHSI, however, was associated with increased lactate concentration (p?=?0.001), a marker of tissue acidosis. Findings from this study support glutamate excitotoxicity in the pathogenesis of punctate white matter lesions, but not necessarily in DEHSI, and suggest that MRS provides a useful biomarker for determining the pathogenesis of white matter injury in preterm infants during a period when neuroprotective agents may be especially effective.

| S-EPMC3582631 | biostudies-literature

Nutritional Intake, White Matter Integrity, and Neurodevelopment in Extremely Preterm Born Infants.

Project description:Determining optimal nutritional regimens in extremely preterm infants remains challenging. This study aimed to evaluate the effect of a new nutritional regimen and individual macronutrient intake on white matter integrity and neurodevelopmental outcome. Two retrospective cohorts of extremely preterm infants (gestational age < 28 weeks) were included. Cohort B (n = 79) received a new nutritional regimen, with more rapidly increased, higher protein intake compared to cohort A (n = 99). Individual protein, lipid, and caloric intakes were calculated for the first 28 postnatal days. Diffusion tensor imaging was performed at term-equivalent age, and cognitive and motor development were evaluated at 2 years corrected age (CA) (Bayley-III-NL) and 5.9 years chronological age (WPPSI-III-NL, MABC-2-NL). Compared to cohort A, infants in cohort B had significantly higher protein intake (3.4 g/kg/day vs. 2.7 g/kg/day) and higher fractional anisotropy (FA) in several white matter tracts but lower motor scores at 2 years CA (mean (SD) 103 (12) vs. 109 (12)). Higher protein intake was associated with higher FA and lower motor scores at 2 years CA (B = -6.7, p = 0.001). However, motor scores at 2 years CA were still within the normal range and differences were not sustained at 5.9 years. There were no significant associations with lipid or caloric intake. In extremely preterm born infants, postnatal protein intake seems important for white matter development but does not necessarily improve long-term cognitive and motor development.

| S-EPMC8539908 | biostudies-literature

Different patterns of punctate white matter lesions in serially scanned preterm infants.

Project description:Background and purposeWith the increased use of MRI in preterm infants, punctate white matter lesions (PWML) are more often recognized. The aim of this study was to describe the incidence and characteristics of these lesions as well as short-term outcome in a cohort of serially scanned preterm infants, using both conventional imaging, diffusion (DWI) and susceptibility (SWI) weighted imaging.Materials and methods112 preterm infants with 2 MRIs in the neonatal period, with evidence of punctate white matter lesions, were included. Appearance, lesion load, location, and abnormalities on DWI and SWI were scored and outcome data were collected.ResultsDifferent patterns of punctate white matter lesions did appear: a linear appearance associated with signal loss on SWI, and a cluster appearance associated with restricted diffusion on DWI on the first MRI. Cluster and mixed lesions on the first scan changed in appearance in over 50% on the second scan, whereas linear lesions generally kept their appearance. Lesions were only visible on the early scan in 33%, and were only seen at term equivalent age in 20%. Nine infants developed cerebral palsy, due to additional overt white matter lesions in six.ConclusionTwo patterns of punctate white matter lesions were identified: one with loss of signal on SWI in a linear appearance, and the other with DWI lesions with restricted diffusion in a cluster appearance. These different patterns are suggestive of a difference in underlying pathophysiology. To reliably classify PWML in the preterm infant in either pattern, an early MRI with DWI and SWI sequences is required.

| S-EPMC4184838 | biostudies-literature

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