High doses of minocycline may induce delayed activation of microglia in aged rats and thus cannot prevent postoperative cognitive dysfunction.
Objective Postoperative cognitive dysfunction (POCD) is common after surgery in elderly patients and is associated with high morbidity. The molecular mechanisms responsible for POCD are unknown. Minocycline, an inhibitor of microglial activation, may be useful in treating and preventing POCD. We explored whether minocycline can inhibit microglial activation and prevent POCD in aged rats as a surgery model. Methods Rats aged 18 to 20 months were randomly allocated to the following groups: naïve, abdominal surgery alone, or minocycline injection before abdominal surgery. Hippocampal cytokine mRNA levels were measured at 3 hours, 1 day, 3 days, and 7 days after surgery, and microglial activation was measured at 3 hours and 7 days after surgery. Memory was assessed using the Morris water maze test. Results Surgery resulted in severe cognitive impairment in aged rats and induced a significant neuroinflammatory response and microglial activation. The use of minocycline can prevent microglial activation after surgery, but delayed microglial activation may occur. The use of minocycline may further impair memory after surgery. Conclusion Minocycline can restrain microglial activation and restrict the inflammatory response in the hippocampus early after surgery, but it may induce delayed microglial activation and cannot prevent POCD in aged rats.
['Li|Wenyao|W|', 'Chai|Qing|Q|', 'Zhang|Hongwei|H|', 'Ma|Jing|J|', 'Xu|Chengfen|C|', 'Dong|Jifu|J|', 'Wei|Xianghua|X|', 'Wang|Zhiyi|Z|', 'Zhang|Kexian|K|http://orcid.org/0000-0003-3213-9114']
D000375:Aging D000818:Animals D060825:Cognitive Dysfunction D004305:Dose-Response Relationship, Drug D006624:Hippocampus D053583:Interleukin-1beta D008570:Memory, Short-Term D017628:Microglia D008911:Minocycline D011183:Postoperative Complications D012333:RNA, Messenger D017207:Rats, Sprague-Dawley D014409:Tumor Necrosis Factor-alpha
Minocycline microglia aged rat postoperative cognitive dysfunction surgery model inflammation