Minocycline Attenuates Cognitive Impairment Induced by Isoflurane Anesthesia in Aged Rats

Feijuan Kong,Huishun Lu,Shuping Chen,Wenwen Hu,Leilei Ma,Yuan Cheng,Honghai Zhang,Brian Christie

doi:10.1371/journal.pone.0061385

Abstract

Postoperative cognitive dysfunction (POCD) is a clinical phenomenon characterized by cognitive deficits in patients after anesthesia and surgery, especially in geriatric surgical patients. Although it has been documented that isoflurane exposure impaired cognitive function in several aged animal models, there are few clinical interventions and treatments available to prevent this disorder. Minocycline has been well established to exert neuroprotective effects in various experimental animal models and neurodegenerative diseases. Therefore, we hypothesized that pretreatment with minocycline attenuates isoflurane-induced cognitive decline in aged rats. In the present study, twenty-month-old rats were administered minocycline or an equal volume of saline by intraperitoneal injection 12 h before exposure to isoflurane. Then the rats were exposed to 1.3% isoflurane for 4 h. Two weeks later, spatial learning and memory of the rats were examined using the Morris Water Maze. We found that pretreatment with minocycline mitigated isoflurane-induced cognitive deficits and suppressed the isoflurane-induced excessive release of IL-1β and caspase-3 in the hippocampal CA1 region at 4 h after isoflurane exposure, as well as the number of TUNEL-positive nuclei. In addition, minocycline treatment also prevented the changes of synaptic ultrastructure in the hippocampal CA1 region induced by isoflurane. In conclusion, pretreatment with minocycline attenuated isoflurane-induced cognitive impairment in aged rats.

Highlights

Postoperative cognitive dysfunction (POCD), a major clinical issue, is described as cognitive deficits in memory and concentration after anesthesia and surgery, especially in geriatric surgical patients
The current clinical data does not provide a strong link between anesthesia and cognitive impairment, a number of preclinical studies demonstrate that exposure to volatile anesthetics causes cognitive impairment for days or weeks in aged animals [10,11,12,13,14]
Minocycline treatment suppressed the excessive release of IL1b and neuronal apoptosis and prevented the impairment of synaptic ultrastructure in the hippocampal CA1 region induced by isoflurane

Summary

Introduction

Postoperative cognitive dysfunction (POCD), a major clinical issue, is described as cognitive deficits in memory and concentration after anesthesia and surgery, especially in geriatric surgical patients. The current clinical data does not provide a strong link between anesthesia and cognitive impairment, a number of preclinical studies demonstrate that exposure to volatile anesthetics causes cognitive impairment for days or weeks in aged animals [10,11,12,13,14]. These observations raise concerns about the potentially deleterious effects of general anesthesia in elderly patients

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