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Changes in resting-state functional connectivity after stroke in a mouse brain lacking extracellular matrix

Miriana Jlenia Quattromani1, Jakob Hakon1, Uwe Rauch2

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This study reveals that mice lacking key extracellular matrix (ECM) components show altered brain network activity after stroke. While initially hindering recovery, ECM gene elimination may facilitate later functional plasticity and sensory-motor function restoration.

Keywords:
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Area of Science:

  • Neuroscience
  • Biochemistry
  • Genetics

Background:

  • Focal ischemia (stroke) disrupts brain networks and limits tissue reorganization due to inhibitory extracellular matrix (ECM) molecules.
  • Perineuronal nets (PNNs), formed by ECM components, ensheath inhibitory interneurons and influence sensory processing.
  • Downregulating PNNs promotes neural plasticity and functional recovery post-stroke, but the link to resting-state functional connectivity (RS-FC) is unknown.

Purpose of the Study:

  • To investigate the impact of lacking four key ECM components on neuronal networks and functional recovery after stroke.
  • To examine the relationship between ECM composition, brain functional connectivity, and behavioral outcomes post-stroke.

Main Methods:

  • Utilized a quadruple knock-out (Q4) mouse model lacking brevican, neurocan, tenascin-C, and tenascin-R.
  • Applied functional connectivity optical intrinsic signal (fcOIS) imaging before and after photothrombotic stroke (PT).
  • Assessed limb-placement ability using the paw-placement test at 2, 7, and 14 days post-stroke.

Main Results:

  • Q4 mice displayed significantly impaired homotopic resting-state functional connectivity (RS-FC), particularly in sensory and parietal regions.
  • RS-FC changes correlated with interhemispheric callosal crossings.
  • While infarct size was similar, Q4 mice showed higher early contralesional intrahemispheric RS-FC, potentially facilitating later sensory-motor recovery.

Conclusions:

  • Elimination of specific ECM genes in Q4 mice alters neuronal network function and plasticity post-stroke.
  • Q4 mice offer a valuable model for studying ECM's role in compromising neuronal function and facilitating recovery mechanisms.
  • The findings highlight the complex interplay between ECM, brain networks, and functional recovery after ischemic injury.