Pre-existing weakness is critical for the occurrence of postoperative cognitive dysfunction in mice of the same age

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.

Rapamycin improves sevoflurane‑induced cognitive dysfunction in aged rats by mediating autophagy through the TLR4/MyD88/NF‑κB signaling pathway

“…POCD is mainly manifested as postoperative mental disorder, anxiety, personality changes and impaired memory (19). Some studies have revealed that age was an independent risk factor for POCD (20,21). The incidence of POCD was as high as 25% within 1 week after non-cardiac surgery in elderly patients older than 60 years of age, and the symptoms of 10% of the patients lasted until three months after surgery (22).…”

Inhibiting RIPK1 Limits Neuroinflammation and Alleviates Postoperative Cognitive Impairments in D-Galactose-Induced Aged Mice

“…Anesthesia and left partial hepatectomy was conducted as described earlier (Tang et al, 2017 ). The mice were anesthetized with inhalation sevoflurane.…”

“…The photographs were captured under a microscope (Nikon, Tokyo, Japan) and analyzed. Based on the Iba1 staining, the percentage of activated microglia in dentate gyrus was counted and analyzed as described by Tang et al ( 2017 ).…”

Characterization of DNA hydroxymethylation in the hypothalamus of elderly mice with post‑operative cognitive dysfunction

“…During the 5 min the mice spent in the box, their average distance travelled, total grid crossings, distance travelled around the central region and duration spent in the central region were recorded. Both an escape period of <90 sec after the 7th day of sevoflurane treatment and an open field score of <25% were considered as cognitive damage consistent with a POCD model (26,27).…”