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Traumatic brain injury alters long-term hippocampal neuron morphology in juvenile, but not immature, rats

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Abstract

Purpose

Pediatric traumatic brain injury (TBI) represents a prominent yet understudied medical condition that can profoundly impact brain development. As the juvenile injured brain matures in the wake of neuropathological cascades during potentially critical periods, circuit alterations may explain neurological consequences, including cognitive deficits. We hypothesize that experimental brain injury in juvenile rats, with behavioral deficits that resolve, will lead to quantifiable structural changes in hippocampal neurons at chronic time points post-injury.

Methods

Controlled cortical impact (CCI), a model of focal TBI with contusion, was used to induce brain injury on post-natal day (PND) 17 juvenile rats. The histological consequence of TBI was quantified in regions of the hippocampus at post-injury day 28 (PID28) on sections stained using a variation of the Golgi-Cox staining method. Individual neuronal morphologies were digitized from the dentate gyrus (DG), CA3, and CA1 regions.

Results

Soma area in the ipsilateral injured DG and CA3 regions of the hippocampus increased significantly at PID28 in comparison to controls. In CA1, dendritic length and dendritic branching decreased significantly in comparison to controls and the contralateral hemisphere, without change in soma area. To extend the study, we examined neuronal morphology in rats with CCI at PND7. On PID28 after CCI on PND7 rats, CA1 neurons showed no injury-induced change in morphology, potentially indicating an age-dependent morphological response to injury.

Conclusions

Long-lasting structural alterations in hippocampal neurons of brain-injured PND17 juvenile animals, but not PND7 immature animals, suggest differential plasticity depending on age-at-injury, with potential consequences for later function.

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Acknowledgments

The authors would like to sincerely thank the contributions of Dan Santone for the preliminary studies that made this research possible. Also, Rachel K. Rowe, PhD, Jordan L. Harrison, Jenna M. Ziebell, PhD, and the rest of the Translational Neurotrauma Research Team–Phoenix, AZ, provided thoughtful feedback on early drafts of the manuscript. These experiments were carried out at the University of Pittsburgh and analyzed and prepared for publication at the University of Arizona College of Medicine–Phoenix. This work was supported by the Walter L. Copeland Fund of the Pittsburgh Foundation Funding for Cranial Research and Phoenix Children’s Hospital Mission Support Funds.

Conflict of interest

The authors would like to disclose that there exist no conflicts of interest.

Author information

Authors and Affiliations

  1. Barrow Neurological Institute, Phoenix Children’s Hospital, Ambulatory Building B, 4th Floor, 1919 East Thomas Road, Phoenix, AZ, 85016, USA

    Eric M. Casella, Theresa Currier Thomas, Jonathan Lifshitz & P. David Adelson

  2. Department of Child Health, University of Arizona College of Medicine–Phoenix, Phoenix, AZ, 85004, USA

    Eric M. Casella, Theresa Currier Thomas, Jonathan Lifshitz & P. David Adelson

  3. Phoenix VA Healthcare System, Phoenix, AZ, 85012, USA

    Theresa Currier Thomas & Jonathan Lifshitz

  4. Neuroscience Program, Arizona State University, Tempe, AZ, 85287, USA

    Jonathan Lifshitz & P. David Adelson

  5. School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ, 85287, USA

    P. David Adelson

  6. Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA, 15260, USA

    J. Patrick Card

  7. Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA, 15213, USA

    Wendy Fellows-Mayle

  8. Medical University of South Carolina, Charleston, SC, 29412, USA

    Dana L. Vanino

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  1. Eric M. Casella
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  2. Theresa Currier Thomas
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  3. Dana L. Vanino
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  4. Wendy Fellows-Mayle
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  5. Jonathan Lifshitz
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  6. J. Patrick Card
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  7. P. David Adelson
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Corresponding author

Correspondence to P. David Adelson.

Additional information

Eric Casella and Theresa Currier Thomas contributed equally to this paper

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Casella, E.M., Thomas, T.C., Vanino, D.L. et al. Traumatic brain injury alters long-term hippocampal neuron morphology in juvenile, but not immature, rats. Childs Nerv Syst 30, 1333–1342 (2014). https://doi.org/10.1007/s00381-014-2446-z

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  • DOI: https://doi.org/10.1007/s00381-014-2446-z

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