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

Murielle G Kluge1,2, Mahmoud Abdolhoseini3, Katarzyna Zalewska1,2

  • 1School of Biomedical Sciences and Pharmacy and the Priority Research Centre for Stroke and Brain Injury, University of Newcastle, Callaghan, NSW, Australia.

Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism
|September 12, 2018
PubMed

Insights

After stroke, microglia in the thalamus lose their ability to respond to damage, contributing to secondary neurodegeneration. This loss of microglia process responsiveness persists long-term and correlates with neuronal damage.

Area of Science:

  • Neuroscience
  • Immunology
  • Stroke Research

Background:

  • Stroke can lead to secondary neurodegeneration (SND) in connected brain regions like the thalamus.
  • Microglia, the brain's immune cells, are crucial for responding to injury.
  • Previous studies suggest impaired microglia function in stroke-affected areas.

Purpose of the Study:

  • To investigate the dynamic changes in microglia process responsiveness following a motor cortex stroke.
  • To determine the temporal and spatial characteristics of microglia non-responsiveness in secondary neurodegeneration sites.
  • To explore the relationship between microglia function, neuronal damage, and stroke recovery.

Main Methods:

  • Utilized a photothrombotic stroke model in mice.
  • Employed acute slice preparation and fluorescent imaging techniques.
  • Analyzed microglia behavior at multiple time points (3, 7, 14, 28, 56 days post-stroke) in peri-infarct and thalamic regions.

Main Results:

  • Microglia process responsiveness was specifically lost in thalamic areas of SND, not the peri-infarct zone.
  • This non-responsiveness began seven days post-stroke and lasted for 56 days.
  • Phagocytic function remained high, and P2Y12 expression varied, indicating specific functional deficits rather than general paralysis.
  • Loss of process extension and classical microglia activation strongly correlated with neuronal damage.

Conclusions:

  • Microglia dynamic functions are critical in the progression of secondary neurodegeneration after stroke.
  • Impaired microglia responsiveness in the thalamus contributes significantly to stroke-induced neuronal damage.
  • Targeting microglia dynamic functions may offer therapeutic potential for stroke recovery.
Keywords:
Microglia motilitylaser injurylive cell multi-photon imagingstroke recoverythalamus

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