Abstract
Post-operative cognitive dysfunction (POCD) can be a serious surgical complication, and patients undergoing cardiac procedures are at particular risk for POCD. This study examined the effect of blocking neuroinflammation on behavioral and neurogenic deficits produced in a rat model of cardiopulmonary bypass (CPB). Minocycline, a drug with established anti-inflammatory activity, or saline was administered daily for 30 days post-CPB. Treatment with minocycline reduced the number of activated microglia/macrophages observed in the dentate gyrus of the hippocampus at 6 months post-CPB, consistent with an anti-inflammatory action in this CPB model. Behavioral testing was conducted at 6 months post-CPB utilizing a win-shift task on an 8-arm radial maze. Minocycline-treated animals performed significantly better than saline-treated animals on this task after CPB. In addition, the CPB-induced reduction in adult neurogenesis was attenuated in the minocycline-treated animals. Together, these findings indicate that suppressing neuroinflammation during the early post-surgical phase can limit long-term deficits in both behavioral and neurogenic outcomes after CPB.
Highlights
Post-operative cognitive dysfunction (POCD) can complicate surgical outcomes, and is a particular risk for cardiac patients (e.g., Priest et al, 1957; Rasmussen, 2006; Selnes et al, 2006; Fink et al, 2015; Berger et al, 2018)
Minocycline treatment during the first month post-cardiopulmonary bypass (CPB) reduced the amount of activated microglia/macrophages observed in the hippocampus at 6 months post-CPB, a finding that is consistent with the known anti-inflammatory actions of this compound (Figure 1)
The number of DCX-positive cells was significantly higher in the CPB + Minocycline group as compared to the CPB + Saline group, a finding that is consistent with greater ongoing neurogenesis in the treated group
Summary
Post-operative cognitive dysfunction (POCD) can complicate surgical outcomes, and is a particular risk for cardiac patients (e.g., Priest et al, 1957; Rasmussen, 2006; Selnes et al, 2006; Fink et al, 2015; Berger et al, 2018). Systemic administration of an antineuroinflammatory drug, minocycline, can restore neurogenesis (Ekdahl et al, 2003), raising the possibility that attenuating post-operative neuroinflammation might mitigate cognitive deficits. The potential efficacy of anti-inflammatory medication in POCD was supported by a recent meta-analysis of clinical data (Jorna et al, 2020). Together, these findings suggest that neuroinflammation plays an important role in POCD, and that anti-inflammatory treatment may be an effective remedy
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