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Long Noncoding RNA GAS5-Involved Progression of Neonatal Hydrocephalus and Inflammatory Responses

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Abstract

Intraventricular hemorrhage results in posthemorrhagic hydrocephalus (PHH). Neonatal hydrocephalus remains a challenging disease due to the high failure rate of all management strategies. We evaluated long noncoding RNA growth arrest-specific 5 (GAS5)-mediated network in neonatal hydrocephalus, providing a new direction for the treatment of hydrocephalus. The PHH model was constructed in neonatal rats after intracerebroventricular injection with GAS5, miR-325-3p, and chaperonin containing T-complex protein 1, subunit 8 (CCT8) plasmids, or oligonucleotides. Next, behavioral tests, measurement of serum inflammation, observation of brain tissue pathology, and calculation of hemoglobin and brain water contents were implemented. GAS5, miR-325-3p, and CCT8 expression, in combination with their interactions, was checked. As the results reported, collagenase infusion induced hydrocephalus, impairing neurological function, enhancing inflammation and neuronal apoptosis, and increasing hemoglobin and brain water contents. GAS5 and CCT8 were up-regulated, while miR-325-3p was down-regulated in hydrocephalic rats. Downregulating GAS5/CCT8 or upregulating miR-325-3p could inhibit inflammatory response and improve neurological function in young hydrocephalic rats. GAS5 promotes CCT8 expression through sponge adsorption of miR-325-3p. GAS5 silencing-mediated protections against hydrocephalus were counteracted by CCT8 overexpression. In summary, GAS5 aggravates neonatal hydrocephalus and inflammatory responses in a way of leasing miR-325-3p-involved regulation of CCT8.

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The data and materials used to support the findings of this study are available from the corresponding author.

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Acknowledgements

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Funding

National Natural Science Foundation of China (NO. (2019) 13, 81971217).

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  1. Bin Zou and Qin Zhang have contributed equally to this work.

Authors and Affiliations

  1. Department of Neurosurgery, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, No. 20, Jinyu Avenue, Yubei District, Chongqing City, 401122, China

    Bin Zou, Yudong Zhou, Xuan Zhai & Ping Liang

  2. Department of Cardiology, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing City, 401122, China

    Qin Zhang

  3. Chongqing Medical University, Chongqing City, 400016, China

    Hui Gan & Yue Qin

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Correspondence to Ping Liang.

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All animal experiments were complied with the ARRIVE guidelines and performed in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals. The experiments were approved by the Institutional Animal Care and Use Committee of Chongqing Medical University (Approval Number: 201706-AC59311).

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Zou, B., Zhang, Q., Gan, H. et al. Long Noncoding RNA GAS5-Involved Progression of Neonatal Hydrocephalus and Inflammatory Responses. Mol Biotechnol (2024). https://doi.org/10.1007/s12033-024-01077-x

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