Minocycline attenuates post-operative cognitive impairment in aged mice by inhibiting microglia activation.

Hui‐Lin Wang,Zhang‐Gang Xue,Qing‐Wu Liao,Hua Liu,Hao Fang

doi:10.1111/jcmm.12854

Abstract

Although it is known that isoflurane exposure or surgery leads to post‐operative cognitive dysfunction in aged rodents, there are few clinical interventions and treatments available to prevent this disorder. Minocycline (MINO) produces neuroprotection from several neurodegenerative diseases and various experimental animal models. Therefore, we set out to investigate the effects of MINO pre‐treatment on isoflurane or surgery induced cognitive impairment in aged mice by assessing the hippocampal‐dependent spatial memory performance using the Morris water maze task. Hippocampal tissues were isolated from mice and evaluated by Western blot analysis, immunofluorescence procedures and protein array system. Our results elucidate that MINO down‐regulated the isoflurane‐induced and surgery‐induced enhancement in the protein levels of pro‐inflammatory cytokine tumour necrosis factor alpha, interleukin (IL)‐1β, interferon‐γ and microglia marker Iba‐1, and up‐regulated protein levels of the anti‐inflammatory cytokine IL‐4 and IL‐10. These findings suggest that pre‐treatment with MINO attenuated isoflurane or surgery induced cognitive impairment by inhibiting the overactivation of microglia in aged mice.

Highlights

Post-operative cognitive dysfunction (POCD), a major clinical issue, is an impairment of recent memory, concentration, language comprehension and social integration
We detected anti-inflammatory cytokine IL-4 and IL-10 protein levels at a series of time-points after anaesthesia or surgery, which were respectively shown in Figure 5A and B
Our recent research show that the pathway of microglia activation and pro-inflammatory cytokine release contributed to the neurotoxicity and impairment of learning and memory induced by isoflurane or surgery [29]

Summary

Introduction

Post-operative cognitive dysfunction (POCD), a major clinical issue, is an impairment of recent memory, concentration, language comprehension and social integration. It is reported that at the time of discharge from the hospital, 41.4% of elderly patients (60 years or older) were subjected to POCD after non-cardiac surgery [1]. Postoperative cognitive dysfunction diminishes the quality of the patient’s life and adds cost to hospitalization and out-of-hospital care. Postoperative cognitive dysfunction has been associated with an increase in surgical morbidity and mortality. Its avoidance and treatment represents one of the greatest challenges for the perioperative physician dealing with an elderly surgical population [2, 3].

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Results

Conclusion