Spatiotemporal analysis of impaired microglia process movement at sites of secondary neurodegeneration post-stroke

Kluge, Murielle G.; Abdolhoseini, Mahmoud; Zalewska, Katarzyna; Ong, Lin Kooi; Johnson, Sarah J.; Nilsson, Michael; Walker, Frederick R.

Title: Spatiotemporal analysis of impaired microglia process movement at sites of secondary neurodegeneration post-stroke
Creator: Kluge, Murielle G.; Abdolhoseini, Mahmoud; Zalewska, Katarzyna; Ong, Lin Kooi; Johnson, Sarah J.; Nilsson, Michael; Walker, Frederick R.
Relation: NHMRC
Relation: Journal of Cerebral Blood Flow & Metabolism Vol. 39, Issue 12, p. 2456-2470
Publisher Link: http://dx.doi.org/10.1177/0271678X18797346
Publisher: Sage
Resource Type: journal article
Date: 2019
Description: It has recently been identified that after motor cortex stroke, the ability of microglia processes to respond to local damage cues is lost from the thalamus, a major site of secondary neurodegeneration (SND). In this study, we combine a photothrombotic stroke model in mice, acute slice and fluorescent imaging to analyse the loss of microglia process responsiveness. The peri-infarct territories and thalamic areas of SND were investigated at time-points 3, 7, 14, 28 and 56 days after stroke. We confirmed the highly specific nature of non-responsive microglia processes to sites of SND. Non-responsiveness was at no time observed at the peri-infarct but started in the thalamus seven days post-stroke and persisted for 56 days. Loss of directed process extension is not a reflection of general functional paralysis as phagocytic function continued to increase over time. Additionally, we identified that somal P₂Y₁₂ was present on non-responsive microglia in the first two weeks after stroke but not at later time points. Finally, both classical microglia activation and loss of process extension are highly correlated with neuronal damage. Our findings highlight the importance of microglia, specifically microglia dynamic functions, to the progression of SND post-stroke, and their potential relevance as modulators or therapeutic targets during stroke recovery.
Subject: microglia motility; live cell multi-photon imaging; laser injury; thalamus; stroke recovery; SDG 3; Sustainable Development Goals
Identifier: http://hdl.handle.net/1959.13/1469790
Identifier: uon:48308
Identifier: ISSN:0271-678X
Language: eng
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