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MicroRNA Regulatory Network as Biomarkers of Late Seizure in Patients with Spontaneous Intracerebral Hemorrhage

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Abstract

Approximately 15% of patients experience seizures after spontaneous intracerebral hemorrhage (ICH). The pathogenesis of seizures post-ICH is not well-known; however, iron deposition–related neuronal injury following hemoglobin breakdown may contribute. Profiling known miRNAs to identify biomarkers for post-ICH late seizures, we found 64 differentially expressed miRNA: 32 upregulated and 32 downregulated in seizure vs. non-seizure. Functional classification of upregulated miRNA for KEGG pathways and biological processes identified enrichment for cell cycle, protein modifications, and FoxO neurotrophin signaling pathways. No significant enrichment was found for downregulated miRNA. Molecular functions Gene Ontology (GO) terms enriched for upregulated miRNA are numerous, while downregulated miRNAs were associated with ion channel activity. RT-PCR confirmed two miRNAs, 4317 and 4325, were differentially expressed in patients who developed seizures at 1 year. MiR-4317 regulates SLC38A1, a glutamine–glutamate transporter. Integrated miRNA–mRNA network analysis identified COMMD6, APOBEC2, and RASSF6—involved in NF-kB regulation. Two miRNAs (miR-4317 and 4325) differentiated post-ICH late seizures vs. non-seizures at 1 year. The results suggest functional and miRNA–mRNA networks as potential biomarkers for post-ICH late seizures.

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Acknowledgments

We thank Lauren Alluli for patient consent and sample preparation.

Funding

Research reported in this publication/presentation is supported by the Ochsner Translational Medicine Research Initiative sponsored by the Ochsner Health System (II) and the Ochsner Clinic Foundation (II and WS).

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Authors and Affiliations

  1. Neurocritical Care and Neurology, University of Queensland, Ochsner Clinical School, Ochsner Medical Center, 1514 Jefferson Highway, New Orleans, LA, 70121, USA

    Ifeanyi Iwuchukwu & Eugene Ramsay

  2. Institute of Translational Research, Ochsner Medical Center, 1514 Jefferson Highway, New Orleans, LA, 70121, USA

    Ifeanyi Iwuchukwu, Doan Nguyen, Michelle Beavers & Vi Tran

  3. Neuroscience Center of Excellence, Louisiana State University Health New Orleans, School of Medicine, 2020 Gravier Street, 8th Floor, New Orleans, LA, 70112, USA

    Ifeanyi Iwuchukwu & Nicolas G. Bazan

  4. Neurosurgery, Ochsner Neuroscience Institute, Ochsner Medical Center, 1514 Jefferson Highway, New Orleans, LA, 70121, USA

    Wale Sulaiman

  5. Department of Neurosurgery, Louisiana State University Health New Orleans, School of Medicine, 2020 Gravier Street, 7th Floor, New Orleans, LA, 70112, USA

    Erin Fannin, Lindsay Lasseigne & Jason Wilson

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  1. Ifeanyi Iwuchukwu
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  2. Doan Nguyen
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Contributions

DN and II conceived the project, designed experiments, analyzed data, and wrote the manuscript. DN, MB, and VT performed all the experiments. MB, EF, LL, and VT performed patient screening and consent, sample processing, clinical data collection, and data analysis. ER, WS, JW, and NB participated in study design and participated in the writing of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Ifeanyi Iwuchukwu.

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Iwuchukwu, I., Nguyen, D., Beavers, M. et al. MicroRNA Regulatory Network as Biomarkers of Late Seizure in Patients with Spontaneous Intracerebral Hemorrhage. Mol Neurobiol 57, 2346–2357 (2020). https://doi.org/10.1007/s12035-020-01872-y

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