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Tissue Injury and Astrocytic Reaction, But Not Cognitive Deficits, Are Dependent on Hypoxia Duration in Very Immature Rats Undergoing Neonatal Hypoxia–Ischemia

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Abstract

Preterm birth and hypoxia–ischemia (HI) are major causes of neonatal death and neurological disabilities in newborns. The widely used preclinical HI model combines carotid occlusion with hypoxia exposure; however, the relationship between different hypoxia exposure periods with brain tissue loss, astrocyte reactivity and behavioral impairments following HI is lacking. Present study evaluated HI-induced behavioral and morphological consequences in rats exposed to different periods of hypoxia at postnatal day 3. Wistar rats of both sexes were assigned into four groups: control group, HI-120 min, HI-180 min and HI-210 min. Neurodevelopmental reflexes, exploratory abilities and cognitive function were assessed. At adulthood, tissue damage and reactive astrogliosis were measured. Animals exposed to HI-180 and HI-210 min had delayed neurodevelopmental reflexes compared to control group. Histological assessment showed tissue loss that was restricted to the ipsilateral hemisphere in lower periods of hypoxia exposure (120 and 180 min) but affected both hemispheres when 210 min was used. Reactive astrogliosis was increased only after 210 min of hypoxia. Interestingly, cognitive deficits were induced regardless the duration of hypoxia and there were correlations between behavioral parameters and cortex, hippocampus and corpus callosum volumes. These results show the duration of hypoxia has a close relationship with astrocytic response and tissue damage progression. Furthermore, the long-lasting cognitive memory deficit and its association with brain structures beyond the hippocampus suggests that complex anatomical changes should be involved in functional alterations taking place as hypoxia duration is increased, even when the cognitive impairment limit is achieved.

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Acknowledgements

The authors thank the staff of Reproduction and Laboratory Animal Research Center from Biochemistry Department UFRGS.

Funding

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

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Authors and Affiliations

  1. Post-graduation Program of Physiology, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul (UFRGS), Rua Ramiro Barcelos 2600, anexo, Porto Alegre, RS, CEP 90035-003, Brazil

    L. E. Durán-Carabali, F. K. Odorcyk & C. A. Netto

  2. Post-graduation Program of Neuroscience, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil

    F. Nicola & C. A. Netto

  3. Biochemistry Department, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil

    E. F. Sanches, D. Aristimunha & C. A. Netto

  4. Neurorehabilitation and Neural Repair Research Group, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil

    R. G. Mestriner & L. Reichert

  5. Rehabilitation Sciences Graduate Program, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, Brazil

    A. S. Pagnussat

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  1. L. E. Durán-Carabali
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Durán-Carabali, L.E., Sanches, E.F., Odorcyk, F.K. et al. Tissue Injury and Astrocytic Reaction, But Not Cognitive Deficits, Are Dependent on Hypoxia Duration in Very Immature Rats Undergoing Neonatal Hypoxia–Ischemia. Neurochem Res 44, 2631–2642 (2019). https://doi.org/10.1007/s11064-019-02884-4

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