Molecular Neurobiology

, Volume 55, Issue 5, pp 3627–3641 | Cite as

Prenatal and Early Postnatal Environmental Enrichment Reduce Acute Cell Death and Prevent Neurodevelopment and Memory Impairments in Rats Submitted to Neonatal Hypoxia Ischemia

  • L. E. Durán-Carabali
  • D. M. Arcego
  • F. K. Odorcyk
  • L. Reichert
  • J. L. Cordeiro
  • E. F. Sanches
  • L. D. Freitas
  • C. Dalmaz
  • A. Pagnussat
  • C. A. Netto


Environmental enrichment (EE) is an experimental strategy to attenuate the negative effects of different neurological conditions including neonatal hypoxia ischemia encephalopathy (HIE). The aim of the present study was to investigate the influence of prenatal and early postnatal EE in animals submitted to neonatal HIE model at postnatal day (PND) 3. Wistar rats were housed in EE or standard conditions (SC) during pregnancy and lactation periods. Pups of both sexes were assigned to one of four experimental groups, considering the early environmental conditions and the injury: SC-Sham, SC-HIE, EE-sham, and EE-HIE. The offspring were euthanized at two different time points: 48 h after HIE for biochemical analyses or at PND 67 for histological analyses. Behavioral tests were performed at PND 7, 14, 21, and 60. Offspring from EE mothers had better performance in neurodevelopmental and spatial memory tests when compared to the SC groups. HIE animals showed a reduction of IGF-1 and VEGF in the parietal cortex, but no differences in BDNF and TrkB levels were found. EE-HIE animals showed reduction in cell death, lower astrocyte reactivity, and an increase in AKTp levels in the hippocampus and parietal cortex. In addition, the EE was also able to prevent the hippocampus tissue loss. Altogether, present findings point to the protective potential of the prenatal and early postnatal EE in attenuating molecular and histological damage, as well as the neurodevelopmental impairments and the cognitive deficit, caused by HIE insult at PND 3.


Prematurity Gestation Pre-weaning period Environmental stimulation Cell death Neurodevelopment Memory 



Protein kinase B


Phosphorylate protein kinase B


Blood-brain barrier


Analysis of variance


Brain-derived neurotrophic factor


Cysteinyl-aspartate proteases


Standard condition


Environmental enrichment


Elevate plus maze


Fraction of inspired oxygen


Gestational day


Glial fibrillary acid protein


Hypoxia ischemia encephalopathy


Insulin-like growth factor 1


Poly (ADP-ribose) polymerase-1


Postnatal day


Tris buffer saline


Tropomyosin receptor kinase B


Tween tris buffer saline


Vascular endothelial growth factor



This study was partly supported by financial resources from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). The authors also thank the staff of the Reproduction and Laboratory Animal Research Center from Biochemistry Department–UFRGS.

Compliance with Ethical Standards

The experimental procedures were approved by the Ethics committee of the Universidade Federal do Rio Grande do Sul (no 28641). Animal care followed the guidelines of the Brazilian Society of Science in Laboratory Animals—Law no 11.794; and the recommendation of the Council for International Organizations of Medical Sciences (CIOMS - Publication 85-23, 1985).

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12035_2017_604_MOESM1_ESM.docx (15 kb)
Supplementary Table 1 (DOCX 15 kb).


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • L. E. Durán-Carabali
    • 1
  • D. M. Arcego
    • 2
  • F. K. Odorcyk
    • 1
  • L. Reichert
    • 3
  • J. L. Cordeiro
    • 4
  • E. F. Sanches
    • 2
  • L. D. Freitas
    • 2
  • C. Dalmaz
    • 2
    • 3
  • A. Pagnussat
    • 5
  • C. A. Netto
    • 1
    • 2
    • 4
  1. 1.Post-graduation Program of Physiology, Institute of Health ScienceUniversidade Federal do Rio Grande do Sul (UFRGS)Porto AlegreBrazil
  2. 2.Department of Biochemistry, Institute of Health ScienceUniversidade Federal do Rio Grande do Sul (UFRGS)Porto AlegreBrazil
  3. 3.Neurorehabilitation and Neural Repair Research GroupPontifícia Universidade Católica do Rio Grande do Sul (PUCRS)Porto AlegreBrazil
  4. 4.Post-graduation Program of Neuroscience, Institute of Health Science|Universidade Federal do Rio Grande do Sul (UFRGS)Porto AlegreBrazil
  5. 5.Rehabilitation Sciences Graduate ProgramUniversidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA)Porto AlegreBrazil

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