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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

RNase treatment decreased cytokine expression in the hippocampus and serum after unilateral nephrectomy in aged mice.A, Hippocampal cytokine mRNA. At day 1, day 3 and day 7 after surgery, cytokine mRNA levels were measured using qRT-PCR. B, Serum cytokine protein expression. At day 1, day 3 and day 7 after surgery, cytokine proteins were assayed using Luminex. Data are presented as mean ± SEM (panel A, n = 4 per group; panel B, n = 6 per group). *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001. CXCL1, chemokine (C-X-C mortif) ligand 1; MIP-2, macrophage inflammatory protein-2; MCP-1, monocyte chemotactic protein-1; IL, interleukin; TNF, tumor necrosis factor; S-S, sham surgery plus placebo; S-P, surgery plus placebo; S-R, surgery plus RNase.
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pone.0134307.g004: RNase treatment decreased cytokine expression in the hippocampus and serum after unilateral nephrectomy in aged mice.A, Hippocampal cytokine mRNA. At day 1, day 3 and day 7 after surgery, cytokine mRNA levels were measured using qRT-PCR. B, Serum cytokine protein expression. At day 1, day 3 and day 7 after surgery, cytokine proteins were assayed using Luminex. Data are presented as mean ± SEM (panel A, n = 4 per group; panel B, n = 6 per group). *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001. CXCL1, chemokine (C-X-C mortif) ligand 1; MIP-2, macrophage inflammatory protein-2; MCP-1, monocyte chemotactic protein-1; IL, interleukin; TNF, tumor necrosis factor; S-S, sham surgery plus placebo; S-P, surgery plus placebo; S-R, surgery plus RNase.

Mentions: Unilateral nephrectomy dramatically increased mRNA expression of CXCL1 and MIP-2 in the hippocampus at day 1 in aged mice compared with the sham control. This increase was significantly reduced by perioperative treatment with 3 doses of RNase (Fig 4A, ***P<0.001, ****P<0.0001). For MCP-1 the increase in the S-P group reached significance at day 7 after surgery and was also attenuated by RNase treatment (Fig 4A, *P<0.05, **P<0.01). Serum cytokines protein expression including IL-1β, IL-6, KC, and TNFα were significantly increased in the S-P group compared with the sham control at day 1 after surgery, and the increase was also significantly decreased in the S-R group (Fig 4B, *P<0.05). There was no difference between the S-R group and the S-S group. These results indicate that neuroprotective effect of RNase may be mediated through reducing both peripheral and hippocampus inflammation.


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)

RNase treatment decreased cytokine expression in the hippocampus and serum after unilateral nephrectomy in aged mice.A, Hippocampal cytokine mRNA. At day 1, day 3 and day 7 after surgery, cytokine mRNA levels were measured using qRT-PCR. B, Serum cytokine protein expression. At day 1, day 3 and day 7 after surgery, cytokine proteins were assayed using Luminex. Data are presented as mean ± SEM (panel A, n = 4 per group; panel B, n = 6 per group). *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001. CXCL1, chemokine (C-X-C mortif) ligand 1; MIP-2, macrophage inflammatory protein-2; MCP-1, monocyte chemotactic protein-1; IL, interleukin; TNF, tumor necrosis factor; S-S, sham surgery plus placebo; S-P, surgery plus placebo; S-R, surgery plus RNase.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0134307.g004: RNase treatment decreased cytokine expression in the hippocampus and serum after unilateral nephrectomy in aged mice.A, Hippocampal cytokine mRNA. At day 1, day 3 and day 7 after surgery, cytokine mRNA levels were measured using qRT-PCR. B, Serum cytokine protein expression. At day 1, day 3 and day 7 after surgery, cytokine proteins were assayed using Luminex. Data are presented as mean ± SEM (panel A, n = 4 per group; panel B, n = 6 per group). *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001. CXCL1, chemokine (C-X-C mortif) ligand 1; MIP-2, macrophage inflammatory protein-2; MCP-1, monocyte chemotactic protein-1; IL, interleukin; TNF, tumor necrosis factor; S-S, sham surgery plus placebo; S-P, surgery plus placebo; S-R, surgery plus RNase.
Mentions: Unilateral nephrectomy dramatically increased mRNA expression of CXCL1 and MIP-2 in the hippocampus at day 1 in aged mice compared with the sham control. This increase was significantly reduced by perioperative treatment with 3 doses of RNase (Fig 4A, ***P<0.001, ****P<0.0001). For MCP-1 the increase in the S-P group reached significance at day 7 after surgery and was also attenuated by RNase treatment (Fig 4A, *P<0.05, **P<0.01). Serum cytokines protein expression including IL-1β, IL-6, KC, and TNFα were significantly increased in the S-P group compared with the sham control at day 1 after surgery, and the increase was also significantly decreased in the S-R group (Fig 4B, *P<0.05). There was no difference between the S-R group and the S-S group. These results indicate that neuroprotective effect of RNase may be mediated through reducing both peripheral and hippocampus inflammation.

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