High doses of minocycline may induce delayed activation of microglia in aged rats and thus cannot prevent postoperative cognitive dysfunction

Abstract

ObjectivePostoperative 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.MethodsRats 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.ResultsSurgery 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.ConclusionMinocycline 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.

Muscle Injury Induces Postoperative Cognitive Dysfunction

“…In a murine model, it was demonstrated that depleting microglial cells prevented both hippocampal inflammation and cognitive decline after tibial fracture 21 . Pivotal role of microglia was also shown in a rat model of POCD using minocycline to inhibit microglial activation 41 . Surprisingly in this model, the microglial activation was delayed and worsened the cognitive decline after laparotomy in aged rats.…”

Dexmedetomidine reduces hippocampal microglia inflammatory response induced by surgical injury through inhibiting NLRP3

“…Li et al. 14 found that rats which received laparotomy presented prolonger escape latency during morris water maze test. Meanwhile, their space exploration and number of crossing platform decreased significantly after laparotomy.…”

“…Li et al 14 . found that rats which received laparotomy presented prolonger escape latency during morris water maze test.…”

Intra-CA1 Administration of Minocycline Alters the Expression of Inflammation-Related Genes in Hippocampus of CCI Rats

“…A low dose of minocycline (25 mg/kg) showed protective effects, with reduced retinal ganglion cell loss and microglial activation, while a high dose of minocycline (100 mg/kg) showed damage effects, with more retinal ganglion cell loss and microglial activation in mice with retinal ischemia-reperfusion injury (Huang et al, 2018). An in vivo experiment from Li et al also showed that intraperitoneal minocycline treatment (45 mg/kg) may induce delayed activation of microglia in aged rats and thus cannot prevent postoperative cognitive dysfunction (Li et al, 2018). For this reason, although our results do not directly investigate the influence and relevant mechanism of high doses of minocycline (10 and 15 μg/μl) on the neuronal excitability or synaptic strength, the present study suggests the possibility that a high dose of minocycline might regulate cell function in neuronal or non-neuronal cells within the hippocampus of CCI rats.…”