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Effect of environmental enrichment on behavioral and morphological outcomes following neonatal hypoxia-ischemia in rodent models: A systematic review and meta-analysis

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Abstract

Neonatal hypoxia-ischemia (HI) is a major cause of mortality and morbidity in newborns and, despite recent advances in neonatal intensive care, there is no definitive treatment for this pathology. Once preclinical studies have shown that environmental enrichment (EE) seems to be a promising therapy for children with HI, the present study conducts a systematic review and meta-analysis of articles with EE in HI rodent models focusing on neurodevelopmental reflexes, motor and cognitive function as well as brain damage. The protocol was registered a priori at PROSPERO. The search was conducted in PubMed, Embase and PsycINFO databases, resulting in the inclusion of 22 articles. Interestingly, EE showed a beneficial impact on neurodevelopmental reflexes (SMD= -0.73, CI= [-0.98; -0.47], p< 0.001, I2= 0.0%), motor function (SMD= -0.55, CI= [-0.81; -0.28], p< 0.001, I2= 62.6%), cognitive function (SMD= -0.93, CI= [-1.14; -0.72], p< 0.001, I2= 27.8%) and brain damage (SMD= -0.80, CI= [-1.03; -0.58], p< 0.001, I2= 10.7%). The main factors that potentiate EE positive effects were enhanced study quality, earlier age at injury as well as earlier start and longer duration of EE exposure. Overall, EE was able to counteract the behavioral and histological damage induced by the lesion, being a promising therapeutic strategy for HI.

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Availability of data and materials

The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This study was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).

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  1. Graduate Program in Biological Sciences: Physiology, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

    L. E Durán-Carabali

  2. Graduate Program in Biological Sciences: Biochemistry, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

    F. K. Odorcyk

  3. Division of Child Development and Growth, Department of Pediatrics, Gynecology and Obstetrics, School of Medicine, University of Geneva, Geneva, Switzerland

    E. F. Sanches

  4. Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2600, anexo, Porto Alegre, RS, CEP 90035-003, Brazil

    M. M de Mattos & C. A. Netto

  5. Medicine school, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil

    F. Anschau

  6. Graduation Program on Evaluation and Production of Technologies for the Brazilian National Health System, Porto Alegre, Brazil

    F. Anschau

  7. Department of Physiology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

    C. A. Netto

Authors
  1. L. E Durán-Carabali
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  2. F. K. Odorcyk
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  3. E. F. Sanches
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  4. M. M de Mattos
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  5. F. Anschau
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  6. C. A. Netto
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Contributions

Conception and design of research: D-C.LE, O.FK, literature search: D-C.LE, O.F, S.EF, studies evaluation: O.F, dM.MM, data extraction: D-C.LE, O.FK, dM.MM, analyzed data: D-C.LE, drafted manuscript: D-C.LE, O.FK, S.EF, A.F, edited and revised manuscript: D.C-LE, A.F, N.CA.

Corresponding authors

Correspondence to L. E Durán-Carabali or C. A. Netto.

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This article is a review; therefore, it does not contain any experiments with human participants or animals performed by any of the authors.

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Durán-Carabali, L.E., Odorcyk, F.K., Sanches, E.F. et al. Effect of environmental enrichment on behavioral and morphological outcomes following neonatal hypoxia-ischemia in rodent models: A systematic review and meta-analysis. Mol Neurobiol 59, 1970–1991 (2022). https://doi.org/10.1007/s12035-022-02730-9

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