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Characterising Microglial Immunoreactivity In The Mouse Brain Post-Stroke: Impacts Of Environmental Enrichment

Kolbay, Ömer Kaan (2025) MOBM02 20251
Degree Projects in Molecular Biology
Abstract
Stroke remains a leading cause of long-term disability worldwide, making effective recovery critical for minimizing residual impairments. Given the limited scope of pharmacological interventions in the post-stroke recovery phase, effective non-pharmacological strategies are essential for supporting better prognosis. One experimental approach to enhancing recovery in rodent models is environmental enrichment, a paradigm that combines multisensory stimulation with increased voluntary physical activity. So far, enriched environments have been shown to support neuroplasticity and improve behavioral outcomes following various neurological conditions, including stroke. However, the extent to which the enrichment influences the neuroinflammatory... (More)
Stroke remains a leading cause of long-term disability worldwide, making effective recovery critical for minimizing residual impairments. Given the limited scope of pharmacological interventions in the post-stroke recovery phase, effective non-pharmacological strategies are essential for supporting better prognosis. One experimental approach to enhancing recovery in rodent models is environmental enrichment, a paradigm that combines multisensory stimulation with increased voluntary physical activity. So far, enriched environments have been shown to support neuroplasticity and improve behavioral outcomes following various neurological conditions, including stroke. However, the extent to which the enrichment influences the neuroinflammatory response at the tissue remains insufficiently understood. In this work, we investigated how enrichment may affect microglial dynamics and the broader inflammatory characteristics following stroke, based on a variety of indicators for inflammation. Using brain tissues of mice with a photothrombotic stroke model, we explored the inflammatory state across two groups: animals housed under enriched conditions and those housed in standard conditions during a 21-day post-stroke recovery period. Immunofluorescence staining was used to quantify microglial markers, including those associated with homeostasis (P2RY12), pro-inflammatory microglial activation (Galectin-3), phagocytosis (CD68 and BODIPY dye), and tissue repair (TREM-2), alongside myelin staining to assess structural integrity in both groups. Our findings suggest that mice in the enriched group exhibited signs of a more regulated and balanced inflammatory profile shown through the observed trends in the expression of Galectin-3+ microglia, and an overall increase in CD68+ expression, indicating enhanced phagocytic activity. Additional differences in marker expression were noted, as well as in the extent of myelin preservation and recovery. The noted differences underscore the relevance of the recovery context in shaping neuroimmune responses and lay more groundwork for future research aimed at investigating environment-based interventions for stroke rehabilitation. (Less)
Popular Abstract
Exploring The Effects Of Environment In The Recovering Brain

Stroke remains a major global health burden, ranking as the second-leading cause of death and a leading cause of long-term disability. Recent global estimates report over 12 million new stroke cases annually, with over 100 million stroke survivors, some of which are living with lasting physical, sensory, or cognitive impairments. In addition to its impact on mortality and disability, stroke imposes a massive economic burden, with financial strains on healthcare worldwide. Despite the extensive experience accumulated in our understanding of stroke as a neurological condition, the treatment options remain limited and difficult to address. Conversely, lifestyle interventions are... (More)
Exploring The Effects Of Environment In The Recovering Brain

Stroke remains a major global health burden, ranking as the second-leading cause of death and a leading cause of long-term disability. Recent global estimates report over 12 million new stroke cases annually, with over 100 million stroke survivors, some of which are living with lasting physical, sensory, or cognitive impairments. In addition to its impact on mortality and disability, stroke imposes a massive economic burden, with financial strains on healthcare worldwide. Despite the extensive experience accumulated in our understanding of stroke as a neurological condition, the treatment options remain limited and difficult to address. Conversely, lifestyle interventions are valuable in the recovery stages, as they are known to improve the motor deficits experienced.

In this study, we explored how living in an enriched environment -in which there are possibilities for more physical activity, sensory stimulation, and social interaction- might influence brain recovery after stroke in mice. To examine this, we used mice tissue with stroke that were previously taken after a 3-week recovery period and compared two groups: mice recovering in standard housing, and another group recovering in enriched housing, designed to promote movement and engagement. In these tissues, we wanted to look closely at microglia, the brain’s immune cells, which play a central role in both damage and repair.

Through fluorescent labeling of the tissues, we tracked several types of cellular activity that can be associated with microglia. We found that mice living in the enriched environment showed a more balanced response in the brain. Specifically, they had fewer signs for an increase in harmful inflammation, which was apparent in tissues with more significant stroke damage, and they showed more activity related to tissue cleanup and repair, which can be seen as a potential link to better preservation of the brain structure and function.

These results suggest that for stroke, the environment in which the recovery takes place matters: a richer, more stimulating environmental setting can help shape how the brain heals after injury. While our results do not conclusively show major changes in healing, they support the idea that non-medical factors like daily surroundings could play a real role in stroke rehabilitation.

Master’s Degree Project in Molecular Biology / 30 Hp / 2025
Supervisors: Tomas Deierborg
Neuroinflammation / Department of Experimental Medical Science (Less)
Please use this url to cite or link to this publication:
author
Kolbay, Ömer Kaan
supervisor
organization
course
MOBM02 20251
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
9214512
date added to LUP
2025-10-24 15:42:53
date last changed
2025-10-24 15:42:53
@misc{9214512,
  abstract     = {{Stroke remains a leading cause of long-term disability worldwide, making effective recovery critical for minimizing residual impairments. Given the limited scope of pharmacological interventions in the post-stroke recovery phase, effective non-pharmacological strategies are essential for supporting better prognosis. One experimental approach to enhancing recovery in rodent models is environmental enrichment, a paradigm that combines multisensory stimulation with increased voluntary physical activity. So far, enriched environments have been shown to support neuroplasticity and improve behavioral outcomes following various neurological conditions, including stroke. However, the extent to which the enrichment influences the neuroinflammatory response at the tissue remains insufficiently understood. In this work, we investigated how enrichment may affect microglial dynamics and the broader inflammatory characteristics following stroke, based on a variety of indicators for inflammation. Using brain tissues of mice with a photothrombotic stroke model, we explored the inflammatory state across two groups: animals housed under enriched conditions and those housed in standard conditions during a 21-day post-stroke recovery period. Immunofluorescence staining was used to quantify microglial markers, including those associated with homeostasis (P2RY12), pro-inflammatory microglial activation (Galectin-3), phagocytosis (CD68 and BODIPY dye), and tissue repair (TREM-2), alongside myelin staining to assess structural integrity in both groups. Our findings suggest that mice in the enriched group exhibited signs of a more regulated and balanced inflammatory profile shown through the observed trends in the expression of Galectin-3+ microglia, and an overall increase in CD68+ expression, indicating enhanced phagocytic activity. Additional differences in marker expression were noted, as well as in the extent of myelin preservation and recovery. The noted differences underscore the relevance of the recovery context in shaping neuroimmune responses and lay more groundwork for future research aimed at investigating environment-based interventions for stroke rehabilitation.}},
  author       = {{Kolbay, Ömer Kaan}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{Characterising Microglial Immunoreactivity In The Mouse Brain Post-Stroke: Impacts Of Environmental Enrichment}},
  year         = {{2025}},
}