2. Academic Validation
  3. Clearance of intracranial debris by ultrasound reduces inflammation and improves outcomes in hemorrhagic stroke models

Clearance of intracranial debris by ultrasound reduces inflammation and improves outcomes in hemorrhagic stroke models

  • Nat Biotechnol. 2025 Nov 10. doi: 10.1038/s41587-025-02866-8.
Matine M Azadian 1 2 3,  Sepideh Kiani Shabestari 2,  Arjun Rajan 4 5,  Payton J Martinez 1,  Nicholas Macedo 1,  Eric Markarian 1,  Yun Xiang 1,  Brenda J Yu 1 6,  Paul M George 2,  Ryann M Fame 4,  Raag D Airan 7 8 9
Affiliations

Affiliations

  • 1 Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.
  • 2 Department of Neurology, Stanford University School of Medicine, Stanford, CA, USA.
  • 3 Neurosciences Graduate Program, Stanford University School of Medicine, Stanford, CA, USA.
  • 4 Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA.
  • 5 Developmental Biology Graduate Program, Stanford University School of Medicine, Stanford, CA, USA.
  • 6 Biophysics Graduate Program, Stanford University School of Medicine, Stanford, CA, USA.
  • 7 Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA. [email protected].
  • 8 Department of Materials Science and Engineering, Stanford University School of Medicine, Stanford, CA, USA. [email protected].
  • 9 Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA. [email protected].
PMID: 41214344 DOI: 10.1038/s41587-025-02866-8
Abstract

Impaired clearance of neurotoxic debris in the brain exacerbates neurologic disease and presents a promising therapeutic target. Pharmacologic therapies can enhance meningeal lymphatic clearance in preclinical models but may be limited by systemic toxicities or invasive administration. Here we report a low-intensity, focused ultrasound protocol that noninvasively clears pathogenic substances from the cerebrospinal fluid and brain interstitium in mice. Using two models of hemorrhagic stroke, we demonstrate that this protocol clears the cerebrospinal fluid and interstitium of blood cells, which accumulate in the deep cervical lymph nodes via meningeal lymphatics. The protocol directly modulates molecular processes, including mechanosensitive channels, to shift microglial phenotypes and astrocytic Aquaporin localization to reduce neuroinflammation and neurocytotoxicity. In the intracerebral hemorrhage model, it improves behavioral outcomes and increases survival with greater efficacy than a pharmacologic benchmark. The protocol satisfies Food and Drug Administration safety guidelines, supporting clinical translatability. If demonstrated effective clinically, it may provide therapeutic benefit not only in hemorrhagic stroke but also in Other neurologic disorders that involve impaired debris clearance.

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