Connecting chloride transporter impairment following perinatal brain injury to cerebral palsy

2020 ◽  
pp. 405-430
Author(s):  
Jessie C. Newville ◽  
Akosua Y. Oppong ◽  
Shenandoah Robinson ◽  
Lauren L. Jantzie
Keyword(s):  
Cerebral Palsy ◽  
Brain Injury ◽  
Perinatal Brain Injury

scholarly journals Sustained peripheral immune hyper-reactivity (SPIHR): an enduring biomarker of altered inflammatory responses in adult rats after perinatal brain injury

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Yuma Kitase ◽  
Eric M. Chin ◽  
Sindhu Ramachandra ◽  
Christopher Burkhardt ◽  
Nethra K. Madurai ◽  
...  
Keyword(s):  
Cerebral Palsy ◽  
Brain Injury ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Serum Levels ◽  
In Utero ◽  
Cell Populations ◽  
Perinatal Brain Injury ◽  
Chemokine Ligand ◽  
Immune Changes

Abstract Background Chorioamnionitis (CHORIO) is a principal risk factor for preterm birth and is the most common pathological abnormality found in the placentae of preterm infants. CHORIO has a multitude of effects on the maternal–placental–fetal axis including profound inflammation. Cumulatively, these changes trigger injury in the developing immune and central nervous systems, thereby increasing susceptibility to chronic sequelae later in life. Despite this and reports of neural–immune changes in children with cerebral palsy, the extent and chronicity of the peripheral immune and neuroinflammatory changes secondary to CHORIO has not been fully characterized. Methods We examined the persistence and time course of peripheral immune hyper-reactivity in an established and translational model of perinatal brain injury (PBI) secondary to CHORIO. Pregnant Sprague–Dawley rats underwent laparotomy on embryonic day 18 (E18, preterm equivalent). Uterine arteries were occluded for 60 min, followed by intra-amniotic injection of lipopolysaccharide (LPS). Serum and peripheral blood mononuclear cells (PBMCs) were collected at young adult (postnatal day P60) and middle-aged equivalents (P120). Serum and PBMCs secretome chemokines and cytokines were assayed using multiplex electrochemiluminescent immunoassay. Multiparameter flow cytometry was performed to interrogate immune cell populations. Results Serum levels of interleukin-1β (IL-1β), IL-5, IL-6, C–X–C Motif Chemokine Ligand 1 (CXCL1), tumor necrosis factor-α (TNF-α), and C–C motif chemokine ligand 2/monocyte chemoattractant protein-1 (CCL2/MCP-1) were significantly higher in CHORIO animals compared to sham controls at P60. Notably, CHORIO PBMCs were primed. Specifically, they were hyper-reactive and secreted more inflammatory mediators both at baseline and when stimulated in vitro. While serum levels of cytokines normalized by P120, PBMCs remained primed, and hyper-reactive with a robust pro-inflammatory secretome concomitant with a persistent change in multiple T cell populations in CHORIO animals. Conclusions The data indicate that an in utero inflammatory insult leads to neural–immune changes that persist through adulthood, thereby conferring vulnerability to brain and immune system injury throughout the lifespan. This unique molecular and cellular immune signature including sustained peripheral immune hyper-reactivity (SPIHR) and immune cell priming may be a viable biomarker of altered inflammatory responses following in utero insults and advances our understanding of the neuroinflammatory cascade that leads to perinatal brain injury and later neurodevelopmental disorders, including cerebral palsy.

scholarly journals Neonatal Functional and Structural Connectivity Are Associated with Cerebral Palsy at Two Years of Age

2019 ◽  
Vol 37 (02) ◽  
pp. 137-145
Author(s):  
Stephanie L. Merhar ◽  
Elveda Gozdas ◽  
Jean A. Tkach ◽  
Nehal A. Parikh ◽  
Beth M. Kline-Fath ◽  
...  
Keyword(s):  
Cerebral Palsy ◽  
Brain Injury ◽  
Functional Connectivity ◽  
Diffusion Tensor ◽  
Structural Connectivity ◽  
Motor Task ◽  
Structural Mri ◽  
Perinatal Brain Injury ◽  
The Right ◽  
Almost All

Objective The accuracy of structural magnetic resonance imaging (MRI) to predict later cerebral palsy (CP) in newborns with perinatal brain injury is variable. Diffusion tensor imaging (DTI) and task-based functional MRI (fMRI) show promise as predictive tools. We hypothesized that infants who later developed CP would have reduced structural and functional connectivity as compared with those without CP. Study Design We performed DTI and fMRI using a passive motor task at 40 to 48 weeks' postmenstrual age in 12 infants with perinatal brain injury. CP was diagnosed at age 2 using a standardized examination. Results Five infants had CP at 2 years of age, and seven did not have CP. Tract-based spatial statistics showed a widespread reduction of fractional anisotropy (FA) in almost all white matter tracts in the CP group. Using the median FA value in the corticospinal tracts as a cutoff, FA was 100% sensitive and 86% specific to predict CP compared with a sensitivity of 60 to 80% and a specificity of 71% for structural MRI. During fMRI, the CP group had reduced functional connectivity from the right supplemental motor area as compared with the non-CP group. Conclusion DTI and fMRI obtained soon after birth are potential biomarkers to predict CP in newborns with perinatal brain injury.

Congenital Anomalies in Children With Cerebral Palsy: A Systematic Review

2019 ◽  
Vol 34 (12) ◽  
pp. 720-727 ◽  
Author(s):  
Shona Goldsmith ◽  
Sarah McIntyre ◽  
Michele Hansen ◽  
Nadia Badawi
Keyword(s):  
Systematic Review ◽  
Cerebral Palsy ◽  
Brain Injury ◽  
Congenital Anomalies ◽  
Circulatory System ◽  
Population Based ◽  
Included Study ◽  
Quality Data ◽  
Study Cohort ◽  
Perinatal Brain Injury

Congenital anomalies are a strong risk factor for cerebral palsy, particularly for children born at term. This systematic review aimed to address gaps in our understanding of the association between congenital anomalies and cerebral palsy. Eight population-based studies (n = 10 081) were identified. Congenital anomalies were reported in 12% to 32% of children with pre/perinatal brain injury and 20% of children with postneonatal brain injury. Variation between studies included study cohort inclusion criteria and the definitions and classification of included anomalies. The most common cerebral anomalies were microcephaly and hydrocephaly, whereas circulatory system anomalies were the most common noncerebral anomalies. The proportion of congenital anomalies was higher in children born at term than preterm. Synthesizing the highest quality data published, this review identified that congenital anomalies are common in cerebral palsy. New collaborative research, addressing sources of variation, is vital to identify pathways to cerebral palsy that include specific congenital anomalies, and explore opportunities for prevention.

Inhibition of return in children with perinatal brain injury

2001 ◽  
Vol 7 (3) ◽  
pp. 275-284 ◽  
Author(s):  
JEFFREY SCHATZ ◽  
SUZANNE CRAFT ◽  
DESIREE WHITE ◽  
T.S. PARK ◽  
GARY S. FIGIEL
Keyword(s):  
Cerebral Palsy ◽  
Brain Injury ◽  
Magnetic Resonance ◽  
Visual Attention ◽  
Inhibition Of Return ◽  
Perinatal Brain Injury ◽  
Neurologic Injury ◽  
Short Delay ◽  
Perinatal Injury ◽  
Attention System

Inhibition of return is a bias in attention that reduces the likelihood of returning attention to previously viewed locations. This attention bias develops during the first 6 months of life and is putatively mediated by midbrain structures. The present study evaluated the effects of perinatal lesions on the development of inhibition of return. Thirty-three children with perinatal injury resulting in spastic diplegic cerebral palsy were grouped based on magnetic resonance exams. Children with anterior (n = 5), posterior (n = 12), diffuse (n = 8), or no apparent (n = 8) lesions were compared with a group of age-matched children without neurologic injury (n = 39) on an orienting task designed to elicit inhibition of return. Short-delay trials demonstrated grossly intact facilitation of attention for all groups. Long-delay trials that produced inhibition of return in the control and posterior injury groups indicated a disruption of inhibition of return in the groups with anterior and diffuse lesions. The findings are consistent with previous reports that anterior regions are important for the developing attention system, and that bilateral injury can result in unilateral disruption of visual attention. (JINS, 2001, 7, 275–284.)

LOCOMOTION IS IMPACTED DIFFERENTLY ACCORDING TO THE PERINATAL BRAIN INJURY MODEL: META-ANALYSIS OF PRECLINICAL STUDIES WITH IMPLICATIONS FOR CEREBRAL PALSY

2021 ◽  
pp. 109250
Author(s):  
Sabrina da Conceição Pereira ◽  
Raul Manhães-de-Castro ◽  
Diego Bulcão Visco ◽  
Glayciele Leandro de Albuquerque ◽  
Caio Matheus Santos da Silva Calado ◽  
...  
Keyword(s):  
Cerebral Palsy ◽  
Brain Injury ◽  
Meta Analysis ◽  
Preclinical Studies ◽  
Perinatal Brain Injury ◽  
Injury Model

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

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

scholarly journals Virtual Reality in Neurorehabilitation: An Umbrella Review of Meta-Analyses

2021 ◽  
Vol 10 (7) ◽  
pp. 1478
Author(s):  
Alexandra Voinescu ◽  
Jie Sui ◽  
Danaë Stanton Fraser
Keyword(s):  
Virtual Reality ◽  
Cerebral Palsy ◽  
Brain Injury ◽  
Upper Limb ◽  
Umbrella Review ◽  
High Quality ◽  
Quality Of Evidence ◽  
Upper Limb Function ◽  
Meta Analyses

Neurological disorders are a leading cause of death and disability worldwide. Can virtual reality (VR) based intervention, a novel technology-driven change of paradigm in rehabilitation, reduce impairments, activity limitations, and participation restrictions? This question is directly addressed here for the first time using an umbrella review that assessed the effectiveness and quality of evidence of VR interventions in the physical and cognitive rehabilitation of patients with stroke, traumatic brain injury and cerebral palsy, identified factors that can enhance rehabilitation outcomes and addressed safety concerns. Forty-one meta-analyses were included. The data synthesis found mostly low- or very low-quality evidence that supports the effectiveness of VR interventions. Only a limited number of comparisons were rated as having moderate and high quality of evidence, but overall, results highlight potential benefits of VR for improving the ambulation function of children with cerebral palsy, mobility, balance, upper limb function, and body structure/function and activity of people with stroke, and upper limb function of people with acquired brain injury. Customization of VR systems is one important factor linked with improved outcomes. Most studies do not address safety concerns, as only nine reviews reported adverse effects. The results provide critical recommendations for the design and implementation of future VR programs, trials and systematic reviews, including the need for high quality randomized controlled trials to test principles and mechanisms, in primary studies and in meta-analyses, in order to formulate evidence-based guidelines for designing VR-based rehabilitation interventions.

scholarly journals Comparison of motor outcomes between preschool children with univentricular and biventricular critical heart disease not diagnosed with cerebral palsy or acquired brain injury

2021 ◽  
pp. 1-8
Author(s):  
M. Florencia Ricci ◽  
Alastair Fung ◽  
Diane Moddemann ◽  
Victoria Micek ◽  
Gwen Y. Bond ◽  
...  
Keyword(s):  
Cerebral Palsy ◽  
Heart Disease ◽  
Preschool Children ◽  
Brain Injury ◽  
Standard Deviation ◽  
Motor Skills ◽  
Odds Ratio ◽  
Motor Impairment ◽  
Acquired Brain Injury ◽  
Manual Dexterity

Abstract This comparison study of two groups within an inception cohort aimed to compare the frequency of motor impairment between preschool children with univentricular and biventricular critical congenital heart disease (CHD) not diagnosed with cerebral palsy/acquired brain injury, describe and compare their motor profiles and explore predictors of motor impairment in each group. Children with an intellectual quotient <70 or cerebral palsy/acquired brain injury were excluded. Motor skills were assessed with the Movement Assessment Battery for Children-2. Total scores <5th percentile indicated motor impairment. Statistical analysis included χ2 test and multiple logistic regression analysis. At a mean age of 55.4 (standard deviation 3.77) months, motor impairment was present in 11.8% of those with biventricular critical CHD, and 32.4% (p < 0.001) of those with univentricular critical CHD. The greatest difference between children with biventricular and univentricular CHD was seen in total test scores 8.73(2.9) versus 6.44(2.8) (p < 0.01) and in balance skills, 8.84 (2.8) versus 6.97 (2.5) (p = 0.001). Manual dexterity mean scores of children with univentricular CHD were significantly below the general population mean (>than one standard deviation). Independent odds ratio for motor impairment in children with biventricular critical CHD was presence of chromosomal abnormality, odds ratio 10.9 (CI 2.13–55.8) (p = 0.004); and in children with univentricular critical CHD odds ratio were: postoperative day 1–5 highest lactate (mmol/L), OR: 1.65 (C1.04–2.62) (p = 0.034), and dialysis requirement any time before the 4.5-year-old assessment, OR: 7.8 (CI 1.08–56.5) (p = 0.042). Early assessment of motor skills, particularly balance and manual dexterity, allows for intervention and supports that can address challenges during the school years.

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