2. Academic Validation
  3. Unveiling the Hidden Impact: Hematoma Volumes Unravel Circuit Disruptions in Intracerebral Hemorrhage

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

  • Transl Stroke Res. 2024 May 15. doi: 10.1007/s12975-024-01257-6.
Yingqing Wu 1,  Qin Deng 2,  Ranran Wei 3,  Sen Chen 4,  Fusheng Ding 5,  Haipeng Yu 6,  Ning Hu 1,  Shilei Hao 7,  Bochu Wang 8
Affiliations

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.
  • 2 Analytical and Testing Center, Chongqing University, Chongqing, 400030, China.
  • 3 The College of Horticulture and Forestry Sciences, Huazhong Agricultural University, Wuhan, 430000, Hubei, China.
  • 4 School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang, 621000, Sichuan, China.
  • 5 School of Life Sciences, Anqing Normal University, Anqing, 246052, Anhui, China.
  • 6 Department of Neurobiology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing, 400030, China.
  • 7 Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, No. 174, Shapingba Main Street, Chongqing, 400030, China. shilei_hao@cqu.edu.cn.
  • 8 Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, No. 174, Shapingba Main Street, Chongqing, 400030, China. wangbc2000@126.com.
PMID: 38748378 DOI: 10.1007/s12975-024-01257-6
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.

Keywords

Brain-wide connectivity; Hematoma volumes; MAPK signaling pathway; Neurofilament light chain; Neuronal excitability.

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