- Title
- Impaired microglia process dynamics post-stroke are specific to sites of secondary neurodegeneration
- Creator
- Kluge, Murielle G.; Kracht, Laura; Abdolhoseini, Mahmoud; Ong, Lin Kooi; Johnson, Sarah J.; Nilsson, Michael; Walker, Frederick R.
- Relation
- GLIA Vol. 65, Issue 12, p. 1885-1899
- Publisher Link
- http://dx.doi.org/10.1002/glia.23201
- Publisher
- John Wiley & Sons
- Resource Type
- journal article
- Date
- 2017
- Description
- Stroke induces tissue death both at the site of infarction and at secondary sites connected to the primary infarction. This latter process has been referred to as secondary neurodegeneration (SND). Using predominantly fixed tissue analyses, microglia have been implicated in regulating the initial response at both damage sites post-stroke. In this study, we used acute slice based multiphoton imaging, to investigate microglia dynamic process movement in mice 14 days after a photothrombotic stroke. We evaluated the baseline motility and process responses to locally induced laser damage in both the peri-infarct (PI) territory and the ipsilateral thalamus, a major site of post-stroke SND. Our findings show that microglia process extension toward laser damage within the thalamus is lost, yet remains robustly intact within the PI territory. However, microglia at both sites displayed an activated morphology and elevated levels of commonly used activation markers (CD68, CD11b), indicating that the standardly used fixed tissue metrics of microglial "activity" are not necessarily predictive of microglia function. Analysis of the purinergic P₂ Y₁₂ receptor, a key regulator of microglia process extension, revealed an increased somal localization on nonresponsive microglia in the thalamus. To our knowledge, this is the first study to identify a non-responsive microglia phenotype specific to areas of SND post-stroke, which cannot be identified by the classical assessment of microglia activation but rather the localization of P₂ Y₁₂ to the soma.
- Subject
- laser injury; live cell multiphoton imaging; P₂Y₁₂ receptor; peri-infarct; thalamus
- Identifier
- http://hdl.handle.net/1959.13/1390613
- Identifier
- uon:33097
- Identifier
- ISSN:0894-1491
- Language
- eng
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