2. Academic Validation
  3. Cerebrovascular vulnerability and fibrosis in human brain aneurysms

Cerebrovascular vulnerability and fibrosis in human brain aneurysms

  • Nat Neurosci. 2026 Jun 10. doi: 10.1038/s41593-026-02326-9.
Jerry C Wang # 1,  Chang N Kim # 1 2 3 4,  Shubhang Bhalla 1,  Lea Scherschinski 5 6,  Adnan Gopinadhan 1,  Santhosh Arul 1,  Damian Sanchez 1,  Tyler D Schriber 5 6,  Amanda C M Apolonio 7 8,  Belda Gülsuyu 1,  Muhammet M Öztürk 1,  John P Andrews 1,  Joseph Kim 1,  Behnam Rezai Jahromi 9,  Mika Niemelä 9,  Martin Lehecka 9,  Aunoy Poddar 1,  Thomas Wälchli 10 11,  Joshua S Catapano 5 6,  Rajeev D Sen 12,  Michael R Levitt 12,  Daniel L Cooke 13,  Kazim Narsinh 13,  Ruchira M Jha 14,  Tomoki Hashimoto 5 6,  S Paul Oh 5 6,  Eric J Huang 15,  Edward F Chang 1,  Daniel A Lim 1 2,  Adib A Abla 1,  Andrew C Yang 7 8,  Tomasz J Nowakowski 1 2 3 4,  Michael T Lawton 16 17,  Ethan A Winkler 18
Affiliations

Affiliations

  • 1 Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
  • 2 Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA, USA.
  • 3 Department of Anatomy, University of California, San Francisco, San Francisco, CA, USA.
  • 4 Department of Psychiatry, University of California, San Francisco, San Francisco, CA, USA.
  • 5 Department of Neurosurgery, Barrow Neurological Institute & St Joseph's Hospital and Medical Center, Phoenix, AZ, USA.
  • 6 Barrow Aneurysm and AVM Research Center, Department of Translational Neuroscience, Barrow Neurological Institute, St Joseph's Hospital and Medical Center, Phoenix, AZ, USA.
  • 7 Gladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA, USA.
  • 8 Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
  • 9 Department of Neurosurgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
  • 10 Brain Vasculature and Perivascular Niche Laboratory, Department of Oncology, University College London Cancer Institute, University College London, London, UK.
  • 11 Victor Horsley Department of Neurosurgery, National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Trust, Queen Square, London, UK.
  • 12 Departments of Neurological Surgery, Radiology, Neurology, Mechanical Engineering, and Stroke & Applied Neuroscience Center, University of Washington, Seattle, WA, USA.
  • 13 Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, USA.
  • 14 Department of Neurology, Barrow Neurological Institute & St Joseph's Hospital and Medical Center, Phoenix, AZ, USA.
  • 15 Department of Pathology, University of California, San Francisco, San Francisco, CA, USA.
  • 16 Department of Neurosurgery, Barrow Neurological Institute & St Joseph's Hospital and Medical Center, Phoenix, AZ, USA. [email protected].
  • 17 Barrow Aneurysm and AVM Research Center, Department of Translational Neuroscience, Barrow Neurological Institute, St Joseph's Hospital and Medical Center, Phoenix, AZ, USA. [email protected].
  • 18 Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA. [email protected].
  • # Contributed equally.
PMID: 42271045 DOI: 10.1038/s41593-026-02326-9
Abstract

Brain aneurysms are a cerebrovascular disease that results in a severe type of stroke. The cell-specific molecular pathology underlying their formation and rupture is unknown. Here we profile 227,663 neurovascular cells, including 52,946 aneurysmal cells, from a total of 14 adult human brain aneurysms and 11 control vessels. Our atlas of human brain aneurysms, as well as cell-resolution spatial transcriptomics, revealed that pathological cerebrovascular remodeling occurs with the loss of structurally supportive smooth muscle cells and the emergence of activated perivascular fibroblasts, which re-populate the vascular wall and express multiple genes linked to aneurysm risk. Fibrotic changes coincide with fibroblast-myeloid cell signaling pathways and an influx of specialized macrophages that are rarely detected in non-aneurysmal cerebrovasculature and that express destabilizing vascular cell programs. Thus, we reveal an unrecognized interplay between cerebrovascular fibrosis and myeloid inflammation during disease progression, substantially advancing our understanding of the cellular drivers and mechanisms underlying this devastating cerebrovascular disease that will inform translational development.

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