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Pathological changes of the hippocampus and cognitive dysfunction following frontal lobe surgery in a rat model

  • Experimental Research - Brain Injury
  • Published:
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Abstract

Background

Postoperative cognitive dysfunction (POCD) is a known complication after intracranial surgery. Impaired hippocampal neurogenesis has been associated with cognitive dysfunction in animal models.

Methods

In order to assess hippocampal changes after brain surgery, a frontal lobe corticectomy was performed in ten adult Wistar rats (group 4). Three different control groups (n = 10 each) included no treatment (G1), general anesthesia alone (G2), and craniectomy without dural opening (G3). Twenty-four hours after surgery, half of the animals were killed, and the mRNA levels for IL-6, TNF-α, and brain-derived growth factor (BDNF) in the contralateral hippocampus were assessed by qPCR. Seven days later, the remaining animals underwent anxiety and memory testing. Afterwards, the number of immature neurons in the hippocampal cortex was measured by doublecortin (DCX) staining.

Results

Twenty-four hours after surgery, mRNA levels of IL-6 and TNF-α increased and BDNF decreased in both surgical groups G3 and G4 (p = 0.012). Cognitive tests demonstrated an increase in anxiety levels and memory impairment in surgical groups compared with non-surgical animals. These changes correlated with an inhibition of hippocampal neurogenesis evidenced by a decreased number of new neurons (mean ± SD for G1-4: 66.4 ± 24; 57.6 ± 22.2; 21.3 ± 3.78; 5.7 ± 1.05, p < 0.001, non-parametric ANOVA).

Conclusions

Intracranial surgery was demonstrated to induce an inflammatory reaction within the hippocampus that compromised neurogenesis and impaired normal cognitive processing. Corticectomy had a greater effect than craniotomy alone, indicating a central trigger for hippocampal inflammatory changes. POCD after craniotomy may originate from a central inflammatory response resulting from surgical trauma to the brain parenchyma.

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Acknowledgments

This paper is dedicated to the memory of Dr. Pablo Argibay, a true master for all of us. This work was supported by a grant from “Hospital Italiano de Buenos Aires”.

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Authors and Affiliations

  1. Department of Neurosurgery, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina

    Santiago Hem, Jorge Rasmussen, Pablo Ajler, Claudio Yampolsky & Ezequiel Goldschmidt

  2. Institute of Basic Sciences and Experimental Medicine, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina

    Romina Albite, Monica Loresi & Ezequiel Goldschmidt

  3. Department of Neurosurgery, University of Pittsburgh Medical Center, 200 Lothrop Street, Suite B-400, Pittsburgh, PA, 15213, USA

    Joseph D. Chabot, Peter C. Gerszten & Ezequiel Goldschmidt

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  1. Santiago Hem
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Correspondence to Ezequiel Goldschmidt.

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Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted. This article does not contain any studies with human participants performed by any of the authors.

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This work was supported by a grant from “Hospital Italiano de Buenos Aires”.

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The authors declare that they have no conflicts of interest.

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Hem, S., Albite, R., Loresi, M. et al. Pathological changes of the hippocampus and cognitive dysfunction following frontal lobe surgery in a rat model. Acta Neurochir 158, 2163–2171 (2016). https://doi.org/10.1007/s00701-016-2938-6

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  • DOI: https://doi.org/10.1007/s00701-016-2938-6

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