title: Pathological changes of the hippocampus and cognitive dysfunction following frontal lobe surgery in a rat model.
abstract: 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.
authors.affiliation: Department of Neurosurgery, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Santiago
authors.initials: S
authors.lastname: Hem
authors.affiliation: Institute of Basic Sciences and Experimental Medicine, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Romina
authors.initials: R
authors.lastname: Albite
authors.affiliation: Institute of Basic Sciences and Experimental Medicine, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Monica
authors.initials: M
authors.lastname: Loresi
authors.affiliation: Department of Neurosurgery, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Jorge
authors.initials: J
authors.lastname: Rasmussen
authors.affiliation: Department of Neurosurgery, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Pablo
authors.initials: P
authors.lastname: Ajler
authors.affiliation: Department of Neurosurgery, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Claudio
authors.initials: C
authors.lastname: Yampolsky
authors.affiliation: Department of Neurosurgery, University of Pittsburgh Medical Center, 200 Lothrop Street, Suite B-400, Pittsburgh, PA, 15213, USA.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Chabot
authors.affiliation: Department of Neurosurgery, University of Pittsburgh Medical Center, 200 Lothrop Street, Suite B-400, Pittsburgh, PA, 15213, USA.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Gerszten
authors.affiliation: Department of Neurosurgery, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina. goldschmidted@upmc.edu.|Institute of Basic Sciences and Experimental Medicine, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina. goldschmidted@upmc.edu.|Department of Neurosurgery, University of Pittsburgh Medical Center, 200 Lothrop Street, Suite B-400, Pittsburgh, PA, 15213, USA. goldschmidted@upmc.edu.
authors.forename: Ezequiel
authors.initials: E
authors.lastname: Goldschmidt
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D060825:Cognitive Dysfunction / Q000209:etiology*; D000089662:Doublecortin Protein; D005625:Frontal Lobe / Q000601:surgery*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008297:Male; D055495:Neurogenesis; D019635:Neurosurgical Procedures / Q000009:adverse effects*; D011183:Postoperative Complications; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha
keywords: Cerebral surgery; Hippocampus; Inflammation; Postoperative cognitive dysfunction