Arterial specification precedes microvascular restitution in the peri-infarct cortex that is driven by small

Nina Hagemann1,2, Yachao Qi1,2, Ayan Mohamud Yusuf1,2

  • 1Department of Neurology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.

Insights

Stroke causes significant microvascular changes in the brain. Light-sheet microscopy reveals increased collateralization, particularly in small vessels, offering hope for new stroke therapies.

Area of Science:

  • Neuroscience
  • Vascular Biology
  • Medical Imaging

Background:

  • Assessing 3D microvascular networks post-stroke was challenging due to tissue sectioning limitations.
  • Understanding microvascular remodeling is crucial for developing effective stroke treatments.

Purpose of the Study:

  • To investigate long-term microvascular network alterations in the mouse peri-infarct cortex after ischemic stroke.
  • To evaluate the impact of FTY720 (Fingolimod) on microvascular changes post-stroke.
  • To demonstrate the utility of light-sheet microscopy and AI for analyzing microvascular architecture.

Main Methods:

  • Light-sheet microscopy was employed to image the peri-infarct cortex in mice over 56 days post-stroke.
  • Transient middle cerebral artery occlusion (tMCAO) was used to induce ischemic stroke.
  • An AI-based algorithm analyzed microvessel length density, branching points, and expression of α-smooth muscle actin.

Main Results:

  • A transient loss and subsequent reappearance of microvessels were observed in the peri-infarct cortex.
  • Increased microvessel length density and branching points, especially in small vessels, were noted from 7 to 56 days post-stroke.
  • FTY720 administration enhanced the length and branch density of small microvessels.

Conclusions:

  • Stroke induces significant long-term alterations in peri-infarct microvascular architecture, suggesting increased collateralization.
  • Small microvessels play a key role in post-stroke recovery and collateralization.
  • Light-sheet microscopy and AI analysis are powerful tools for assessing microvascular responses to stroke and potential therapies.