Pregabalin can prevent, but not treat, cognitive dysfunction following abdominal surgery in aged rats

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• 作者：Takashi Kawano^a ; ^{takashika@kochi-u.ac.jp" class="auth_mail" title="E-mail the corresponding author} ; Satoru Eguchi^b ; Hideki Iwata^a ; Daiki Yamanaka^a ; Hiroki Tateiwa^a ; Fabricio M. Locatelli^a ; Masataka Yokoyama^a
• 关键词：Post-operative cognitive dysfunction ; Neuroinflammation ; Microglia
• 刊名：Life Sciences
• 出版年：2016
• 出版时间：1 March 2016
• 年：2016
• 卷：148
• 期：Complete
• 页码：211-219
• 全文大小：1177 K

文摘

The present study aimed to explore the preventive or therapeutic effect of peri-operative pregabalin treatment on the memory deficits and related hippocampal inflammation following surgery in aged rats.

Main methods

Aged rats underwent abdominal or sham surgery, and were then divided into 2 groups, either early or late pregabalin treatment. Fourteen days after surgery, the cognitive function was assessed using novel object recognition test, followed by measurement of hippocampal cytokines and voltage-dependent calcium channel α2δ subunit (CACNA2D1). The parabiotic experiments determined whether the humoral or neuronal pathway was involved in the neuroinflammation development following the abdominal surgery. The effects of pregabalin on LPS-induced cytokine release from hippocampal microglia were also evaluated.

Key findings

Early pregabalin treatment, which was administered pre-operatively and continued for 3 or 7 days after surgery, prevented memory deficits and decreased hippocampal pro-inflammatory cytokine levels. In contrast, no beneficial effects were observed when pregabalin was administered late in the post-operative period. The hippocampal levels of CACNA2D1 did not change under any experimental condition. The data from the cross-circulation (parabiosis) experiments indicated that abdominal surgery may induce neuroinflammation via a neural transmission pathway from the periphery to the brain. The ex vivo experiments further demonstrated that pregabalin had no effect on LPS-induced cytokines release from hippocampal microglia.

Significance

Our findings highlight reveal that peri-operative pregabalin treatment during the early post-operative period can prevent neuroinflammation and memory deficits after surgery. It is likely this occurs through a peripheral and central neuro-immune interaction rather than through direct anti-inflammatory effects.