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MicroRNA Profile Differences in Neonates at Risk for Cerebral Palsy.

ABSTRACT: Background:MicroRNAs; miRs are used as biomarkers in the diagnosis of several diseases. Cerebral palsy; CP, resulting from perinatal brain injury, cannot be diagnosed until 18-24 months old. Biomarkers to predict CP and assess response to investigational therapies are needed. We hypothesized that miRs expressed in neonates with the CP risk factors of abnormal tone and/or intraventricular hemorrhage; IVH differ from those without risk factors. Methods:This was a cohort study of neonates at risk for CP. Subjects <32 weeks gestation and <1500 grams were recruited from neonatal intensive care units at a large urban delivery hospital and an adjacent children's hospital. Thirty-one plasma samples were evaluated. An unbiased examination was performed by locked nucleic acid quantitative real time - polymerase chain reaction; qRT-PCR. Results were evaluated in the context of IVH and abnormal tone. Results:Plasma miR profiles in neonates at risk for CP differ when comparing those with and without IVH, and with and without abnormal tone. Restricted profiles were found in each condition with greater differences in the tone comparison than the IVH comparison. Conclusion:Plasma miR profiles show potential in predicting CP. This study also suggests biologically plausible candidates for future studies.

SUBMITTER: Chapman SD

PROVIDER: S-EPMC6364989 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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MicroRNA Profile Differences in Neonates at Risk for Cerebral Palsy.

Chapman S D SD Farina L L Kronforst K K Dizon Mlv M

Physical medicine and rehabilitation international 20180531 3

<h4>Background</h4>MicroRNAs; miRs are used as biomarkers in the diagnosis of several diseases. Cerebral palsy; CP, resulting from perinatal brain injury, cannot be diagnosed until 18-24 months old. Biomarkers to predict CP and assess response to investigational therapies are needed. We hypothesized that miRs expressed in neonates with the CP risk factors of abnormal tone and/or intraventricular hemorrhage; IVH differ from those without risk factors.<h4>Methods</h4>This was a cohort study of neo ...[more]

PMID: 30740584

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Project description:Cerebral palsy (CP) is an upper motor neuron disease that results in a progressive movement disorder. Secondary to the neurological insult, muscles from CP patients often become spastic. Spastic muscle is characterized by an increased resistance to stretch, but often develops the further complication of contracture which represents a prominent disability in children with CP. This study's purpose is to characterize alterations of spastic muscle on the transcriptional level. Increased knowledge of spastic muscle may lead to novel therapies to improve the quality of life for children with CP.The transcriptional profile of spastic muscles were defined in children with cerebral palsy and compared to control patients using Affymetrix U133A chips. Expression data were verified using quantitative-PCR (QPCR) and validated with SDS-PAGE for select genes. Significant genes were determined using a 2 x 2 ANOVA and results required congruence between 3 preprocessing algorithms.CP patients clustered independently and 205 genes were significantly altered, covering a range of cellular processes. Placing gene expression in the context of physiological pathways, the results demonstrated that spastic muscle in CP adapts transcriptionally by altering extracellular matrix, fiber type, and myogenic potential. Extracellular matrix adaptations occur primarily in the basal lamina although there is increase in fibrillar collagen components. Fiber type is predominately fast compared to normal muscle as evidenced by contractile gene isoforms and decrease in oxidative metabolic gene transcription, despite a paradoxical increased transcription of slow fiber pathway genes. We also found competing pathways of fiber hypertrophy with an increase in the anabolic IGF1 gene in parallel with a paradoxical increase in myostatin, a gene responsible for stopping muscle growth. We found evidence that excitation-contraction coupling genes are altered in muscles from patients with CP and may be a significant component of disease.This is the first transcriptional profile performed on spastic muscle of CP patients and these adaptations were not characteristic of those observed in other disease states such as Duchenne muscular dystrophy and immobilization-induced muscle atrophy. Further research is required to understand the mechanism of muscle adaptation to this upper motor neuron lesion that could lead to the development of innovative therapies.

Project description:ImportanceCerebral palsy (CP) is considered a pediatric condition despite most individuals with CP living into adulthood. Thus, there is a lack of evidence in adults with CP, which includes a paucity of research examining mental health in this population.ObjectivesTo determine the risk of depression and anxiety in adults with CP compared with an age-, sex-, and practice-matched reference group of adults without CP, using primary care data.Design, setting, and participantsRetrospective longitudinal cohort study set in UK primary care. Data were analyzed using Cox proportional hazards regression analyses adjusted for chronic conditions and visits to their physician. The study period ran from January 1987 to November 2015. Data of entry into the study ranged from January 1987 to September 2015. Data for 1705 adults 18 years or older with CP and 5115 matched adults without CP were extracted. Cerebral palsy was identified using diagnostic codes, and each person with CP was compared with 3 age-, sex-, and practice-matched controls.ExposuresDiagnosis of CP, with a second analysis accounting for comorbidity of intellectual disability (ID).Main outcomes and measuresTime to diagnosis for depression or anxiety following the date of entry into the study in adults with CP (with and without ID) compared with matched controls.ResultsThe mean (SD) age of the 1705 patients with CP and the 5115 adults without CP was 33.3 (15.5) years, and 798 participants (46.8%) were women. Individuals with CP had an increased adjusted hazard of depression (hazard ratio [HR], 1.28; 95% CI, 1.09-1.51) and anxiety (HR, 1.40; 95% CI, 1.21-1.63) compared with the matched reference group. When we accounted for ID comorbidity, there were 363 adults with CP who also had ID (mean [SD] age, 32.1 [13.2] years; 159 women [47.6%]) and 1342 adults with CP who did not have ID (mean [SD] age, 33.6 [16.1] years; 639 women [43.8%]). Only those individuals with CP and no comorbid ID had a higher risk of incident depression (HR, 1.44; 95% CI, 1.20-1.72) and anxiety (HR, 1.55; 95% CI, 1.28-1.87) than their matched controls.Conclusions and relevanceAdults with CP have an increased risk of depression or anxiety. In particular, these results indicate that this association is driven largely by those individuals with CP with no co-occurring ID. Future work is needed in community-based samples to fully elucidate the causal mechanisms driving these associations.

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MicroRNA Profile Differences in Neonates at Risk for Cerebral Palsy.

Publications

MicroRNA Profile Differences in Neonates at Risk for Cerebral Palsy.

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