Maprotiline ameliorates isoflurane-induced microglial activation via regulating triggering receptor expressed in myeloid cells 2 (TREM2)

Bioengineered

Rui Hu¹  Yongguan He²  Zhigang Chen³ 

[1] Affiliated Hospital of Guilin Medical College;The Central Hospital of Enshi Tujia and Miao Autonomous Prefectrue, Enshi Tujia and Miao Autonomous Prefecture;wuhanxinzhou District People’s Hospital;

关键词: isoflurane;    maprotiline;    microglial activation;    oxidative stress;    inflammation;    trem2;   

DOI  :  10.1080/21655979.2021.2000740

来源: DOAJ

【 摘 要 】

Isoflurane-induced neurotoxicity has attracted much interest. Recent studies suggest that isoflurane causes microglial activation, resulting in an inflammatory response and microglial insult. Maprotiline is a novel drug that has been licensed as an antidepressant with considerable anti-inflammatory activity. However, it is still unknown whether maprotiline possesses a protective effect against isoflurane-induced microglial insult. Here, we found that maprotiline ameliorated isoflurane-caused reduction in BV2 microglial cell viability and lactate dehydrogenase (LDH) release. Maprotiline mitigated isoflurane-induced oxidative stress by inhibiting reactive oxygen species (ROS) production and increasing superoxide dismutase (SOD) activity. Isoflurane-induced expression and production of inflammatory markers including tumor necrosis factor (TNF-α), interleukin (IL)-1β, cyclooxygenase‐2 (COX-2), and prostaglandin E2 (PGE2) were decreased in maprotiline-treated cells. Maprotiline inhibited the mRNA and protein levels of Iba1, a marker of microglial activation, in isoflurane-induced BV2 cells. Maprotiline treatment restored isoflurane-induced reduction of TREM2 in BV2 microglial cells. In addition, the knockdown of TREM2 abolished the beneficial effects of maprotiline against isoflurane. Collectively, maprotiline exerted protective effects against isoflurane-caused oxidative stress, inflammatory response, and cell injury via regulating TREM2. These findings show that maprotiline prevented the isoflurane-induced microglial activation, indicating that maprotiline might be used as an optimal therapeutic agent for preventing the isoflurane-caused neurotoxicity.

【 授权许可】

Unknown