TABLE 1.

Enriched environment improves post-stroke neuroplasticity and its underly mechanisms in animal studies.

Ischemia model	Housing condition	Time of intervention	Outcomes	Mechanisms	References
pMCAO	The cage was 65 cm wide, 75 cm long, and 25 cm high, with climbing ladders, plastic tubes and tunnels, running wheels, and small boxes. For environmental novelty, things were changed every 3 days.	Starting after 3 days of pMCAO and lasting for 25 days	The results indicate that an enriched environment positively mitigates the spatial learning and memory deficits caused by permanent middle cerebral artery occlusion.	Enriched environments increase the number of hippocampus synapses and synaptic plasticity by upregulating GAP-43, SYN, and PSD-95.	Wang et al., 2019
tMCAO	Toys, wooden blocks, running wheels, Plexiglas tunnels, ladders, plastic castles, swings, and more were in the 2 m × 2 m × 1 m cage. Rats in an enriched environment spent 10 min in a 120 cm-diameter open field during cage re-decoration. Enriched environment housing and field objects were refreshed daily.	Starting after 3 days of pMCAO and lasting for 14 days	An enriched environment improves spatial learning and memory in MCAO rats.	An enriched environment increased numeric synaptic density in the parietal cortex and induced structural changes in synaptic junctions, decreasing the width of synaptic clefts and increasing the thickness of PSD in the hippocampus and parietal cortex. The enriched environment enhanced the expression of phosphorylated NMDAR1 and PSD-95.	Xu et al., 2009
pMCAO	The cage was a large wooden container (70 cm wide, 85 cm long, and 30 cm tall) with various toys, such as little houses, ladders, tubes, and moving wheels. Every 3 days, these toys were replaced with new forms and colors.	For 21 consecutive days	An enriched environment improves synaptic remodeling and motor function recovery in mice’s ischemic penumbra region after stroke.	Analysis of correlations revealed that the increased expression of GAP-43 and SYN was closely associated with the recovery of limb function in mice with ischemic injury.	Shi et al., 2023
pMCAO	The enriched environment group mice lived in 65 cm wide, 75 cm long, and 25 cm high cages with climbing ladders, exercise wheels, plastic tubes, toys, tunnels, running wheels, sheds, and decorations. To preserve environmental freshness, the circumstances above were changed every 3 day.	For 14 consecutive days	An enriched environment improves locomotion, balance and coordination, and spatial learning memory functions in post-stroke mice.	An enriched environment increases fibronectin type III domain-containing protein 5 (FDNC5) and BDNF expression in the ipsilateral cerebral cortex of mice after stroke.	Yu et al., 2020
tMCAO	The enriched environment cage (86 cm × 76 cm × 24 cm) has running wheels, climbing ladders, nest boxes, hammocks, tunnels, colored balls, and blocks. The lid holds water and a food container like the basic cage. For airflow, the lid has 3 cm openings.	Starting after 5 days of tMCAO and lasting for 21 days	Delayed exposure of cerebral ischemic rats to an enriched environment promotes the survival and density of newborn neurons in the hippocampus and the synaptic density of mature neurons, ultimately improving neurological function and spatial learning deficits.	Histone deacetylase 2 (HDAC2), synaptic-associated proteins, and brain-derived neurotrophic factor (BDNF) may be potential mechanisms for the positive effects of the enriched environment.	Tang et al., 2019
tMCAO	The enriched environment was constructed in a large wire cage (83 × 64 × 56 cm) with several objects (wooden ladders, running wheel, shelter, wooden bridge, wooden and plastic toys, aromatic cotton balls, and hanging chains). Rats reached for food and water through wooden ladders. Eight rats were housed per cage with gentle music and illumination alternating with dark every 2 s. To preserve novelty, these things were rearranged and lowered daily.	For 7 consecutive days	An enriched environment promotes neurogenesis in the subventricular zone after ischemic stroke.	Growth arrest and DNA-damage-inducible protein 45 β (Gadd45b) is associated with subventricular zone (SVZ) neurogenesis after ischemic stroke, and Gadd45b mediates enriched environment-induced SVZ neurogenesis via BDNF.	Tan et al., 2021
tMCAO	A huge plexiglass cage featuring a running wheel, catwalk, play items, and hidden tunnels to facilitate socialization, motor skill development, and other forms of multimodal training.	For 28 consecutive days	An enriched environment improves functional recovery and neurogenesis in aged stroke rats.	The enriched environment promotes neurogenesis by reducing post-stroke inflammation.	Gresita et al., 2022
tMCAO	Task-specific motor rehabilitation is performed by having post-stroke rats grasp sucrose pellets outside their cages for training. The rats are also housed in an enriched environment cage with various toys and novelty items that are changed regularly to promote recovery of synergistic function.	For 14 consecutive days	A rehabilitation program that combines task-specific motor rehabilitation training with an enriched environment can facilitate neurogenesis and functional recovery after a stroke.	Task-specific motor rehabilitation combined with enriched enrichment promotes neural regeneration and maturation of new neuronal dendrites by reversing histone deacetylase 6 (HDAC6) dysfunction caused by cerebral ischemia.	Sheu et al., 2019
tMCAO	Twenty-four hours after MCAO, rats were placed in large cages (50 × 75 × 90 cm) with novel things such as climbing ladders, plastic tunnels, shelters, toys, tubes of varying sizes, and running wheels for free-running.	Starting after 2 days of tMCAO and lasting for 18 days	The enriched environment promoted functional recovery, reduced infarct size, and enhanced angiogenesis.	The enriched environment may promote post-stroke angiogenesis through astrocytic interleukin-17A (IL-17A).	Chen et al., 2023
tMCAO	Ten mice were kept in 100-centimeter-cubic enclosures outfitted with tunnels, hideaways, toys, and running wheels to encourage free-range activity.	For 10 consecutive weeks	An enriched environment promotes functional recovery and angiogenesis in post-stroke mice.	The enriched environment promotes angiogenesis through the PI3K/AKT signaling pathway by promoting astrocyte high-mobility group box-1 (HMGB1) and interleukin-6 (IL-6) expression.	Chen et al., 2017

pMCAO, permanent middle cerebral artery occlusion; tMCAO, transient middle cerebral artery occlusion.