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The Effect of the Relationship of APOE Polymorphisms and Cerebral Vasospasm on Functional Outcomes in Children With Traumatic Brain Injury.

ABSTRACT: BACKGROUND:Pediatric traumatic brain injury (TBI) is a leading cause of death and disability. Polymorphisms in the apolipoprotein E ( APOE) gene have been linked to cerebral vasospasm (CV) and poor outcomes in adults with TBI, yet these associations remain poorly defined in children. OBJECTIVE:We examined the effect of the relationship between APOE polymorphisms and CV on functional outcomes in children with a TBI. METHOD:This prospective, descriptive study examined 60 children (aged 10 days to 15 years) with a TBI. Data included demographic information, genetic sampling for the APOE gene and single-nucleotide polymorphisms (SNPs; rs405509, rs429358, rs7412), and daily transcranial Doppler ultrasounds to evaluate for CV. We examined Glasgow Outcome Scale-Extended Pediatrics (GOS-E Peds) scores at the time of discharge and 4-6 weeks after discharge. RESULTS:More than half (56.7%) of the 60 children ( Mage = 5.9 years) were male. Twenty-six participants (43.3%) experienced an occurrence of CV. There were significant differences in injury mechanism (unadjusted p = .048) and age (unadjusted p = .02) between those with and without CV. Also, the noncoding promoter SNP rs405509 T/T, when considered with injury severity, appeared to modify the relationship of APOE genotype to CV. The relationship between APOE and CV had no significant effect on GOS-E Peds scores. CONCLUSION:Injury severity and the APOE noncoding promoter SNP rs405509 may modify the relationship between APOE and CV in children with TBI. More studies are needed to understand the role of APOE polymorphisms in outcomes in children with TBI.

SUBMITTER: Reuter-Rice K

PROVIDER: S-EPMC6346318 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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The Effect of the Relationship of APOE Polymorphisms and Cerebral Vasospasm on Functional Outcomes in Children With Traumatic Brain Injury.

Reuter-Rice Karin K Regier Michael M Bennett Ellen E Laskowitz Daniel D

Biological research for nursing 20180711 5

<h4>Background</h4>Pediatric traumatic brain injury (TBI) is a leading cause of death and disability. Polymorphisms in the apolipoprotein E ( APOE) gene have been linked to cerebral vasospasm (CV) and poor outcomes in adults with TBI, yet these associations remain poorly defined in children.<h4>Objective</h4>We examined the effect of the relationship between APOE polymorphisms and CV on functional outcomes in children with a TBI.<h4>Method</h4>This prospective, descriptive study examined 60 chil ...[more]

PMID: 29996665

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Project description:BackgroundTraumatic brain injury (TBI) initiates a complex sequence of destructive and neuroprotective cellular responses. The initial mechanical injury is followed by an extended time period of secondary brain damage. Due to the complicated pathological picture a better understanding of the molecular events occurring during this secondary phase of injury is needed. This study was aimed at analysing gene expression patterns following cerebral cortical contusion in rat using high throughput microarray technology with the goal of identifying genes involved in an early and in a more delayed phase of trauma, as genomic responses behind secondary mechanisms likely are time-dependent.ResultsAmong the upregulated genes 1 day post injury, were transcription factors and genes involved in metabolism, e.g. STAT-3, C/EBP-delta and cytochrome p450. At 4 days post injury we observed increased gene expression of inflammatory factors, proteases and their inhibitors, like cathepsins, alpha-2-macroglobulin and C1q. Notably, genes with biological function clustered to immune response were significantly upregulated 4 days after injury, which was not found following 1 day. Osteopontin and one of its receptors, CD-44, were both upregulated showing a local mRNA- and immunoreactivity pattern in and around the injury site. Fewer genes had decreased expression both 1 and 4 days post injury and included genes implicated in transport, metabolism, signalling, and extra cellular matrix formation, e.g. vitronectin, neuroserpin and angiotensinogen.ConclusionThe different patterns of gene expression, with little overlap in genes, 1 and 4 days post injury showed time dependence in genomic responses to trauma. An early induction of factors involved in transcription could lead to the later inflammatory response with strongly upregulated CD-44 and osteopontin expression. An increased knowledge of genes regulating the pathological mechanisms in trauma will help to find future treatment targets. Since trauma is a risk factor for development of neurodegenerative disease, this knowledge may also reduce late negative effects.

Dataset Information

The Effect of the Relationship of APOE Polymorphisms and Cerebral Vasospasm on Functional Outcomes in Children With Traumatic Brain Injury.

Publications

The Effect of the Relationship of APOE Polymorphisms and Cerebral Vasospasm on Functional Outcomes in Children With Traumatic Brain Injury.

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