Pathological changes of the hippocampus and cognitive dysfunction following frontal lobe surgery in a rat model
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.
KeywordsCerebral surgery Hippocampus Inflammation Postoperative cognitive dysfunction
|Funder Name||Grant Number||Funding Note|
|Hospital Italiano de Buenos Aires|