MEK inhibitor trametinib attenuates neuroinflammation and cognitive deficits following traumatic brain injury in mice

Item Type:	Article
Title:	MEK inhibitor trametinib attenuates neuroinflammation and cognitive deficits following traumatic brain injury in mice
Creators Name:	Huang, Y. and Li, Q. and Tian, H. and Yao, X. and Bakina, O. and Zhang, H. and Lei, T. and Hu, F.
Abstract:	Microglia-mediated neuroinflammation is one of the hallmark pathological features following traumatic brain injury (TBI) that contributes to aggravated brain damage and cognitive deficits. These pathologies require novel effective treatments to improve prognosis. Trametinib, a mitogen-activated protein kinase inhibitor approved by the Food and Drug Administration in treating various malignant tumors, has been shown to exert anti-inflammatory effects. The present study demonstrated that TBI mice treated with trametinib exhibited improved cognitive function. Trametinib treatment rescued oligodendrocytes and decreased infiltrating microglial density in the TBI area. Furthermore, this study revealed that ameliorated lipopolysaccharides (LPS) induced inflammatory reaction in microglial cells. Besides, trametinib attenuated inflammation factors expression during the early stages of TBI. In addition, trametinib inhibited LPS-induced microglial chemotactic activity. In conclusion, the results indicate that trametinib efficiently suppresses microglia-induced neuroinflammation and improves cognitive function of TBI mice, providing a potential therapy strategy for TBI patients.
Keywords:	Traumatic Brain Injury, Microglia, Neuroinflammation, MEK/ERK, Trametinib, Animals, Mice
Source:	American Journal of Translational Research
ISSN:	1943-8141
Publisher:	e-Century Publishing Corporation
Volume:	12
Number:	10
Page Range:	6351-6365
Date:	15 October 2020
Official Publication:	http://www.ajtr.org/files/ajtr0113145.pdf
External Fulltext:	View full text on PubMed Central
PubMed:	View item in PubMed

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