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Protective Effect of RNase on Unilateral Nephrectomy-Induced Postoperative Cognitive Dysfunction in Aged Mice.

Chen C, Cai J, Zhang S, Gan L, Dong Y, Zhu T, Ma G, Li T, Zhang X, Li Q, Cheng X, Wu C, Yang J, Zuo Y, Liu J - PLoS ONE (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

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.

No MeSH data available.


Related in: MedlinePlus

The schematic outline of the experimental protocol and the timeline of RNase administration.A, Schematic outline of the experimental protocol. B, Timeline of RNase A administration. MWM, Morris water maze; S-S, sham surgery plus placebo; S-P, surgery plus placebo; S-R, surgery plus RNase.
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pone.0134307.g001: The schematic outline of the experimental protocol and the timeline of RNase administration.A, Schematic outline of the experimental protocol. B, Timeline of RNase A administration. MWM, Morris water maze; S-S, sham surgery plus placebo; S-P, surgery plus placebo; S-R, surgery plus RNase.

Mentions: Morris Water Maze (MWM) was chosen for the assessment of learning and memory, one aspect of the cognition [20]. Briefly, the water maze consisted of a round tank (diameter: 120 cm, depth: 40 cm) of water rendered opaque by adding white non-toxic paint, and the water temperature was maintained at 25°C. A platform submersed 1 cm below surface was placed in one quadrant of the tank and maintained in the same position during all trials. Several visual clues were placed around the pool as the mice’s navigational reference points for locating the platform. A video camera in conjunction with the SMART video tracking software (Panlab, Barcelona, Spain) was used for the measurement of swimming speed, latency to escape to the platform, percentage of time spent in the target quadrant and distance swam to the platform. The training session consisted of 3 consecutive trials per day for 7 days before surgery (Fig 1A), during which the mice were placed in the desired start position in the maze facing the tank wall, and allowed to swim freely to the escape platform. Trial time limit is 90 seconds. If the mice did not find the platform within the time limit, they were gently guided to it. The testing session including 3 consecutive trials was performed for 7 days after surgery (Fig 1A). The probe tests with the platform removed were performed on the 3rd or 7th postoperative day. The probe test was 90 seconds in duration, and the percentage of time spent in the quadrant previously containing the submerged platform was recorded.


Protective Effect of RNase on Unilateral Nephrectomy-Induced Postoperative Cognitive Dysfunction in Aged Mice.

Chen C, Cai J, Zhang S, Gan L, Dong Y, Zhu T, Ma G, Li T, Zhang X, Li Q, Cheng X, Wu C, Yang J, Zuo Y, Liu J - PLoS ONE (2015)

The schematic outline of the experimental protocol and the timeline of RNase administration.A, Schematic outline of the experimental protocol. B, Timeline of RNase A administration. MWM, Morris water maze; S-S, sham surgery plus placebo; S-P, surgery plus placebo; S-R, surgery plus RNase.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4520469&req=5

pone.0134307.g001: The schematic outline of the experimental protocol and the timeline of RNase administration.A, Schematic outline of the experimental protocol. B, Timeline of RNase A administration. MWM, Morris water maze; S-S, sham surgery plus placebo; S-P, surgery plus placebo; S-R, surgery plus RNase.
Mentions: Morris Water Maze (MWM) was chosen for the assessment of learning and memory, one aspect of the cognition [20]. Briefly, the water maze consisted of a round tank (diameter: 120 cm, depth: 40 cm) of water rendered opaque by adding white non-toxic paint, and the water temperature was maintained at 25°C. A platform submersed 1 cm below surface was placed in one quadrant of the tank and maintained in the same position during all trials. Several visual clues were placed around the pool as the mice’s navigational reference points for locating the platform. A video camera in conjunction with the SMART video tracking software (Panlab, Barcelona, Spain) was used for the measurement of swimming speed, latency to escape to the platform, percentage of time spent in the target quadrant and distance swam to the platform. The training session consisted of 3 consecutive trials per day for 7 days before surgery (Fig 1A), during which the mice were placed in the desired start position in the maze facing the tank wall, and allowed to swim freely to the escape platform. Trial time limit is 90 seconds. If the mice did not find the platform within the time limit, they were gently guided to it. The testing session including 3 consecutive trials was performed for 7 days after surgery (Fig 1A). The probe tests with the platform removed were performed on the 3rd or 7th postoperative day. The probe test was 90 seconds in duration, and the percentage of time spent in the quadrant previously containing the submerged platform was recorded.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

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.

No MeSH data available.


Related in: MedlinePlus