A Scoping Review of Preclinical Environmental Enrichment Protocols in Models of Poststroke to Set the Foundations for Translating the Paradigm to Clinical Settings

Translational Stroke Research https://doi.org/10.1007/s12975-025-01335-3 REVIEW A Scoping Review of Preclinical Environmental Enrichment Protocols in Models of Poststroke to Set the Foundations for Translating the Paradigm to Clinical Settings Luca Oppici1 · Guna Bērziņa2,3 · Ann Marie Hestetun‑Mandrup4,5 · Marianne Løvstad4,6 · Arve Opheim4,7 · Matheus M. Pacheco8 · Lena Rafsten7,9 · Katharina S. Sunnerhagen7 · PEER-HOMEcare consortium · James R. Rudd1,10 Received: 04 December 2024 / Revised: 09 January 2025 / Accepted: 26 January 2025 © The Author(s) 2025 Abstract The translation of the highly effective Environmental Enrichment (EE) paradigm from preclinical animal models to human clinical settings has been slow and showed inconsistent results. The primary translational challenge lies in defining what constitutes an EE for humans. To tackle this challenge, this study conducted a scoping review of preclinical EE protocols to explore what constitutes EE for animal models of stroke, laying the foundation for the translation of EE to human application. A systematic search was conducted in the MEDLINE, PsycINFO, and Web of Science databases to identify studies that conducted an EE intervention in the post-stroke animal model. A total of 116 studies were included in the review. A critical reflection of the characteristics of the included studies revealed that EE for post-stroke is a strategy that frequently modifies the animals’ daily environment to create a richness of spatial, structural, and/or social opportunities to engage in a variety of daily life-related motor, cognitive, and social exploratory activities. These activities are relevant to the inhabiting individual and involve the activation of the body function(s) affected by the stroke. This review also identified six principles that underpinned the EE protocols: complexity (spatial and social), variety, novelty, targeting needs, scaffolding, and integration of rehabilitation tasks. These findings can be used as steppingstones to define what constitutes EE in human clinical applications and to develop a set of principles that can inform the design of EE protocols for patients after a stroke. Keywords Enriched environment · Translational · Stroke rehabilitation · Neuroplasticity * Luca Oppici 5 Department of Rehabilitation Science and Health Technology, Oslo Metropolitan University, Oslo, Norway * James R. Rudd 6 Department of Psychology, University of Oslo, Oslo, Norway 7 Institute of Neuroscience and Physiology, Dept of Clinical Neuroscience and Rehabilitation Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden 8 Faculty of Sport, University of Porto, CIFI2D Porto, Portugal 9 Department of Occupational Therapy and Physiotherapy, Sahlgrenska University Hospital, Gothenburg, Sweden 10 Department of Sport, Food and Natural Sciences, Faculty of Education, Arts and Sports, Western Norway University of Applied Sciences, 6856 Sogndal, Norway 1 Department of Teacher Education and Outdoor Studies, Norwegian School of Sport Sciences, 0863 Oslo, Norway 2 Department of Rehabilitation, Faculty of Health and Sport Sciences, Riga Stradiņš University, Riga, Latvia 3 4 Clinic of Rehabilitation, Riga East University Hospital, Riga, Latvia Sunnaas Rehabilitation Hospital, 1450 Nesoddtangen, Norway Vol.:(0123456789) Translational Stroke Research Introduction Environmental Enrichment (EE), also called enriched environment, refers to an experimental paradigm where the living conditions of an individual(s) are modified to increase physical and social stimulation [1]. EE has been shown to provide enhanced motor, cognitive, and sensory stimulation to animals with morbidity [2], and it represents a key paradigm for investigation to enhance poststroke rehabilitation [3]. Evidence indicates that housing animal models of stroke in an EE improves the rehabilitation process through a series of nested mechanisms, such as neurogenesis, increased cortical thickness, and reduction of white matter damage (for a detailed review of the mechanisms, see [3, 4]). These mechanisms underly an enhancement of cognitive and motor functions [5], ultimately leading to an increased autonomy to perform daily functions. The large body of preclinical evidence has generated interest in the clinical community, sparking optimism on the potential of applying principles of EE to improve the rehabilitation after stroke [6, 7]. The translation of the EE paradigm from preclinical to clinical settings however has not yielded the same promise that has been observed in the animal models [8, 9]. The primary translational challenge lies in defining what constitutes an EE for humans [3, 7]. To tackle this challenge, this study conducts a scoping review of preclinical EE protocols to explore what constitutes EE for animal models of stroke, laying the foundation for the translation of EE to human applications. What constitutes EE in animal models of stroke? The initial and most widely used definition of EE is a “combination of social and inanimate stimulation” [1, 10], which was then refined to “housing condition, either home cages or exploratory chambers, that facilitate enhanced sensory, cognitive and motor stimulation” [2] and “enriched environment provides the animals with optimal conditions for enhanced exploration, cognitive activity, social interaction and physical activity” [11]. These definitions converge towards EE being an environment that stimulates enhanced motor, cognitive, and exploratory activities. What constitutes a stimulating environment though has not been systematically scrutinised and defined. To create a stimulating environment, it is common understanding and practice to add elements to an impoverished cage, i.e., a bare cage with a limited number of animals. For instance, studies can increase the size of the cage, or add animal peers, objects, toys, playing objects, or structural layers. What elements are added and how they are added vary across studies. A standardization of the EE protocol could reveal and align perspectives on what constitutes EE. However, this is hardly achievable due to the large variability across experimental conditions, animal genetics, and lab environments [12]. Also, in order to move forward in translating EE models to human conditions, it is theoretically more relevant to understand the key set of principles and approaches that underly the approaches in EE models. This will be useful in guiding individualized human interventions [13]. Researchers have put forward the principles of complexity, variability, and novelty to design EE procedures that can drive physical activity, cognitive activity (e.g., learning), sensory stimulation, and exploratory behaviour [14, 15]. Complexity in the structural and spatial layout of the cage environment [16, 17], novelty and variability in the provision of stimuli to encourage the exploration of novel and alternative solutions and provide a (...truncated)