Study of the pathology and the underlying molecular mechanism of tissue injury around hematoma following intracerebral hemorrhage

Wang,Jinglei; Chen,Ying; Liang,Jingjing; Cao,Maosheng; Shen,Jiabing; Ke,Kaifu

doi:10.3892/mmr.2021.12341

Study of the pathology and the underlying molecular mechanism of tissue injury around hematoma following intracerebral hemorrhage

Authors:
- Jinglei Wang
- Ying Chen
- Jingjing Liang
- Maosheng Cao
- Jiabing Shen
- Kaifu Ke
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Affiliations: Department of Neurology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
Published online on: August 5, 2021 https://doi.org/10.3892/mmr.2021.12341
Article Number: 702
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Intracerebral hemorrhage (ICH) refers to hemorrhage caused by spontaneous rupture of blood vessels in the brain. Brain injury due to ICH leads to catastrophic effects resulting from the formation of hematoma and oxidative stress caused by components of lysed erythrocytes. However, not all neurons in the area surrounding the hematoma die immediately: A number of neurons remain in a critical, but reversible, state; however, the genes involved in this critical state remain poorly understood. Gene chip technology was used identify changes in the area surrounding the hematoma associated with the upregulation of 210 and downregulation of 173 genes. Gene Ontology functional annotation revealed changes in the gene expression profile in the peripheral region of hematoma following ICH, which were primarily associated with the external stimulation received by the organism, the transmission of harmful information to the cell through the transport of cell membrane proteins, and the regulation of a series of biological processes. Protein interaction network analysis revealed that 11 up‑[secreted phosphoprotein 1, dual specificity phosphatase 9, catechol‑O‑methyltransferase, BAR/IMD domain‑containing adaptor protein 2‑like 1, plakophilin 2, homer scaffold protein 3, ret proto‑oncogene (RET), KIT proto‑oncogene, receptor tyrosine kinase, hepsin, connector enhancer of kinase suppressor of Ras 2 and kalirin RhoGEF kinase] and four downregulated genes (transcription factor AP‑2β, peptidylprolyl isomerase A, SHOC2 leucine rich repeat scaffold protein and synuclein α) may serve a significant role in the area around hematoma following ICH. Reverse transcription‑quantitative PCR was used to verify that these genes were differentially expressed in the ICH compared with the control group. Causal network analysis suggested that the Achaete‑scute homolog 1‑RET signaling axis served a key role in the repair of nerve injury in the peripheral region of hematoma following ICH. Additionally, in vivo experiments revealed that RET expression was upregulated and co‑localized with neurons. Taken together, these results suggested that the changes in the gene expression profile in the area around hematoma following ICH were primarily associated with the repair of damage caused to the nervous system.

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