Abstract
Postoperative cognitive dysfunction (POCD) is a common complication after surgery, especially for elderly patients. Administration of RNase has been reported to exhibit neuroprotective effects in acute stroke. However, the potential role of RNase on POCD is unknown. Therefore, we sought to investigate whether RNase treatment could mitigate unilateral nephrectomy induced-cognitive deficit in aged mice. In the present study, twelve-month-old mice were administered RNase or an equal amount of normal saline perioperatively. All mice underwent Morris Water Maze (MWM) training 3 times per day for 7 days to acclimatize them to the water maze before surgical operation, and testing on days 1, 3 and 7 after surgery. We found that perioperative administration of RNase: 1) attenuated unilateral nephrectomy-induced cognitive impairment at day 3 after surgery; 2) reduced the hippocampal cytokines mRNA production and serum cytokines protein production at day 1 and day 7 (for MCP-1) after surgery, and; 3) inhibited hippocampal apoptosis as indicated by cleaved caspase-3 western blot and TUNEL staining at day 1 after surgery. In addition, a trend decrease of total serum RNA levels was detected in the RNase treated group after surgery compared with the untreated group. Further, our protocol of RNase administration had no impact on the arterial blood gas analysis right after surgery, kidney function and mortality rate at the observed days postoperatively. In conclusion, perioperative RNase treatment attenuated unilateral nephrectomy-induced cognitive impairment in aged mice.
Highlights
Postoperative cognitive dysfunction (POCD) is a common complication after surgery, especially in elderly patients [1, 2]
Assessment of hippocampal-dependent learning and memory by Morris Water Maze (MWM) in all treatment groups at day 3 postoperatively demonstrated a statistically significant reduction in memory retrieval in surgery plus placebo (S-P) group compared to the surgery plus placebo (S-S) group, as evidenced by escape latency, path length, and percentage of time spent in target quadrant respectively (Fig 2A–2C), suggesting that unilateral nephrectomy induced a significant cognitive impairment in aged mice, emulating POCD
RNase treatment led to significantly enhanced cognitive function, compared with untreated surgical group, as demonstrated by escape latency (23.01 ± 5.15 vs. 43.67 ± 7.23, #P< 0.05) (Fig 2A), path length (333.20 ± 60.60 vs. 636.33 ± 89.72, #P
Summary
Postoperative cognitive dysfunction (POCD) is a common complication after surgery, especially in elderly patients [1, 2]. RNase Treatment and POCD following either cardiac or non-cardiac surgery, which is associated with poor health outcomes of the patients [3, 4]. The reported incidence of early POCD varies in different studies, with the highest around 80% in the first postoperative week [5], and lowest about 17% at one month after surgery [6]. There is growing evidence that systemic inflammation can induce exacerbation and progression of inflammatory responses or damage in the central nervous system (CNS) [10, 11].
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