Structural changes in perineuronal nets and their perforating GABAergic synapses precede motor coordination recovery...

Area of Science:

• Neuroscience
• Extracellular Matrix Biology
• Stroke Research

Background:

• Stroke causes significant long-term disability, with limited restorative therapies due to poor understanding of brain recovery.
• The brain's extracellular matrix (ECM), particularly perineuronal nets (PNNs) around interneurons, is implicated in neuroplasticity.
• This study investigates PNN contributions to recovery after focal cerebral ischemia in mice.

Purpose of the Study:

• To explore the role of perineuronal nets (PNNs) in neurological recovery following focal cerebral ischemia.
• To understand how PNN structural changes influence neuronal function and brain plasticity post-stroke.
• To investigate the interaction between PNNs, synapses, and immune cells in stroke recovery.

Main Methods:

• Utilized 3D superresolution microscopy (STED, SR-SIM) to analyze PNN structural remodeling after stroke.
• Employed graph theory for topological analysis of PNN morphology.
• Quantified PNN-associated synapses and microglia/macrophage contacts using confocal microscopy following transient middle cerebral artery occlusion (tMCAO).

Main Results:

• Stroke induced transient PNN structural changes, enabling reorganization of GABAergic input to motor cortex interneurons.
• Coordinated remodeling of PNNs and inhibitory synapses preceded motor function recovery, dependent on injury severity.
• PNN alterations correlated with increased contact between activated microglia/macrophages and PNN-associated neurons.

Conclusions:

• Identified a novel post-stroke neuroplasticity mechanism involving PNNs, synapses, and microglia/macrophages.
• PNN loosening in the post-acute phase may extend the therapeutic window for neuroplasticity into the chronic stroke phase.
• Targeting PNNs offers a potential strategy for enhancing stroke recovery.