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Unveiling the Hidden Impact: Hematoma Volumes Unravel Circuit Disruptions in Intracerebral Hemorrhage

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Abstract

Intracerebral hemorrhage (ICH) imposes a significant burden on patients, and the volume of hematoma plays a crucial role in determining the severity and prognosis of ICH. Although significant recent progress has been made in understanding the cellular and molecular mechanisms of surrounding brain tissue in ICH, our current knowledge regarding the precise impact of hematoma volumes on neural circuit damage remains limited. Here, using a viral tracing technique in a mouse model of striatum ICH, two distinct patterns of injury response were observed in upstream connectivity, characterized by both linear and nonlinear trends in specific brain areas. Notably, even low-volume hematomas had a substantial impact on downstream connectivity. Neurons in the striatum-ICH region exhibited heightened excitability, evidenced by electrophysiological measurements and changes in metabolic markers. Furthermore, a strong linear relationship (R2 = 0.91) was observed between hematoma volumes and NFL damage, suggesting a novel biochemical index for evaluating changes in neural injury. RNA sequencing analysis revealed the activation of the MAPK signaling pathway following hematoma, and the addition of MAPK inhibitor revealed a decrease in neuronal circuit damage, leading to alleviation of motor dysfunction in mice. Taken together, our study highlights the crucial role of hematoma size as a determinant of circuit injury in ICH. These findings have important implications for clinical evaluations and treatment strategies, offering opportunities for precise therapeutic approaches to mitigate the detrimental effects of ICH and improve patient outcomes.

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Data Availability

All data generated in this study are provided in the Supplementary Information and Source Data file. Source data are provided in this paper. The codes supporting the current study have not been deposited in a public repository, but are available from the corresponding author upon request.

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Funding

This work is supported by the National Natural Science Foundation of China 12372303, Venture & Innovation Support Program for Chongqing Overseas Returnees cx2020079, and Scientific and Fundamental Research Funds for the Central Universities (2023CDJXY-050, 2023CDJXY-051).

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Authors and Affiliations

  1. Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, No. 174, Shapingba Main Street, Chongqing, 400030, China

    Yingqing Wu, Ning Hu, Shilei Hao & Bochu Wang

  2. Analytical and Testing Center, Chongqing University, Chongqing, 400030, China

    Qin Deng

  3. The College of Horticulture and Forestry Sciences, Huazhong Agricultural University, Wuhan, 430000, Hubei, China

    Ranran Wei

  4. School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang, 621000, Sichuan, China

    Sen Chen

  5. School of Life Sciences, Anqing Normal University, Anqing, 246052, Anhui, China

    Fusheng Ding

  6. Department of Neurobiology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing, 400030, China

    Haipeng Yu

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  1. Yingqing Wu
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Contributions

Thank the members: S.H. and Y.W. designed the experiments; Y.W. and Q.D. performed the experiments; R.W., S.C., F.D., H.Y., and N.H. performed the data analysis; S.H. and B.W. inspected the data and evaluated the findings; S.H. and B.W. wrote the manuscript with the help from all authors.

Corresponding authors

Correspondence to Shilei Hao or Bochu Wang.

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All animal experiments followed the guidelines set forth by the NIH Guide for the Care and Use of Laboratory Animals (National Academies Press, 2011) and were approved by the Institutional Animal Care and Use Committee of Chongqing University.

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Wu, Y., Deng, Q., Wei, R. et al. Unveiling the Hidden Impact: Hematoma Volumes Unravel Circuit Disruptions in Intracerebral Hemorrhage. Transl. Stroke Res. (2024). https://doi.org/10.1007/s12975-024-01257-6

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