Acta Neurochirurgica

, Volume 158, Issue 11, pp 2163–2171 | Cite as

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

  • Santiago Hem
  • Romina Albite
  • Monica Loresi
  • Jorge Rasmussen
  • Pablo Ajler
  • Claudio Yampolsky
  • Joseph D. Chabot
  • Peter C. Gerszten
  • Ezequiel Goldschmidt
Experimental Research - Brain Injury



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


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.


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).


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.


Cerebral surgery Hippocampus Inflammation Postoperative cognitive dysfunction 



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”.

Compliance with ethical standards

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.


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

Conflict of interest

The authors declare that they have no conflicts of interest.


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Copyright information

© Springer-Verlag Wien 2016

Authors and Affiliations

  • Santiago Hem
    • 1
  • Romina Albite
    • 2
  • Monica Loresi
    • 2
  • Jorge Rasmussen
    • 1
  • Pablo Ajler
    • 1
  • Claudio Yampolsky
    • 1
  • Joseph D. Chabot
    • 3
  • Peter C. Gerszten
    • 3
  • Ezequiel Goldschmidt
    • 1
    • 2
    • 3
  1. 1.Department of NeurosurgeryHospital Italiano de Buenos AiresBuenos AiresArgentina
  2. 2.Institute of Basic Sciences and Experimental MedicineHospital Italiano de Buenos AiresBuenos AiresArgentina
  3. 3.Department of NeurosurgeryUniversity of Pittsburgh Medical CenterPittsburghUSA

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