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Post-Stroke Recovery in Relation to Parvalbumin-Positive Interneurons and Perineuronal Nets.
Lydia M Kuhl1, Matthew S Jeffers2,3,4, Nicolay Hristozov2
1Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, AB, Calgary, Canada.
Neurorehabilitation and Neural Repair
|January 17, 2025
Summary
Stroke recovery is linked to reduced parvalbumin-positive (PV+) interneuron signaling and perineuronal nets (PNNs). This study shows that changes in PV+ interneurons and PNNs correlate with spontaneous behavioral recovery after stroke.
Area of Science:
- Neuroscience
- Neuroplasticity
- Stroke Recovery Research
Background:
- Spontaneous behavioral recovery after stroke occurs during a critical neuroplasticity window.
- This heightened plasticity may be influenced by reduced inhibitory signaling from parvalbumin-positive (PV+) interneurons and the loss of perineuronal nets (PNNs), which stabilize synapses.
Purpose of the Study:
- To investigate the association between behavioral recovery following stroke and changes in the densities of PV+ interneurons and PNNs.
- To elucidate the spatial-temporal profiles of PV+ interneurons and PNNs in the cortex after stroke.
Main Methods:
- Male Sprague-Dawley rats received forelimb motor cortex stroke or vehicle injections.
- Motor function was assessed using behavioral tests.
- Immunofluorescent labeling was used to quantify PNNs (WFA+ cells), PV+ interneurons, and co-labeled cells in ipsilesional and contralesional cortices at various time points post-stroke (days 1, and 1, 2, 4, 6 weeks).
Main Results:
- A significant decrease in PV+ interneuron density was observed at 1-day post-stroke in the lateral ipsilesional cortex.
- PNN density was significantly reduced up to 4 weeks post-stroke in the lateral ipsilesional cortex and at 1-2 weeks in the medial ipsilesional cortex.
- The reduction in combined PV+/PNN signaling correlated with spontaneous behavioral recovery.
Conclusions:
- Post-stroke behavioral recovery is associated with an early reduction in PV+/PNN co-labeled cells.
- This recovery also involves a temporally dependent decrease in PV+ interneuron signaling and a chronic loss of PNNs.
- Targeting PNNs or PV+ interneuron signaling presents potential therapeutic strategies for extending the stroke recovery window.

