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
- 1.Abildstrom H, Rasmussen LS, Rentowl P, Hanning CD, Rasmussen H, Kristensen PA, Moller JT (2000) Cognitive dysfunction 1–2 years after non-cardiac surgery in the elderly. ISPOCD group. International Study of Post-Operative Cognitive Dysfunction. Acta Anaesthesiol Scand 44(10):1246–1251CrossRefPubMedGoogle Scholar
- 3.Biedler A, Juckenhöfel S, Larsen R, Radtke F, Stotz A, Warmann J, Braune E, Dyttkowitz A, Henning F, Strickmann B, Lauven PM (1999) Postoperative cognition disorders in elderly patients. the results of the “International Study of Postoperative Cognitive Dysfunction” ISPOCD 1). Anaesthesist 48(12):884–895CrossRefPubMedGoogle Scholar
- 6.Canet J, Raeder J, Rasmussen LS, Enlund M, Kuipers HM, Hanning CD, Jolles J, Korttila K, Siersma VD, Dodds C, Abildstrom H, Sneyd JR, Vila P, Johnson T, Munoz Corsini L, Silverstein JH, Nielsen IK, Moller JT (2003) Cognitive dysfunction after minor surgery in the elderly. Acta Anaesthesiol Scand 47(10):1204–1210CrossRefPubMedGoogle Scholar
- 10.Chida K, Ogasawara K, Suga Y, Saito H, Kobayashi M, Yoshida K, Otawara Y, Ogawa A (2009) Postoperative cortical neural loss associated with cerebral hyperperfusion and cognitive impairment after carotid endarterectomy 123I-iomazenil SPECT study. Stroke. doi:10.1161/STROKEAHA.108.515775 Google Scholar
- 13.DiPatri AJ, Pham M, Muro K (2009) Late effects of neurosurgery. Cancer Treat. Res, 7–22Google Scholar
- 26.Moller JT, Cluitmans P, Rasmussen LS, Houx P, Rasmussen H, Canet J, Rabbitt P, Jolles J, Larsen K, Hanning CD, Langeron O, Johnson T, Lauven PM, Kristensen PA, Biedler A, Van Beem H, Fraidakis O, Silverstein JH, Beneken JEW, Gravenstein JS (1998) Long-term postoperative cognitive dysfunction in the elderly: ISPOCD1 study. Lancet 351(9106):857–861CrossRefPubMedGoogle Scholar
- 33.Rasmussen LS, Johnson T, Kuipers HM, Kristensen D, Siersma VD, Vila P, Jolles J, Papaioannou A, Abildstrom H, Silverstein JH, Bonal JA, Raeder J, Nielsen IK, Korttila K, Munoz L, Dodds C, Hanning CD, Moller JT (2003) Does anaesthesia cause postoperative cognitive dysfunction? A randomised study of regional versus general anaesthesia in 438 elderly patients. Acta Anaesthesiol Scand 47(3):260–266CrossRefPubMedGoogle Scholar