Proteomics - Clinical Applications
Proteomics - Clinical Applications
5 years ago

Upregulation of inflammatory mediators in the ventricular zone after cortical stroke

Leigh Anne Swayne, Adrianna N. Gunton, Juan C. Sanchez-Arias, Leigh E. Wicki-Stordeur, Esther O. Carmona-Wagner
Purpose After cortical stroke, neural precursor cells (NPCs) in the distal ventricular zone (VZ) proliferate more rapidly and migrate toward the injured cortex. While evidence suggests this can enhance stroke recovery, the underlying molecular mechanisms initiating the response are poorly understood. Here we identified changes in protein expression in the ipsilateral VZ early (4 h) after stroke to gain insight into the initial mechanisms involved in NPC activation post-stroke. Experimental design Four hours after photothrombotic stroke (or sham surgery control) in the sensorimotor cortex, adult mice (10 stroke, 10 sham) were subjected to cardiac perfusion with PBS, and ipsilateral and contralateral VZ tissue was microdissected. Two separate sets of ipsilateral and contralateral VZ tissues (from 5 pooled surgery or 5 pooled sham mice) were analyzed simultaneously using 8-plex iTRAQ. We used Western blotting and confocal microscopy to confirm changes in protein expression in the VZ ipsilateral to stroke in a separate cohort of mice. Results We identified nine proteins which exhibited a significant mean increase (by ≥ 2-fold) in stroke ipsilateral compared to sham ipsilateral. Many of these proteins were antiproteases or cytokine/growth factor binding proteins that are known to act as inflammatory responders or effectors and play roles in modulating tissue growth and remodeling. Conclusion and clinical relevance These novel findings support a growing body of literature that inflammatory signaling is involved in the NPC response to brain injury and identifies novel potential targets that could be exploited to better understand and to optimize this regenerative response.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/prca.201600092

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