Stroke is one of the leading causes of death worldwide. Most stroke survivors remain chronically disabled, and recovery is often difficult as a significant proportion suffer from movement disorders. Stroke recovery continues long after the initial injury has stabilized. During the early recovery period, the first few weeks after injury, the brain enters a prolonged phase of repair and inflammation. This chronic response can have a significant impact on recovery and long-term disability after stroke.
The post-stroke recovery environment plays an important role in the healing process. Recent research suggests that environmental enrichment (EE), a recovery environment that combines more physical activity, sensory stimulation, and social interaction, can improve recovery. However, how stimulation affects brain inflammation and white matter pathology after stroke is not well understood.
To address this, a team of researchers led by Dr. Lluis Kampurby-Ferrer from the Institute of Experimental Neuroinflammation at Lund University in Sweden conducted an animal study to understand the effects of EE on inflammation, microglial responses, and myelin integrity after stroke. The study was made available online on February 25, 2026 and was published in the journal Volume 4, Issue 1. neuroprotection March 1, 2026.
“EE is known to exert beneficial effects on neuroplasticity and recovery after stroke. However, there has been a lack of systematic studies to understand the phenotype of microglia during the post-stroke recovery period in an enriched housing environment. Our study addresses this research gap.” Dr. Campurbi-Ferrer says.
The researchers induced photothrombotic stroke (PT), a commonly used experimental model that causes local damage to the brain, in male mice and then randomized the mice to standard environments (SE) or EE with more space, social contact, opportunities for movement, and frequently exchanged objects. The mice were then monitored for sensorimotor recovery over a three-week period. Additionally, the brains were examined for microglial activity and signs of myelin damage.
Behavioral findings clearly highlighted the role of EE in PT stroke recovery. Mice fed EE performed better on tests of foot placement, foot tomography, and limb symmetry, and the effects persisted for 21 days after stroke. When the researchers combined these results into a composite neurological score, the EE group showed stronger recovery.
Histological analysis revealed that larger infarcts were closely associated with stronger chronic inflammatory signals in SE mice. Additionally, larger lesions result in more myelin debris around the infarct and greater myelin loss in the white matter. In contrast, in EE mice, the usual association between infarct size and chronic inflammatory markers such as galectin-3 was rarely seen. The same was true for myelin debris accumulation and white matter myelin loss. This finding suggests that enrichment reduced the propensity of larger lesions to cause more intense long-term inflammation and tissue destruction.
In the white matter, we found that higher levels of trigger receptors expressed on myeloid cell 2 (TREM2)-positive microglia were associated with better neurological recovery in EE mice. No other inflammatory or myelin markers showed such a strong relationship with behavior. This highlights TREM2-positive microglia as a potential cellular link between EE and improved functional recovery.
“Our findings suggest that interventions such as EE targeting suppression of microglial markers and enhancement of TREM2 may contribute to white matter repair after stroke and improve functional outcomes.” Dr Campurbi-Ferrer concludes:
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Chinese Medical Journal Publishing Co., Ltd.
Reference magazines:
Campurbi-Ferrer, L.et al. (2026). Environmental enrichment modulates inflammation after chronic stroke and is associated with white matter TREM2-positive microglia in mouse recovery. neuroprotection. DOI: 10.1002/nep3.70028. https://onlinelibrary.wiley.com/doi/10.1002/nep3.70028
