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Environmental Enrichment in Stroke Research: an Update

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Abstract

Environmental enrichment (EE) refers to different forms of stimulation, where the environment is designed to improve the levels of sensory, cognitive, and motor stimuli, inducing stroke recovery in animal models. Stroke is a leading cause of mortality and neurological disability among older adults, hence the importance of developing strategies to improve recovery for such patients. This review provides an update on recent findings, compiling information regarding the parameters affected by EE exposure in both preclinical and clinical studies. During stroke recovery, EE exposure has been shown to improve both the cognitive and locomotor aspects, inducing important neuroplastic alterations, increased angiogenesis and neurogenesis, and modified gene expression, among other effects. There is a need for further research in this field, particularly in those aspects where the evidence is inconclusive. Moreover, it is necessary refine and adapt the EE paradigms for application in human patients.

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References

  1. WHO WHO. Stroke, Cerebrovascular accident [Internet]. http://www.emro.who.int/health-topics/stroke-cerebrovascular-accident/index.html#:~:text=Stroke%20carries%20a%20high%20risk,way%20it%20strikes%20people%20down. 2022. Available from: http://www.emro.who.int/health-topics/stroke-cerebrovascular-accident/index.html#:~:text=Stroke

  2. Hannan AJ. Review: Environmental enrichment and brain repair: harnessing the therapeutic effects of cognitive stimulation and physical activity to enhance experience-dependent plasticity. Neuropathol Appl Neurobiol. 2014;40:13–25.

    Article  CAS  PubMed  Google Scholar 

  3. Mcdonald MW, Hayward KS, Rosbergen ICM, Jeffers MS, Corbett D. Is environmental enrichment ready for clinical application in human post-stroke rehabilitation ? Front Behav Neurosci. 2018;12:1–16.

    Article  Google Scholar 

  4. Hebb D. The effects of early experience on problem solving at maturity. Am Psychol. 1947;2:306–7.

    Google Scholar 

  5. Nithianantharajah J, Hannan AJ. Enriched environments, experience-dependent plasticity and disorders of the nervous system. Nat Rev Neurosci. 2006;7:697–709.

    Article  CAS  PubMed  Google Scholar 

  6. Rosenzweig MR, Bennett EL. Psychobiology of plasticity: effects of training and experience on brain and behavior. Behav Brain Res Netherlands. 1996;78:57–65.

    Article  CAS  Google Scholar 

  7. Smail MA, Smith BL, Nawreen N, Herman JP. Differential impact of stress and environmental enrichment on corticolimbic circuits. Pharmacol Biochem Behav [Internet]. Elsevier; 2020;197:172993. Available from: https://doi.org/10.1016/j.pbb.2020.172993

  8. Bennett EL, Rosenzweig MR, Diamond MC. Rat brain: effects of environmental enrichment on wet and dry weights. Sci U S. 1969;163:825–6.

    CAS  ADS  Google Scholar 

  9. Diamond MC, Krech D, Rosenzweig MR. The effects of an enriched environment on the histology of the rat cerebral cortex. J Comp Neurol [Internet]. 1964;123:111–9. https://doi.org/10.1002/cne.901230110. (John Wiley & Sons, Ltd Available from).

    Article  CAS  PubMed  Google Scholar 

  10. Leggio MG, Mandolesi L, Federico F, Spirito F, Ricci B, Gelfo F, et al. Environmental enrichment promotes improved spatial abilities and enhanced dendritic growth in the rat. Behav Brain Res. 2005;163:78–90.

    Article  PubMed  Google Scholar 

  11. Connor JR, Wang EC, Diamond MC. Increased length of terminal dendritic segments in old adult rats’ somatosensory cortex: an environmentally induced response. Exp Neurol [Internet]. 1982;78:466–70. Available from: https://www.sciencedirect.com/science/article/pii/0014488682900644

  12. Kempermann G, Kuhn HG, Gage FH. More hippocampal neurons in adult mice living in an enriched environment. Nature [Internet]. 1997;386:493–5. https://doi.org/10.1038/386493a0. (Available from).

    Article  CAS  PubMed  ADS  Google Scholar 

  13. Gogolla N, Galimberti I, Deguchi Y, Caroni P. Wnt signaling mediates experience-related regulation of synapse numbers and mossy fiber connectivities in the adult hippocampus. Neuron [Internet]. 2009;62:510–25. Available from: https://www.sciencedirect.com/science/article/pii/S0896627309003468

  14. Turner AM, Greenough WT. Differential rearing effects on rat visual cortex synapses I Synaptic and neuronal density and synapses per neuron. Brain Res Netherlands. 1985;329:195–203.

    Article  CAS  Google Scholar 

  15. Greenough WT, Hwang HMF, Gorman C. Evidence for active synapse formation or altered postsynaptic metabolism in visual cortex of rats reared in complex environments. Proc Natl Acad Sci U S A. 1985;82:4549–52.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  16. Jones TA, Greenough WT. Ultrastructural evidence for increased contact between astrocytes and synapses in rats reared in a complex environment. Neurobiol Learn Mem [Internet]. 1996;65:48–56. Available from: https://www.sciencedirect.com/science/article/pii/S1074742796900052

  17. Ickes BR, Pham TM, Sanders LA, Albeck DS, Mohammed AH, Granholm A-C. Long-term environmental enrichment leads to regional increases in neurotrophin levels in rat brain. Exp Neurol [Internet]. 2000;164:45–52. Available from: https://www.sciencedirect.com/science/article/pii/S0014488600974156

  18. Torasdotter M, Metsis M, Henriksson BG, Winblad B, Mohammed AH. Environmental enrichment results in higher levels of nerve growth factor mRNA in the rat visual cortex and hippocampus. Behav Brain Res Netherlands. 1998;93:83–90.

    Article  CAS  Google Scholar 

  19. Frick KM, Fernandez SM. Enrichment enhances spatial memory and increases synaptophysin levels in aged female mice. Neurobiol Aging United States. 2003;24:615–26.

    Article  CAS  Google Scholar 

  20. Nithianantharajah J, Levis H, Murphy M. Environmental enrichment results in cortical and subcortical changes in levels of synaptophysin and PSD-95 proteins. Neurobiol Learn Mem United States. 2004;81:200–10.

    Article  CAS  Google Scholar 

  21. Tang Y-P, Wang H, Feng R, Kyin M, Tsien JZ. Differential effects of enrichment on learning and memory function in NR2B transgenic mice. Neuropharmacology [Internet]. 2001;41:779–90. Available from: https://www.sciencedirect.com/science/article/pii/S0028390801001228

  22. Naka F, Narita N, Okado N, Narita M. Modification of AMPA receptor properties following environmental enrichment. Brain Dev Netherlands. 2005;27:275–8.

    Article  Google Scholar 

  23. Rampon C, Jiang CH, Dong H, Tang YP, Lockhart DJ, Schultz PG, et al. Effects of environmental enrichment on gene expression in the brain. Proc Natl Acad Sci U S A. 2000;97:12880–4.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  24. Rampon C, Tang YP, Goodhouse J, Shimizu E, Kyin M, Tsien JZ. Enrichment induces structural changes and recovery from nonspatial memory deficits in CA1 NMDAR1-knockout mice. Nat Neurosci United States. 2000;3:238–44.

    Article  CAS  Google Scholar 

  25. Schrijver NCA, Bahr NI, Weiss IC, Würbel H. Dissociable effects of isolation rearing and environmental enrichment on exploration, spatial learning and HPA activity in adult rats. Pharmacol Biochem Behav United States. 2002;73:209–24.

    Article  CAS  Google Scholar 

  26. Bennett JC, McRae PA, Levy LJ, Frick KM. Long-term continuous, but not daily, environmental enrichment reduces spatial memory decline in aged male mice. Neurobiol Learn Mem United States. 2006;85:139–52.

    Article  Google Scholar 

  27. Benaroya-Milshtein N, Hollander N, Apter A, Kukulansky T, Raz N, Wilf A, et al. Environmental enrichment in mice decreases anxiety, attenuates stress responses and enhances natural killer cell activity. Eur J Neurosci France. 2004;20:1341–7.

    Article  CAS  Google Scholar 

  28. Tanaś Ł, Ostaszewski P, Iwan A. Effects of post-weaning social isolation and environment al enrichment on exploratory behavior and ankiety in Wistar rats. Acta Neurobiol Exp (Wars). 2015;75:72–9.

    Article  PubMed  Google Scholar 

  29. GBD 2016 Stroke Collaborators. Global, regional, and national burden of stroke, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. England; 2019;18:439–58

  30. Aparicio HJ, Benjamin EJ, Callaway CW, Carson AP, Cheng S, Elkind MS V, et al. Heart disease and stroke statistics-2021 update a report from the American Heart Association. Circulation. 2021;143(8):e254-e743. https://doi.org/10.1161/CIR.0000000000000950

  31. Feigin VL, Lawes CMM, Bennett DA, Barker-Collo SL, Parag V. Worldwide stroke incidence and early case fatality reported in 56 population-based studies: a systematic review. Lancet Neurol England. 2009;8:355–69.

    Article  Google Scholar 

  32. Grysiewicz RA, Thomas K, Pandey DK. 2008 Epidemiology of ischemic and hemorrhagic stroke: incidence, prevalence, mortality, and risk factors. Neurol Clin [Internet]. 2008;26:871–95. https://doi.org/10.1016/j.ncl.2008.07.003. (Elsevier Inc. Available from).

    Article  PubMed  Google Scholar 

  33. Ohlsson AL, Johansson BB. Environment influences functional outcome of cerebral infarction in rats. Stroke U S. 1995;26:644–9.

    Article  CAS  Google Scholar 

  34. Johansson BB, Belichenko PV. Neuronal plasticity and dendritic spines: effect of environmental enrichment on intact and postischemic rat brain. J Cereb Blood Flow Metab. 2002;22:89–96.

    Article  PubMed  Google Scholar 

  35. Auriat AM, Wowk S, Colbourne F. Rehabilitation after intracerebral hemorrhage in rats improves recovery with enhanced dendritic cosmplexity but no effect on cell proliferation. Behav Brain Res [Internet]. Elsevier B.V.; 2010;214:42–7. Available from: https://doi.org/10.1016/j.bbr.2010.04.025

  36. Biernaskie J, Corbett D. Enriched rehabilitative training promotes improved forelimb motor function and enhanced dendritic growth after focal ischemic injury. J Neurosci. 2001;21:5272–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Zhu Y-T, Zhang Q, Xie H-Y, Yu K-W, Xu G-J, Li S-Y, et al. Environmental enrichment combined with fasudil promotes motor function recovery and axonal regeneration after stroke. Neural Regen Res. 2021;16:2512–20.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Li MZ, Zhan Y, Yang L, Feng XF, Zou HY, Lei JF, et al. MRI evaluation of axonal remodeling after combination treatment with xiaoshuan enteric-coated capsule and enriched environment in rats after ischemic stroke. Front Physiol. 2019;10:1–18.

    Article  ADS  Google Scholar 

  39. Zhan Y, Li MZ, Yang L, Feng XF, Lei JF, Zhang N, et al. The three-phase enriched environment paradigm promotes neurovascular restorative and prevents learning impairment after ischemic stroke in rats. Neurobiol Dis [Internet]. Elsevier; 2020;146:105091. Available from: https://doi.org/10.1016/j.nbd.2020.105091

  40. Guo YS, Yuan M, Han Y, Shen XY, Gao ZK, Bi X. Effects of enriched environment on microglia and functional white matter recovery in rats with post stroke cognitive impairment. Neurochem Int. 2022;154:1–21.

    Article  Google Scholar 

  41. Yuan M, Zhang XX, Fu XC, Bi X. Enriched environment alleviates post-stroke cognitive impairment through enhancing α7-nAChR expression in rats. Arq Neuropsiquiatr. 2020;78:603–10.

    Article  PubMed  Google Scholar 

  42. Li M, Zhao Y, Zhan Y, Yang L, Feng X, Lu Y, et al. Enhanced white matter reorganization and activated brain glucose metabolism by enriched environment following ischemic stroke: micro PET/CT and MRI study. Neuropharmacology [Internet]. 2020;176:108202. https://doi.org/10.1016/j.neuropharm.2020.108202. (Elsevier Available from).

    Article  CAS  PubMed  Google Scholar 

  43. Quattromani MJ, Pruvost M, Guerreiro C, Backlund F, Englund E, Aspberg A, et al. Extracellular matrix modulation is driven by experience-dependent plasticity during stroke recovery. Mol Neurobiol Molecular Neurobiology. 2018;55:2196–213.

    Article  CAS  PubMed  Google Scholar 

  44. Nygren J, Wieloch T. Enriched environment enhances recovery of motor function after focal ischemia in mice, and downregulates the transcription factor NGFI-A. J Cereb Blood Flow Metab. 2005;25:1625–33.

    Article  CAS  PubMed  Google Scholar 

  45. Clarke J, Langdon KD, Corbett D. Early poststroke experience differentially alters periinfarct layer II and III cortex. J Cereb Blood Flow Metab. 2014;34:630–7.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Hirata K, Kuge Y, Yokota C, Harada A, Kokame K, Inoue H, et al. Gene and protein analysis of brain derived neurotrophic factor expression in relation to neurological recovery induced by an enriched environment in a rat stroke model. Neurosci Lett Ireland. 2011;495:210–5.

    Article  CAS  Google Scholar 

  47. Risedal A, Mattsson B, Dahlqvist P, Nordborg C, Olsson T, Johansson BB. Environmental influences on functional outcome after a cortical infarct in the rat. Brain Res Bull. 2002;58:315–21.

    Article  PubMed  Google Scholar 

  48. Deng YH, Dong LL, Zhang YJ, Zhao XM, He HY. Enriched environment boosts the post-stroke recovery of neurological function by promoting autophagy. Neural Regen Res. 2021;16:813–9.

    Article  CAS  PubMed  Google Scholar 

  49. Buchhold B, Mogoanta L, Suofu Y, Hamm A, Walker L, Kessler C, et al. Environmental enrichment improves functional and neuropathological indices following stroke in young and aged rats. Restor Neurol Neurosci Netherlands. 2007;25:467–84.

    CAS  Google Scholar 

  50. Zhang X, Liu JY, Liao WJ, Chen XP. Differential effects of physical and social enriched environment on angiogenesis in male rats after cerebral ischemia/reperfusion injury. Front Hum Neurosci. 2021;15:1–12.

    Article  Google Scholar 

  51. Liu J, Zheng J, Xu Y, Cao W, Wang J, Wang B, et al. Enriched environment attenuates pyroptosis to improve functional recovery after cerebral ischemia/reperfusion injury. Front Aging Neurosci. 2021;13:717644. https://doi.org/10.3389/fnagi.2021.717644

  52. Chen X, Zhang X, Xue L, Hao C, Liao W, Wan Q. Treatment with enriched environment reduces neuronal apoptosis in the periinfarct cortex after cerebral ischemia/reperfusion injury. Cell Physiol Biochem. 2017;41:1445–56.

    Article  CAS  PubMed  Google Scholar 

  53. Zhang X, Chen X-P, Lin J-B, Xiong Y, Liao W-J, Wan Q. Effect of enriched environment on angiogenesis and neurological functions in rats with focal cerebral ischemia. Brain Res Netherlands. 2017;1655:176–85.

    Article  CAS  Google Scholar 

  54. Gonçalves LV, Herlinger AL, Ferreira TAA, Coitinho JB, Pires RGW, Martins-Silva C. Environmental enrichment cognitive neuroprotection in an experimental model of cerebral ischemia: biochemical and molecular aspects. Behav Brain Res [Internet]. 2018;348:171–83. https://doi.org/10.1016/j.bbr.2018.04.023. (Elsevier Available from).

    Article  CAS  PubMed  Google Scholar 

  55. Hase Y, Craggs L, Hase M, Stevenson W, Slade J, Lopez D, et al. Effects of environmental enrichment on white matter glial responses in a mouse model of chronic cerebral hypoperfusion. J Neuroinflammation J Neuroinflammation. 2017;14:1–14.

    Google Scholar 

  56. Hase Y, Craggs L, Hase M, Stevenson W, Slade J, Chen A, et al. The effects of environmental enrichment on white matter pathology in a mouse model of chronic cerebral hypoperfusion. J Cereb Blood Flow Metab. 2018;38:151–65.

    Article  PubMed  Google Scholar 

  57. Zhou X, Chen H, Wang L, Lenahan C, Lian L, Ou Y, et al. Mitochondrial dynamics: a potential therapeutic target for ischemic stroke. Front Aging Neurosci. 2021;13:721428. https://doi.org/10.3389/fnagi.2021.721428

  58. Yu K, Kuang S, Wang C, Wang Y, Liu G, Xie H, et al. Changes in Mitochondria-Associated Protein Expression and Mitochondrial Function in Response to 2 Weeks of Enriched Environment Training After Cerebral Ischaemia-Reperfusion Injury. J Mol Neurosci. 2020;70:413–21.

    Article  CAS  PubMed  Google Scholar 

  59. Ruan L, Wang B, Zhuge Q, Jin K. Coupling of neurogenesis and angiogenesis after ischemic stroke. Brain Res [Internet] Elsevier. 2015;1623:166–73. https://doi.org/10.1016/j.brainres.2015.02.042. (Available from).

    Article  CAS  Google Scholar 

  60. Shen X, Luo L, Wang F, Yu K, Xie H, Tian S, et al. An enriched environment enhances angiogenesis surrounding the cingulum in ischaemic stroke rats. Neural Plast. 2020:8840319. https://doi.org/10.1155/2020/8840319

  61. Chen J-Y, Yu Y, Yuan Y, Zhang Y-J, Fan X-P, Yuan S-Y, et al. Enriched housing promotes post-stroke functional recovery through astrocytic HMGB1-IL-6-mediated angiogenesis. Cell Death Discov [Internet]. Nature Publishing Group; 2017;3:1–10. Available from: https://doi.org/10.1038/cddiscovery.2017.54

  62. Xie H, Yu K, Zhou N, Shen X, Tian S, Zhang B, et al. Enriched environment elicits proangiogenic mechanisms after focal cerebral ischemia. Transl Stroke Res. 2019;10:150–9.

    Article  CAS  PubMed  Google Scholar 

  63. Zhan Y, Li MZ, Yang L, Feng XF, Zhang QX, Zhang N, et al. An MRI study of neurovascular restorative after combination treatment with xiaoshuanenteric-coated capsule and enriched environment in rats after stroke. Front Neurosci. 2019;13:1–17.

    Article  Google Scholar 

  64. Xie H, Zhang Q, Zhou N, Li C, Yu K, Liu G, et al. Environmental enrichment enhances post-ischemic cerebral blood flow and functional hyperemia in the ipsilesional somatosensory cortex. Brain Res Bull. 2020;160:91–7.

    Article  CAS  PubMed  Google Scholar 

  65. Krupinski J, Kaluza J, Kumar P, Kumar S, Wang JM. Role of angiogenesis in patients with cerebral ischemic stroke. Stroke. 1994;25:1794–8.

    Article  CAS  PubMed  Google Scholar 

  66. García-Pupo L, Van San E, Delgado-Hernández R, Vanden Berghe T, Vanden BW. Emerging immune and cell death mechanisms in stroke: saponins as therapeutic candidates. Brain, Behav Immun - Heal. 2020;9:100152.

    Article  Google Scholar 

  67. Qian HZ, Zhang H, Yin LL, Zhang JJ. Postischemic housing environment on cerebral metabolism and neuron apoptosis after focal cerebral ischemia in rats. Curr Med Sci. 2018;38:656–65.

    Article  PubMed  Google Scholar 

  68. Xu GJ, Zhang Q, Li SY, Zhu YT, Yu KW, Wang CJ, et al. Environmental enrichment combined with fasudil treatment inhibits neuronal death in the hippocampal CA1 region and ameliorates memory deficits. Neural Regen Res. 2021;16:1460–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Rahman AA, Amruta N, Pinteaux E, Bix GJ. Neurogenesis after stroke: a therapeutic perspective. Transl Stroke Res Translational Stroke Res. 2021;12:1–14.

    Article  CAS  Google Scholar 

  70. Komitova M, Mattsson B, Johansson BB, Eriksson PS. Enriched environment increases neural stem/progenitor cell proliferation and neurogenesis in the subventricular zone of stroke-lesioned adult rats. Stroke. 2005;36:1278–82.

    Article  PubMed  Google Scholar 

  71. Tan XD, Liu B, Jiang Y, Yu HJ, Li CQ. Gadd45b mediates environmental enrichment-induced neurogenesis in the SVZ of rats following ischemia stroke via BDNF. Neurosci Lett [Internet]. Elsevier B.V.; 2021;745:135616. Available from: https://doi.org/10.1016/j.neulet.2020.135616

  72. Gresita A, Mihai R, Hermann DM, Amandei FS, Capitanescu B, Popa-Wagner A. Effect of environmental enrichment and isolation on behavioral and histological indices following focal ischemia in old rats. GeroScience [Internet]. Springer International Publishing; 2021; Available from: https://doi.org/10.1007/s11357-021-00432-z

  73. Tang Y, Li MY, Zhang X, Jin X, Liu J, Wei PH. Delayed exposure to environmental enrichment improves functional outcome after stroke. J Pharmacol Sci [Internet]. 2019;140:137–43. https://doi.org/10.1016/j.jphs.2019.05.002. (Elsevier Ltd Available from).

    Article  CAS  PubMed  Google Scholar 

  74. Wu X, Liu S, Hu Z, Zhu G, Zheng G, Wang G. Enriched housing promotes post-stroke neurogenesis through calpain 1-STAT3/HIF-1α/VEGF signaling. Brain Res Bull [Internet]. 2018;139:133–43. https://doi.org/10.1016/j.brainresbull.2018.02.018. (Elsevier Available from).

    Article  CAS  PubMed  Google Scholar 

  75. Zhang Y, Xu D, Qi H, Yuan Y, Liu H, Yao S, et al. Enriched environment promotes post-stroke neurogenesis through NF-κB-mediated secretion of IL-17A from astrocytes. Brain Res [Internet]. 2018;1687:20–31. https://doi.org/10.1016/j.brainres.2018.02.030. (Elsevier B.V. Available from).

    Article  CAS  PubMed  Google Scholar 

  76. Wang CJ, Wu Y, Zhang Q, Yu KW, Wang YY. An enriched environment promotes synaptic plasticity and cognitive recovery after permanent middle cerebral artery occlusion in mice. Neural Regen Res. 2019;14:462–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Wang C, Zhang Q, Yu K, Shen X, Wu Y, Wu J. Enriched environment promoted cognitive function via bilateral synaptic remodeling after cerebral ischemia. Front Neurol. 2019;10:1–11.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Singhal G, Jaehne EJ, Corrigan F, Baune BT. Cellular and molecular mechanisms of immunomodulation in the brain through environmental enrichment. Front Cell Neurosci. 2014;8:1–29.

    Article  Google Scholar 

  79. Singhal G, Morgan J, Corrigan F, Toben C, Jawahar MC, Jaehne EJ, et al. Short-term environmental enrichment is a stronger modulator of brain glial cells and cervical lymph node T cell subtypes than exercise or combined exercise and enrichment. Cell Mol Neurobiol [Internet]. 2021;41:469–86. https://doi.org/10.1007/s10571-020-00862-x. (Springer US Available from).

    Article  CAS  PubMed  Google Scholar 

  80. Singhal G, Morgan J, Jawahar MC, Corrigan F, Jaehne EJ, Toben C, et al. Duration of environmental enrichment determines astrocyte number and cervical lymph node T lymphocyte proportions but not the microglial number in middle-aged C57BL/6 mice. Front Cell Neurosci. 2020;14:1–12.

    Article  Google Scholar 

  81. Ruscher K, Johannesson E, Brugiere E, Erickson A, Rickhag M, Wieloch T. Enriched environment reduces apolipoprotein E (ApoE) in reactive astrocytes and attenuates inflammation of the peri-infarct tissue after experimental stroke. J Cereb Blood Flow Metab [Internet]. 2009;29:1796–805. https://doi.org/10.1038/jcbfm.2009.96. (Nature Publishing Group Available from).

    Article  CAS  PubMed  Google Scholar 

  82. Ruscher K, Kuric E, Liu Y, Walter HL, Issazadeh-Navikas S, Englund E, et al. Inhibition of CXCL12 signaling attenuates the postischemic immune response and improves functional recovery after stroke. J Cereb Blood Flow Metab. 2013;33:1225–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Zhong Z, Xu P, Wen J, Li X, Zhang X. Enriched environment regulates dendritic cells to alleviate inflammation in cerebral infarction lesions. Comput Math Methods Med. 2021;2021:8–14.

    Article  Google Scholar 

  84. Quattromani MJ, Cordeau P, Ruscher K, Kriz J, Wieloch T. Enriched housing down-regulates the Toll-like receptor 2 response in the mouse brain after experimental stroke. Neurobiol Dis [Internet]. 2014;66:66–73. https://doi.org/10.1016/j.nbd.2014.02.010. (Elsevier Inc. Available from:).

    Article  CAS  PubMed  Google Scholar 

  85. Zhang X, Yuan M, Yang S, Chen X, Wu J, Wen M, et al. Enriched environment improves post-stroke cognitive impairment and inhibits neuroinflammation and oxidative stress by activating Nrf2-ARE pathway. Int J Neurosci [Internet]. 2021;131:641–9. https://doi.org/10.1080/00207454.2020.1797722. (Taylor & Francis Available from).

    Article  CAS  PubMed  Google Scholar 

  86. Duris K, Lipkova J, Jurajda M. Cholinergic anti-inflammatory pathway and stroke [Internet]. Curr. Drug Deliv. 2017. p. 449–57. Available from: http://www.eurekaselect.com/node/149676/article

  87. Neumann S, Shields NJ, Balle T, Chebib M, Clarkson AN. Innate immunity and inflammation post-stroke: An α7-nicotinic agonist perspective. Int J Mol Sci. 2015;16:29029–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Xu P, Zhang X, Liu Q, Xie Y, Shi X, Chen J, et al. Microglial TREM-1 receptor mediates neuroinflammatory injury via interaction with SYK in experimental ischemic stroke. Cell Death Dis [Internet]. 2019;10:555. https://doi.org/10.1038/s41419-019-1777-9. (Available from).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Lu L-Q, Tian J, Luo X-J, Peng J. Targeting the pathways of regulated necrosis: a potential strategy for alleviation of cardio-cerebrovascular injury. Cell Mol Life Sci Switzerland. 2021;78:63–78.

    Article  CAS  Google Scholar 

  90. Kempermann G. Environmental enrichment, new neurons and the neurobiology of individuality. Nat Rev Neurosci [Internet]. 2019;20:235–45. https://doi.org/10.1038/s41583-019-0120-x. (Springer US Available from).

    Article  CAS  PubMed  Google Scholar 

  91. Guan JS, Haggarty SJ, Giacometti E, Dannenberg JH, Joseph N, Gao J, et al. HDAC2 negatively regulates memory formation and synaptic plasticity. Nature Nature Publishing Group. 2009;459:55–60.

    CAS  ADS  Google Scholar 

  92. Lin YH, Yao MC, Wu HY, Dong J, Ni HY, Kou XL, et al. HDAC2 (Histone deacetylase 2): a critical factor in environmental enrichment-mediated stroke recovery. J Neurochem. 2020;155:679–96.

    Article  CAS  PubMed  Google Scholar 

  93. Yang X, Wu Q, Zhang L, Feng L. Inhibition of histone deacetylase 3 (Hdac3) mediates ischemic preconditioning and protects cortical neurons against ischemia in rats. Front Mol Neurosci. 2016;9:1–14.

    Article  Google Scholar 

  94. Wang X, Chen A, Wu H, Ye M, Cheng H, Jiang X, et al. Enriched environment improves post-stroke cognitive impairment in mice by potential regulation of acetylation homeostasis in cholinergic circuits. Brain Res. 2016;1650:232–42.

    Article  CAS  PubMed  Google Scholar 

  95. Guo JU, Kitabatake Y, Chang M, Pow-anpongkul N, Flavell RA, Lu B, et al. Neuronal activity–induced Gadd45b promotes epigenetic DNA demethylation and adult neurogenesis. Science (80- ). 2009;178:2007–10.

  96. Liu B, Zhang YH, Jiang Y, Li LL, Chen Q, He GQ, et al. Gadd45b is a novel mediator of neuronal apoptosis in ischemic stroke. Int J Biol Sci. 2015;11:353–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Janssen H, Bernhardt J, Collier JM, Sena ES, McElduff P, Attia J, et al. An enriched environment improves sensorimotor function post-ischemic stroke. Neurorehabil Neural Repair United States. 2010;24:802–13.

    Article  Google Scholar 

  98. De Boer A, Storm A, Gomez-Soler M, Smolders S, Rué L, Poppe L, et al. Environmental enrichment during the chronic phase after experimental stroke promotes functional recovery without synergistic effects of EphA4 targeted therapy. Hum Mol Genet. 2020;29:605–17.

    Article  PubMed  Google Scholar 

  99. Yu KW, Wang CJ, Wu Y, Wang YY, Wang NH, Kuang SY, et al. An enriched environment increases the expression of fibronectin type III domain-containing protein 5 and brain-derived neurotrophic factor in the cerebral cortex of the ischemic mouse brain. Neural Regen Res. 2020;15:1671–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Jeffers MS, Corbett D. Synergistic effects of enriched environment and task-specific reach training on poststroke recovery of motor function. Stroke. 2018;49:1496–503.

    Article  PubMed  Google Scholar 

  101. Caliaperumal J, Colbourne F. Rehabilitation improves behavioral recovery and lessens cell death without affecting iron, ferritin, transferrin, or inflammation after intracerebral hemorrhage in rats. Neurorehabil Neural Repair. 2014;28:395–404.

    Article  PubMed  Google Scholar 

  102. MacLellan CL, Plummer N, Silasi G, Auriat AM, Colbourne F. Rehabilitation promotes recovery after whole blood-induced intracerebral hemorrhage in rats. Neurorehabil Neural Repair. 2011;25:477–83.

    Article  PubMed  Google Scholar 

  103. Auriat AM, Colbourne F. Delayed rehabilitation lessens brain injury and improves recovery after intracerebral hemorrhage in rats. Brain Res [Internet]. 2009;1251:262–8. https://doi.org/10.1016/j.brainres.2008.11.038. (Elsevier B.V. Available from).

    Article  CAS  PubMed  Google Scholar 

  104. Yuan M, Guo Y, Han Y, Gao Z, Shen X, Bi X. Effectiveness and mechanisms of enriched environment in post-stroke cognitive impairment. Behav Brain Res [Internet]. 2021;410:113357. https://doi.org/10.1016/j.bbr.2021.113357. (Elsevier B.V. Available from).

    Article  PubMed  Google Scholar 

  105. Coleman ER, Moudgal R, Lang K, Hyacinth HI, Awosika OO, Kissela BM, et al. Early rehabilitation after stroke: a narrative review. Curr Atheroscler Rep. Current Atherosclerosis Reports; 2017;19(12):59. https://doi.org/10.1007/s11883-017-0686-6

  106. Murphy TH, Corbett D. Plasticity during stroke recovery: from synapse to behaviour. Nat Rev Neurosci England. 2009;10:861–72.

    Article  CAS  Google Scholar 

  107. Cramer SC. Repairing the human brain after stroke: I Mechanisms of spontaneous recovery. Ann Neurol. 2008;63:272–87.

    Article  PubMed  Google Scholar 

  108. Risedal A, Zeng J, Johansson BB. Early training may exacerbate brain damage after focal brain ischemia in the rat. J Cereb Blood Flow Metab. 1999;19:997–1003.

    Article  CAS  PubMed  Google Scholar 

  109. Johansson BB, Ohlsson AL. Environment, social interaction, and physical activity as determinants of functional outcome after cerebral infarction in the rat. Exp Neurol. 1996;139:322–7.

    Article  CAS  PubMed  Google Scholar 

  110. Komitova M, Zhao LR, Gidö G, Johansson BB, Eriksson P. Postischemic exercise attenuates whereas enriched environment has certain enhancing effects on lesion-induced subventricular zone activation in the adult rat. Eur J Neurosci. 2005;21:2397–405.

    Article  PubMed  Google Scholar 

  111. Wahl AS, Erlebach E, Brattoli B, Büchler U, Kaiser J, Ineichen BV, et al. Early reduced behavioral activity induced by large strokes affects the efficiency of enriched environment in rats. J Cereb Blood Flow Metab. 2019;39:2022–34.

    Article  PubMed  Google Scholar 

  112. Biernaskie J, Chernenko G, Corbett D. Efficacy of rehabilitative experience declines with time after focal ischemic brain injury. J Neurosci. 2004;24:1245–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Xie H, Wu Y, Jia J, Liu G, Zhang F, Zhang Q, et al. Enriched environment preconditioning induced brain ischemic tolerance without reducing infarct volume and edema: the possible role of enrichment-related physical activity increase. Brain Res. 2013;1508:63–72.

    Article  CAS  PubMed  Google Scholar 

  114. Yu K, Wu Y, Hu Y, Zhang Q, Xie H, Liu G, et al. Prior exposure to enriched environment reduces nitric oxide synthase after transient MCAO in rats. Neurotoxicology. 2013;39:146–52.

    Article  CAS  PubMed  Google Scholar 

  115. Keiner S, Wurm F, Kunze A, Witte OW, Redecker C. Rehabilitative therapies differentially alter proliferation and survival of glial cell populations in the perilesional zone of cortical infarcts. Glia. 2008;56:516–27.

    Article  PubMed  Google Scholar 

  116. Clarke J, Mala H, Windle V, Chernenko G, Corbett D. The effects of repeated rehabilitation tune-ups on functional recovery after focal ischemia in rats. Neurorehabil Neural Repair. 2009;23:886–94.

    Article  PubMed  Google Scholar 

  117. Leger M, Paizanis E, Dzahini K, Quiedeville A, Bouet V, Cassel JC, et al. Environmental enrichment duration differentially affects behavior and neuroplasticity in adult mice. Cereb Cortex. 2015;25:4048–61.

    Article  PubMed  Google Scholar 

  118. Lee H, Yun H, Ding Y. Timing is everything: exercise therapy and remote ischemic conditioning for acute ischemic stroke patients. Brain Circ. 2021;7:178.

    Article  PubMed  PubMed Central  Google Scholar 

  119. Shen J, Huber M, Zhao EY, Peng C, Li F, Li X, et al. Early rehabilitation aggravates brain damage after stroke via enhanced activation of nicotinamide adenine dinucleotide phosphate oxidase. Brain Res [Internet]. 2016;1648:266–76. https://doi.org/10.1016/j.brainres.2016.08.001. (Elsevier Available from).

    Article  CAS  PubMed  Google Scholar 

  120. Takeuchi N, Izumi SI. Maladaptive plasticity for motor recovery after stroke: Mechanisms and approaches. Neural Plast. 2012;2012:359728. https://doi.org/10.1155/2012/359728

  121. Jeffers MS, Corbett D. Synergistic effects of enriched environment and task-specific reach training on poststroke recovery of motor function. Stroke United States. 2018;49:1496–503.

    Article  Google Scholar 

  122. Rosbergen ICM, Tonello I, Clark RA, Grimley RS. Does hospital design impact on patient activity levels and time spent alone? Disabil Rehabil [Internet]. Taylor & Francis; 2020;0:1–8. Available from: https://doi.org/10.1080/09638288.2020.1861117

  123. Lipson-Smith R, Churilov L, Newton C, Zeeman H, Bernhardt J. A Framework for designing inpatient stroke rehabilitation facilities: a new approach using interdisciplinary value-focused thinking. Heal Environ Res Des J. 2019;12:142–58.

    Google Scholar 

  124. Lipson-Smith R, Pflaumer L, Elf M, Blaschke SM, Davis A, White M, et al. Built environments for inpatient stroke rehabilitation services and care: a systematic literature review. BMJ Open. 2021;11:1–11.

    Article  Google Scholar 

  125. Jones F, Gombert K, Honey S, Cloud G, Harris R, Macdonald A, et al. Addressing inactivity after stroke: the collaborative rehabilitation in acute stroke (CREATE) study. Int J Stroke. 2020;0:1–14.

    Google Scholar 

  126. Clarke D, Gombert-Waldron K, Honey S, Cloud G, Harris R, MacDonald A, et al. Co-designing organisational improvements and interventions to increase inpatient activity in four stroke units in England: a mixed-methods process evaluation using normalisation process theory. BMJ Open. 2021;11:1–16.

    Article  Google Scholar 

  127. Janssen H, Ada L, Middleton S, Pollack M, Nilsson M, Churilov L, et al. Altering the rehabilitation environment to improve stroke survivor activity: a phase II trial. Int J Stroke. 2021;0:1–9.

    Google Scholar 

  128. Rosbergen ICM, Grimley RS, Hayward KS, Walker KC, Rowley D, Campbell AM, et al. Embedding an enriched environment in an acute stroke unit increases activity in people with stroke: a controlled before-after pilot study. Clin Rehabil. 2017;31:1516–28.

    Article  PubMed  Google Scholar 

  129. Janssen H, Ada L, Bernhardt J, McElduff P, Pollack M, Nilsson M, et al. An enriched environment increases activity in stroke patients undergoing rehabilitation in a mixed rehabilitation unit: a pilot non-randomized controlled trial. Disabil Rehabil. 2014;36:255–62.

    Article  PubMed  Google Scholar 

  130. Khan F, Amatya B, Elmalik A, Lowe M, Ng L, Reid I, et al. An enriched environmental programme during inpatient neuro-rehabilitation: a randomized controlled trial. J Rehabil Med. 2016;48:417–25.

    Article  PubMed  Google Scholar 

  131. Bernhardt J, Dewey H, Thrift A, Donnan G. Inactive and alone: physical activity within the first 14 days of acute stroke unit care. Stroke. 2004;35:1005–9.

    Article  PubMed  Google Scholar 

  132. Chen E, Viktorisson A, Danielsson A, Palstam A, Sunnerhagen KS. Levels of physical activity in acute stroke patients treated at a stroke unit: a prospective, observational study. J Rehabil Med. 2020;52(4):jrm00041. https://doi.org/10.2340/16501977-2671

  133. Rosbergen ICM, Grimley RS, Hayward KS, Walker KC, Rowley D, Campbell AM, et al. The effect of an enriched environment on activity levels in people with stroke in an acute stroke unit: Protocol for a before-after pilot study. Pilot Feasibility Stud [Internet]. 2016;2:1–6. https://doi.org/10.1186/s40814-016-0081-z. (Available from:).

    Article  Google Scholar 

  134. Fitzsimons CF, Nicholson SL, Morris J, Mead GE, Chastin S, Niven A. Stroke survivors’ perceptions of their sedentary behaviours three months after stroke. Disabil Rehabil [Internet]. 2020;1:1–13. https://doi.org/10.1080/09638288.2020.1768304. (Taylor & Francis Available from).

    Article  Google Scholar 

  135. Simpson DB, Breslin M, Cumming T, de Zoete SA, Gall SL, Schmidt M, et al. Sedentary time and activity behaviors after stroke rehabilitation: changes in the first 3 months home. Top Stroke Rehabil [Internet]. 2021;28:42–51. https://doi.org/10.1080/10749357.2020.1783917. (Taylor & Francis Available from).

    Article  PubMed  Google Scholar 

  136. Luker J, Lynch E, Bernhardsson S, Bennett L, Bernhardt J. Stroke survivors’ experiences of physical rehabilitation: a systematic review of qualitative studies. Arch Phys Med Rehabil [Internet]. 2015;96:1698-1708.e10. https://doi.org/10.1016/j.apmr.2015.03.017. (Elsevier Ltd Available from).

    Article  PubMed  Google Scholar 

  137. Janssen H, Ada L, Karayanidis F, Drysdale K, Mcelduff P, Pollack M, et al. Translating the use of an enriched environment poststroke from bench to bedside: Study design and protocol used to test the feasibility of environmental enrichment on stroke patients in rehabilitation. Int J Stroke. 2012;7:521–6.

    Article  CAS  PubMed  Google Scholar 

  138. Manimmanakorn N, Arrayawichanon P, Wattanapun P, Nuntharuksa C, Kuptniratsaikul V. Age-related rehabilitation outcome in stroke patients. J Med Assoc Thail. 2008;91:388–93.

    Google Scholar 

  139. Jarvis HL, Brown SJ, Price M, Butterworth C, Groenevelt R, Jackson K, et al. Return to employment after stroke in young adults. Stroke [Internet]. 2019;50:3198–204. https://doi.org/10.1161/STROKEAHA.119.025614. (American Heart Association Available from:).

    Article  PubMed  PubMed Central  Google Scholar 

  140. Okazaki T, Ebihara S, Mori T, Izumi S, Ebihara T. Association between sarcopenia and pneumonia in older people. Geriatr Gerontol Int [Internet]. 2020;20:7–13. https://doi.org/10.1111/ggi.13839. (John Wiley & Sons, Ltd; Available from).

    Article  PubMed  Google Scholar 

  141. American Psychological Association WG on the OA. What practitioners should know about working with older adults.Prof Psychol Res Pract. US: American Psychological Association; 1998;29:413–27

  142. Hess TM. Selective engagement of cognitive resources: motivational influences on older adults’ cognitive functioning. Perspect Psychol Sci [Internet]. 2014;9:388–407. https://doi.org/10.1177/1745691614527465. (SAGE Publications Inc; Available from).

    Article  PubMed  PubMed Central  Google Scholar 

  143. Shen F, Jiang L, Han F, Degos V, Chen S, Su H. Increased inflammatory response in old mice is associated with more severe neuronal injury at the acute stage of ischemic stroke. Aging Dis. 2018;10:12–22.

    Google Scholar 

  144. Kolb B, Gibb R. Environmental enrichment and cortical injury: behavioral and anatomical consequences of frontal cortex lesions. Cereb Cortex [Internet]. 1991;1:189–98. https://doi.org/10.1093/cercor/1.2.189. (Available from).

    Article  CAS  PubMed  Google Scholar 

  145. Rojas JJ, Deniz BF, Miguel PM, Diaz R, Hermel É do ES, Achaval M, et al. Effects of daily environmental enrichment on behavior and dendritic spine density in hippocampus following neonatal hypoxia-ischemia in the rat. ExpNeurol [Internet]. Elsevier Inc.; 2013;241:25–33. Available from: https://doi.org/10.1016/j.expneurol.2012.11.026

  146. Frick KM, Stearns NA, Pan J-Y, Berger-Sweeney J. Effects of environmental enrichment on spatial memory and neurochemistry in middle-aged mice. Learn Mem United States. 2003;10:187–98.

    Article  Google Scholar 

  147. Buga AM, Bălşeanu A, Popa-Wagner A, Mogoantă L. Strategies to improve post-stroke behavioral recovery in aged subjects. Rom J Morphol Embryol [Internet]. Department of Neurology, University of Greifswald, Germany.; 2009;50:559–82. Available from: http://europepmc.org/abstract/MED/19942950

  148. Li F, Geng X, Huber C, Stone C, Ding Y. In search of a dose: the functional and molecular effects of exercise on post-stroke rehabilitation in rats. Front Cell Neurosci. 2020;14:1–12.

    Article  CAS  Google Scholar 

  149. Qin H, Reid I, Gorelik A, Ng L. Environmental enrichment for stroke and other non-progressive brain injury. Cochrane Database Syst Rev. 2021;2021.

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Acknowledgements

We would like to thank CAPES, CNPq, and FAPERGS for their financial support.

Funding

This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001; Conselho Nacional de Pesquisa e Desenvolvimento (CNPq)—Grant Numbers 306644/ 2016–9 and 423884/2018–2; Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS).

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  1. Programa de Pós-Graduação Em Biologia Celular E Molecular, Laboratório deBiologiaCelular ETecidual, Pontifical Catholic University of Rio Grande Do Sul, PUCRS. Escola de Ciências da Saúde E da Vida, Av. Ipiranga 6681, Prédio 12C, Sala 104, Porto Alegre, Rio Grande Do Sul, CEP, 90619-900, Brazil

    Laura Tartari Neves, Lisiê Valéria Paz, Andréa Wieck, Régis Gemerasca Mestriner, Valentina Aguiar Cardozo de Miranda Monteiro & Léder Leal Xavier

  2. Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Av. Ipiranga, 6690 - Jardim Botânico, Porto Alegre, RS, 90610-000, Brazil

    Andréa Wieck

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L.L.X and R.G.M. - suggested the topic to be approached and how the manuscript should be developed. Also performed the final reviews and orientation. L.T.N. and L.V.P. - developed the figures in Canva and PowerPoint, based on the text and suggestions of A.W. L.T.N., L.V.P. and V.A.C.M.M - performed the literature review. Discussed the topic and wrote the manuscript. A.W. - discussed the topics, corrected the ,manuscript, and wrote.

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Neves, L.T., Paz, L.V., Wieck, A. et al. Environmental Enrichment in Stroke Research: an Update. Transl. Stroke Res. 15, 339–351 (2024). https://doi.org/10.1007/s12975-023-01132-w

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