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Post-Injury Administration of Tert-butylhydroquinone Attenuates Acute Neurological Injury After Intracerebral Hemorrhage in Mice

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Abstract

Intracerebral hemorrhage (ICH) is a severe form of stroke with substantial public health impact. Notably, there is no effective treatment for ICH. Given the role of transcription factor Nrf2 (NF-E2-related factor 2) in antioxidant signaling, herein, we tested the efficacy of tert-butylhydroquinone (TBHQ), a selective inducer of Nrf2 in a preclinical model of ICH. Male CD1 mice were subjected to experimental intracerebral hemorrhage and administered intraperitoneally with TBHQ. The administration of TBHQ enhanced the DNA-binding activity of Nrf2 in the brain and reduced oxidative brain damage in comparison to vehicle-treated ICH. In addition, TBHQ treatment reduced microglial activation with concomitant reduction in the release of proinflammatory cytokine interleukin-1β (IL-1 β). Furthermore, TBHQ treatment attenuated neurodegeneration and improved neurological outcomes after ICH. Altogether, the data demonstrate the efficacy of post-injury administration of TBHQ in attenuating acute neurological injury after ICH.

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Acknowledgments

This work was supported by grant from the American Heart Association (14SDG18730034) to SSR. Authors would like to acknowledge Frederick Bonsack for his technical assistance.

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Correspondence to Sangeetha Sukumari-Ramesh.

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Sukumari-Ramesh, S., Alleyne, C.H. Post-Injury Administration of Tert-butylhydroquinone Attenuates Acute Neurological Injury After Intracerebral Hemorrhage in Mice. J Mol Neurosci 58, 525–531 (2016). https://doi.org/10.1007/s12031-016-0722-y

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  • DOI: https://doi.org/10.1007/s12031-016-0722-y

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