Secondary neurodegeneration or neuroprotection terms don't imply any sense of urgency. The
sounds like an emergency needing immediate intervention. Never use the non-active terminology.
- Funding information
National Health and Medical Research Council (NHMRC) of Australia;
Hunter Medical Research Institute; Faculty of Health and Medicine Pilot
Grant; The University of Newcastle, Australia
Abstract
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 P2Y12 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 P2Y12 to the soma.
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