Emerging Roles of miRNAs in Brain Development and Perinatal Brain Injury

: The central nervous system (CNS) is enriched with important classes of lipids, in which cholesterol is known to make up a major portion of myelin sheaths, besides being a structural and functional unit of CNS cell membranes. Unlike in the adult brain where the cholesterol pool is relatively stable, cholesterol is synthesized and accumulated at the highest rate in the developing brain to meet the needs of rapid brain growth at this stage, which is also a critical period for neuroplasticity. In addition to its biophysical role in membrane organization, cholesterol is crucial for brain development due to its involvement in brain patterning, myelination, neuronal differentiation and synaptogenesis. Thus any injuries to the immature brain that affect cholesterol homeostasis may have long-term adverse neurological consequences. In this review, we describe the unique features of brain cholesterol biosynthesis and metabolism, cholesterol trafficking between different cell types, and highlight cholesterol-dependent biological processes during brain maturation. We also discuss the association of impaired cholesterol homeostasis with several forms of perinatal brain disorders in term and preterm newborns, including hypoxic-ischemic encephalopathy. Strategies targeting the cholesterol pathways may open new avenues for diagnosis and treatment of developmental brain injury.

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Outcome at Age Five Years or Older for Children with Perinatal Brain Injury Treated with Neurohabilitation or Neurodevelopmental Therapy

SSRN Electronic Journal ◽

10.2139/ssrn.3335873 ◽

2019 ◽

Author(s):

Nicolás Garófalo-Gómez ◽

Jesús Barrera-Reséndiz ◽

María Elena Juárez-Colín ◽

María del Consuelo Pedraza-Aguilar ◽

Cristina Carrillo-Prado ◽

...

Keyword(s):

Brain Injury ◽

Perinatal Brain Injury

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A systematic review on brain injury and altered brain development in moderate-late preterm infants

Early Human Development ◽

10.1016/j.earlhumdev.2020.105094 ◽

2020 ◽

Vol 148 ◽

pp. 105094

Author(s):

Vivian Boswinkel ◽

Jacqueline Nijboer-Oosterveld ◽

Ingrid M. Nijholt ◽

Mireille A. Edens ◽

Susanne M. Mulder - de Tollenaer ◽

...

Keyword(s):

Systematic Review ◽

Brain Injury ◽

Brain Development ◽

Preterm Infants ◽

Late Preterm ◽

Late Preterm Infants

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Perinatal brain injury and regulation of transcription

Current Opinion in Neurology ◽

10.1097/01.wco.0000218229.73678.a8 ◽

2006 ◽

Vol 19 (2) ◽

pp. 141-147 ◽

Cited By ~ 42

Author(s):

Ying-Chao Chang ◽

Chao-Ching Huang

Keyword(s):

Brain Injury ◽

Regulation Of Transcription ◽

Perinatal Brain Injury

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299 PRE-084, A Sigma-1 Receptor Ligand, Protects Against Excitotoxic Perinatal Brain Injury in Newborn Mice

Archives of Disease in Childhood ◽

10.1136/archdischild-2012-302724.0299 ◽

2012 ◽

Vol 97 (Suppl 2) ◽

pp. A87-A88

Author(s):

E. Griesmaier ◽

A. Posod ◽

M. Gross ◽

V. Neubauer ◽

K. Wegleiter ◽

...

Keyword(s):

Brain Injury ◽

Perinatal Brain Injury ◽

Receptor Ligand ◽

Newborn Mice ◽

Sigma 1 Receptor ◽

Sigma 1

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Abstract TP406: Ipsilesional Myelination is Impaired in Children With Perinatal Arterial Stroke

Stroke ◽

10.1161/str.48.suppl_1.tp406 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Sabrina Yu ◽

Helen Carlson ◽

Adam Kirton

Keyword(s):

Brain Injury ◽

Neurological Disorders ◽

Repeated Measures ◽

Population Based ◽

T Test ◽

Biological Processes ◽

Typically Developing ◽

Inclusion Criteria ◽

Perinatal Brain Injury ◽

Perinatal Stroke

Introduction: Stroke is a leading cause of perinatal brain injury and cerebral palsy. Current therapeutic efforts focus on optimizing developmental curves but the biological processes dictating these outcomes are poorly understood. Alterations in myelination are recognized as a major determinant of outcome in preterm brain injury but are unexplored in perinatal stroke (PS). Hypothesis: Ipsilesional delays in myelination occur in children with PS and are associated with poor developmental outcome. Methods: Participants were identified through the Alberta Perinatal Stroke Project, a population-based research cohort. Inclusion criteria were: 1) MRI-confirmed, unilateral arterial PS, 2) T1-weighted MRI >6mo, 3) absence of other neurological disorders, 4) neurological outcome (Pediatric Stroke Outcome Measure, PSOM), and 5) motor assessments (Assisting Hand Assessment, AHA; Melbourne Assessment). FreeSurfer software measured hemispheric asymmetry in myelination intensity. A second method using ImageJ validated the detection of myelination asymmetry. Overall PSOM scores were classified as poor (>1) or not. Repeated measures ANOVA compared perilesional, ipsilesional remote, and contralesional homologous regions. Myelination ratios for stroke cases were compared to typically developing controls (t-test), PSOM scores (t-test), and motor assessments (Pearson’s correlation). Results: Nineteen arterial stroke cases (mean age: 13.73±4.0yo) and 27 controls (mean age: 12.52±3.7yo) were studied. Stroke cases showed a greater degree of asymmetry with lower myelination in the lesioned hemisphere, compared to controls (p<0.001). Myelination in perilesional regions was decreased compared to ipsilesional remote (p<0.001) and contralesional homologous areas (p<0.001). Ipsilesional remote regions were decreased compared to homologous regions on the contralesional hemisphere (p=0.009). Contralesional myelination was also less than controls (p<0.001). Myelination ratios were not associated with PSOM, AHA, or Melbourne scores (p=0.144, 0.218, 0.366 respectively). Conclusion: Myelination of uninjured brain in the lesioned hemisphere is altered in children with PS. Further study is required to determine clinical significance.

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Glial cell responses in a murine multifactorial perinatal brain injury model

Brain Research ◽

10.1016/j.brainres.2017.12.020 ◽

2018 ◽

Vol 1681 ◽

pp. 52-63 ◽

Cited By ~ 5

Author(s):

Miriam Domowicz ◽

Natasha L. Wadlington ◽

Judith G. Henry ◽

Kasandra Diaz ◽

Miranda J. Munoz ◽

...

Keyword(s):

Brain Injury ◽

Glial Cell ◽

Perinatal Brain Injury ◽

Cell Responses ◽

Injury Model

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The Role of Extracellular Vesicles in the Developing Brain: Current Perspective and Promising Source of Biomarkers and Therapy for Perinatal Brain Injury

Frontiers in Neuroscience ◽

10.3389/fnins.2021.744840 ◽

2021 ◽

Vol 15 ◽

Author(s):

Teena K. J. B. Gamage ◽

Mhoyra Fraser

Keyword(s):

Stem Cell ◽

Brain Injury ◽

Extracellular Vesicles ◽

Inflammatory Responses ◽

Brain Structures ◽

Developing Brain ◽

Long Term Effects ◽

Perinatal Brain Injury ◽

Current Perspective ◽

Promising Source

This comprehensive review focuses on our current understanding of the proposed physiological and pathological functions of extracellular vesicles (EVs) in the developing brain. Furthermore, since EVs have attracted great interest as potential novel cell-free therapeutics, we discuss advances in the knowledge of stem cell- and astrocyte-derived EVs in relation to their potential for protection and repair following perinatal brain injury. This review identified 13 peer-reviewed studies evaluating the efficacy of EVs in animal models of perinatal brain injury; 12/13 utilized mesenchymal stem cell-derived EVs (MSC-EVs) and 1/13 utilized astrocyte-derived EVs. Animal model, method of EV isolation and size, route, timing, and dose administered varied between studies. Notwithstanding, EV treatment either improved and/or preserved perinatal brain structures both macroscopically and microscopically. Additionally, EV treatment modulated inflammatory responses and improved brain function. Collectively this suggests EVs can ameliorate, or repair damage associated with perinatal brain injury. These findings warrant further investigation to identify the optimal cell numbers, source, and dosage regimens of EVs, including long-term effects on functional outcomes.

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The Effect of Size and Asymmetry at Birth on Brain Injury and Neurodevelopmental Outcomes in Congenital Heart Disease

Pediatric Cardiology ◽

10.1007/s00246-021-02798-5 ◽

2021 ◽

Author(s):

Shalin A. Parekh ◽

Stephany M. Cox ◽

A. James Barkovich ◽

Vann Chau ◽

Martina A. Steurer ◽

...

Keyword(s):

Brain Injury ◽

Brain Development ◽

Fetal Growth ◽

Infant Development ◽

Growth Parameters ◽

Brain Mri ◽

White Matter Injury ◽

High Risk Infant ◽

Neurodevelopmental Outcomes ◽

Transposition Of Great Arteries

AbstractPoor and asymmetric fetal growth have been associated with neonatal brain injury (BI) and worse neurodevelopmental outcomes (NDO) in the growth-restricted population due to placental insufficiency. We tested the hypothesis that postnatal markers of fetal growth (birthweight (BW), head circumference (HC), and head to body symmetry) are associated with preoperative white matter injury (WMI) and NDO in infants with single ventricle physiology (SVP) and d-transposition of great arteries (TGA). 173 term newborns (106 TGA; 67 SVP) at two sites had pre-operative brain MRI to assess for WMI and measures of microstructural brain development. NDO was assessed at 30 months with the Bayley Scale of Infant Development-II (n = 69). We tested the association between growth parameters at birth with the primary outcome of WMI on the pre-operative brain MRI. Secondary outcomes included measures of NDO. Newborns with TGA were more likely to have growth asymmetry with smaller heads relative to weight while SVP newborns were symmetrically small. There was no association between BW, HC or asymmetry and WMI on preoperative brain MRI or with measures of microstructural brain development. Similarly, growth parameters at birth were not associated with NDO at 30 months. In a multivariable model only cardiac lesion and site were associated with NDO. Unlike other high-risk infant populations, postnatal markers of fetal growth including head to body asymmetry that is common in TGA is not associated with brain injury or NDO. Lesion type appears to play a more important role in NDO in CHD.

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