Brain Res Bull. 2020 Dec;165:169-177. doi: 10.1016/j.brainresbull.2020.09.023. Epub 2020 Oct 11.

Heterogeneous nuclear ribonucleoprotein A1 exerts protective role in intracerebral hemorrhage-induced secondary brain injury in rats

Weiye Zhu  1 Jiasheng Ding  1 Liang Sun  1 Jiang Wu  1 Xiang Xu  1 Wenjie Wang  1 Haiying Li  1 Haitao Shen  1 Xiang Li  2 Zhengquan Yu  3 Gang Chen  1

  • 1 Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, Jiangsu Province, China.
  • 2 Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, Jiangsu Province, China. Electronic address: xiangli2017@suda.edu.cn.
  • 3 Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, Jiangsu Province, China. Electronic address: zhengquan_yu@126.com.

Abstract

Heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) is the most abundant and expressed widely member of the hnRNP family. It has been extensively studied in developmental biology, oncology, and neurodegenerative diseases, which has not been reported on in intracerebral hemorrhage (ICH) induced-secondary brain injury (SBI). The purpose of this study was to explore the role of hnRNPA1 exerts and its underlying mechanism in ICH-induced SBI. Experimental ICH models were established by injecting autologous heart blood into the basal ganglia region of rats and increased or inhibited hnRNPA1 expression through the hnRNPA1 plasmid and small interfering RNA. The results illustrated that the protein levels of hnRNPA1 are significantly elevated after ICH, and hnRNPA1 is transported from the nucleus to the cytoplasm. Upregulated hnRNPA1 could improve neurological function and the learning and memory ability decline after ICH-induced injury. Furthermore, TUNEL and FJB staining indicated that hnRNPA1 overexpression could reduce neuronal cell death and injury induced by ICH. However, downregulated hnRNPA1 damages neurological function and learning and memory abilities and aggravates neuronal cell degeneration and apoptosis. Consistently, the levels of Bcl-xl mRNA and Bcl-xl are elevated or decreased depending on the levels of hnRNPA1, which could be one of the mechanisms through which hnRNPA1 participates in ICH-induced neuronal cell death. In summary, hnRNPA1 plays a protective role in ICH-induced SBI via upregulating Bcl-xl expression, indicating that hnRNPA1 could be a potential target for ICH therapy.

Keywords: BCL-xl; Hemorrhage; HnRNPA1; Intracerebral; Neuronal apoptosis; Secondary brain injury.

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