Dataset Information

Potential biomarkers for neuroinflammation and neurodegeneration at short and long term after neonatal hypoxic-ischemic insult in rat.

ABSTRACT:

Background

Hypoxic-ischemic (HI) encephalopathy causes life-long morbidity and premature mortality in term neonates. Therapies in addition to whole-body cooling are under development to treat the neonate at risk for HI encephalopathy, but are not a quickly measured serum inflammatory or neuronal biomarkers to rapidly and accurately identify brain injury in order to follow the efficacy of therapies.

Methods

In order to identify potential biomarkers for early inflammatory and neurodegenerative events after neonatal hypoxia-ischemia, both male and female Wistar rat pups at postnatal day 7 (P7) were used and had their right carotid artery permanently doubly occluded and exposed to 8% oxygen for 90?min. Sensory and cognitive parameters were assessed by open field, rotarod, CatWalk, and Morris water maze (MWM) test. Plasma and CSF biomarkers were investigated on the acute (24?h and 72?h) and chronic phase (4 weeks). Brains were assessed for gene expression analysis by quantitative RT-PCR Array.

Results

We found a delay of neurological reflex maturation in HI rats. We observed anxiolytic-like baseline behavior in males more than females following HI injury. HI rats held on the rotarod for a shorter time comparing to sham. HI injury impaired spatial learning ability on MWM test. The CatWalk assessment demonstrated a long-term deficit in gait parameters related to the hind paw. Proinflammatory biomarkers such as IL-6 in plasma and CCL2 and TNF-? in CSF showed an upregulation at 24?h after HI while other cytokines, such as IL-17A and CCL5, were upregulated after 72?h in CSF. At 24?h post-injury, we observed an increase of Edn1, Hif1-?, and Mmp9 mRNA levels in the ipsilateral vs the contralateral hemisphere of HI rats. An upregulation of genes involved with clotting and hematopoietic processes was observed 72?h post-injury.

Conclusions

Our work showed that, in the immature brain, the HI injury induced an early increased production of several proinflammatory mediators detectable in plasma and CSF, followed by tissue damage in the hypoxic hemisphere and short-term as well as long-lasting neurobehavioral deficits.

SUBMITTER: Borjini N

PROVIDER: S-EPMC6819609 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Potential biomarkers for neuroinflammation and neurodegeneration at short and long term after neonatal hypoxic-ischemic insult in rat.

Borjini Nozha N Sivilia Sandra S Giuliani Alessandro A Fernandez Mercedes M Giardino Luciana L Facchinetti Fabrizio F Calzà Laura L

Journal of neuroinflammation 20191028 1

<h4>Background</h4>Hypoxic-ischemic (HI) encephalopathy causes life-long morbidity and premature mortality in term neonates. Therapies in addition to whole-body cooling are under development to treat the neonate at risk for HI encephalopathy, but are not a quickly measured serum inflammatory or neuronal biomarkers to rapidly and accurately identify brain injury in order to follow the efficacy of therapies.<h4>Methods</h4>In order to identify potential biomarkers for early inflammatory and neurod ...[more]

PMID: 31660990

Similar Datasets

Project description:Hypoxic-ischemic encephalopathy (HIE) is the most common cause of neonatal acquired brain injury. Although conventional MRI may predict neurodevelopmental outcomes, accurate prognostication remains difficult. As diffusion tensor imaging (DTI) may provide an additional diagnostic and prognostic value over conventional MRI, we aimed to develop a composite DTI (cDTI) score to relate to short-term neurological function. Sixty prospective neonates treated with therapeutic hypothermia (TH) for HIE were evaluated with DTI, with a voxel size of 1 × 1 × 2 mm. Fractional anisotropy (FA) and mean diffusivity (MD) from 100 neuroanatomical regions (FA/MD *100 = 200 DTI parameters in total) were quantified using an atlas-based image parcellation technique. A least absolute shrinkage and selection operator (LASSO) regression was applied to the DTI parameters to generate the cDTI score. Time to full oral nutrition [short-term oral feeding (STO) score] was used as a measure of short-term neurological function and was correlated with extracted DTI features. Seventeen DTI parameters were selected with LASSO and built into the final unbiased regression model. The selected factors included FA or MD values of the limbic structures, the corticospinal tract, and the frontotemporal cortices. While the cDTI score strongly correlated with the STO score (rho = 0.83, p = 2.8 × 10-16), it only weakly correlated with the Sarnat score (rho = 0.27, p = 0.035) and moderately with the NICHD-NRN neuroimaging score (rho = 0.43, p = 6.6 × 10-04). In contrast to the cDTI score, the NICHD-NRN score only moderately correlated with the STO score (rho = 0.37, p = 0.0037). Using a mixed-model analysis, interleukin-10 at admission to the NICU (p = 1.5 × 10-13) and tau protein at the end of TH/rewarming (p = 0.036) and after rewarming (p = 0.0015) were significantly associated with higher cDTI scores, suggesting that high cDTI scores were related to the intensity of the early inflammatory response and the severity of neuronal impairment after TH. In conclusion, a data-driven unbiased approach was applied to identify anatomical structures associated with some aspects of neurological function of HIE neonates after cooling and to build a cDTI score, which was correlated with the severity of short-term neurological functions.

Dataset Information

Potential biomarkers for neuroinflammation and neurodegeneration at short and long term after neonatal hypoxic-ischemic insult in rat.

Background

Methods

Results

Conclusions

Publications

Potential biomarkers for neuroinflammation and neurodegeneration at short and long term after neonatal hypoxic-ischemic insult in rat.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets