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Published on: August 15, 2012
Maprotiline ameliorates isoflurane-induced microglial activation via regulating triggering receptor expressed in
Rui Hu1, Yongguan He2, Zhigang Chen3
1Department of Anesthesiology, Affiliated Hospital of Guilin Medical College, Guilin, China.
Abstract:
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.
Insights
Maprotiline protects against isoflurane-induced neurotoxicity by reducing microglial activation, oxidative stress, and inflammation. This antidepressant drug may serve as a therapeutic agent for preventing isoflurane-related brain damage.
Area of Science:
- Neuroscience
- Pharmacology
- Toxicology
Background:
- Isoflurane anesthesia can cause neurotoxicity, characterized by microglial activation and subsequent inflammation.
- Maprotiline, an antidepressant, exhibits anti-inflammatory properties, but its protective effects against isoflurane-induced microglial injury are unexplored.
Purpose of the Study:
- To investigate the potential neuroprotective effects of maprotiline against isoflurane-induced microglial damage.
- To elucidate the underlying mechanisms, including oxidative stress, inflammation, and the role of TREM2.
Main Methods:
- BV2 microglial cells were exposed to isoflurane, with or without maprotiline treatment.
- Cell viability, lactate dehydrogenase (LDH) release, reactive oxygen species (ROS) production, and superoxide dismutase (SOD) activity were assessed.
- Inflammatory markers (TNF-α, IL-1β, COX-2, PGE2), microglial activation marker (Iba1), and TREM2 expression were quantified.
- TREM2 was knocked down to assess its role in maprotiline's protective effects.
Main Results:
- Maprotiline improved cell viability and reduced LDH release in isoflurane-treated BV2 cells.
- Maprotiline inhibited isoflurane-induced oxidative stress (decreased ROS, increased SOD activity).
- Maprotiline suppressed inflammatory markers and Iba1 expression, while restoring TREM2 levels.
- TREM2 knockdown abolished maprotiline's protective effects.
Conclusions:
- Maprotiline demonstrates significant protective effects against isoflurane-induced microglial injury.
- These benefits are mediated through the inhibition of oxidative stress, inflammation, and microglial activation, involving TREM2 regulation.
- Maprotiline shows promise as a therapeutic agent for mitigating isoflurane neurotoxicity.
