Discovering hematoma-stimulated circuits for secondary brain injury after intraventricular hemorrhage by spatial transcriptome analysis

Front Immunol. 2023 Feb 7:14:1123652. doi: 10.3389/fimmu.2023.1123652. eCollection 2023.

Abstract

Introduction: Central nervous system (CNS) diseases, such as neurodegenerative disorders and brain diseases caused by acute injuries, are important, yet challenging to study due to disease lesion locations and other complexities.

Methods: Utilizing the powerful method of spatial transcriptome analysis together with novel algorithms we developed for the study, we report here for the first time a 3D trajectory map of gene expression changes in the brain following acute neural injury using a mouse model of intraventricular hemorrhage (IVH). IVH is a common and representative complication after various acute brain injuries with severe mortality and mobility implications.

Results: Our data identified three main 3D global pseudospace-time trajectory bundles that represent the main neural circuits from the lateral ventricle to the hippocampus and primary cortex affected by experimental IVH stimulation. Further analysis indicated a rapid response in the primary cortex, as well as a direct and integrated effect on the hippocampus after IVH stimulation.

Discussion: These results are informative for understanding the pathophysiological changes, including the spatial and temporal patterns of gene expression changes, in IVH patients after acute brain injury, strategizing more effective clinical management regimens, and developing novel bioinformatics strategies for the study of other CNS diseases. The algorithm strategies used in this study are searchable via a web service (www.combio-lezhang.online/3dstivh/home).

Keywords: bioinformatics analysis; intraventricular haemorrhage; neural circuits; secondary brain injury; spatial transcriptome sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain / metabolism
  • Brain Injuries* / genetics
  • Brain Neoplasms*
  • Cerebral Hemorrhage / etiology
  • Gene Expression Profiling
  • Hematoma / etiology
  • Humans

Grants and funding

This work was supported by the State Key Laboratory of Trauma, Burn and Combined Injury (No. SKLYQ202002 to YC), National Key Research and Development Program of China (Nos. 2021YFF1201200 to LZ), National Natural Science Foundation of China (No. 82030036 to HF), Sichuan Science and Technology Program (No. 2022YFS0048 to LZ), and Chongqing Technical Innovation and Application Development Project: Research and Application of Key Technology of Intelligent Risk Control Platform based on Cross-source Multi-dimensional Real-time Technology of Big Data (No.CSTB2022TIAD-KPX0067 to LZ).