Abstract

Occurrence of postoperative cognitive dysfunction (POCD) is age-dependent and heterogenous. Factors deciding the occurrence of POCD in patients of the same age undergone same surgeries remain unclear. Here we investigated the effects of pre-existing weakness on the occurrence of POCD in mice of the same age. Pre-existing weakness of mice was induced by intraperitoneal injection of lipopolysaccharide (8mg/kg) and was evaluated by physical frailty index (by open field test), neuroinflammation level (by Iba1 immunostaining and inflammatory factors TNF-α and IL-1β), and neuronal activity (by p-CREB immunostaining). POCD was induced by partial hepatolobectomy and was evaluated by puzzle box test and Morris water maze test. The brains were collected to detect the levels of neuroinflammation, synaptophysin and NMDA receptor subunits NR2A, NR2B and NR1 (by western blot), and oxidative stress (by Dihydroethidium). Compared to the normal adult mice of the same age, LPS pretreated mice had increased physical frailty index, higher levels of neuroinflammation, and lower neuronal activity. Partial hepatolobectomy induced obvious impairments in executive function, learning and memory in LPS pretreated mice after surgery, but not in normal mice of the same age. Partial hepatolobectomy also induced heightened neuroinflammation, obvious loss of NMDA receptor subunits, strong oxidative stress in LPS pretreated mice on the 1st and 3rd postoperative day. However, the POCD-associated pathological changes didn’t occur in normal mice of the same age after surgery. These results suggest that pre-existing weakness is critical for the occurrence of POCD in mice of the same age.

Highlights

  • Postoperative cognitive dysfunction (POCD), a common postoperative complication in the elderly patients, is characterized by subtle deficits in one or more discrete domains of cognition, e.g. attention, concentration, executive function, verbal memory, visuospatial abstraction and psychomotor speed [1,2]

  • Weak individuals were characterized by increased physical frailty index[24], structural and functional changes in brain including increased neuroinflammation, primed microglia[38] and low neuronal activity[25,26]

  • P-CREB is a common marker of neuronal activity, and its expression decreases in an age-dependent manner

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Summary

Introduction

Postoperative cognitive dysfunction (POCD), a common postoperative complication in the elderly patients, is characterized by subtle deficits in one or more discrete domains of cognition, e.g. attention, concentration, executive function, verbal memory, visuospatial abstraction and psychomotor speed [1,2]. Pre-existing weakness is critical for the occurrence of postoperative cognitive dysfunction after surgery, and 10% to 15% of elderly patients three month after surgery[3,4]. Further studies have shown that, for elderly patients of the same age and undergone same surgeries, POCD more commonly occurred in patients who exhibited preoperative co-morbidities, e.g. pre-existing cognitive impairment[17], decreased hippocampal volume[18], reduced blood flow in the left middle cerebral artery[19], etc. Our data showed that pre-existing weakness obviously affected the occurrence of POCD and the related pathological changes

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