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Open AccessArticle

Nrf2 Plays an Essential Role in Long-Term Brain Damage and Neuroprotection of Korean Red Ginseng in a Permanent Cerebral Ischemia Model

1
Department of Anesthesiology, Center for Translational Research in Neurodegenerative Disease and McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA
2
Departments of Neurology, Psychiatry, Pharmaceutics, and Neuroscience, University of Florida, Gainesville, FL 32610, USA
*
Author to whom correspondence should be addressed.
Antioxidants 2019, 8(8), 273; https://doi.org/10.3390/antiox8080273
Received: 26 June 2019 / Revised: 30 July 2019 / Accepted: 30 July 2019 / Published: 3 August 2019
(This article belongs to the Special Issue Oxidative and Nitrosative Stress in Astrocytes)
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Abstract

Cerebral ischemia is a devastating disease with a high incidence of death and disability; however, effective therapeutics remain limited. The transcriptional factor Nrf2 has been shown to play a pivotal role in the endogenous defense against brain oxidative stress and inflammation and therefore represents a promising target for stroke intervention. However, the long-term effects of Nrf2 and the standardized Korean red ginseng (ginseng), a potent Nrf2 natural inducer, on permanent cerebral ischemic damage have not yet been reported. Wildtype (WT) and Nrf2−/− adult mice were pretreated with either vehicle or ginseng and were subjected to permanent distal middle cerebral artery occlusion (pdMCAO). The infarct volume, the reactive astrocytes and microglia, and the water regulatory protein aquaporin 4 (AQP4) were examined at 28 days after stroke. When compared with the WT matched controls, the Nrf2 disruption significantly enlarged the infarct volume (40.4 ± 10.1%) and exacerbated the progression of reactive gliosis and AQP4 protein levels after pdMCAO. In contrast, ginseng significantly reduced the infarct volume and attenuated the reactive gliosis and AQP4 in the ischemic WT mice (47.3 ± 6.9%), but not in the Nrf2−/− mice (25.5 ± 5.6%). In conclusion, Nrf2 plays an important role in the long-term recovery of permanent cerebral ischemic damage and the neuroprotection of ginseng. View Full-Text
Keywords: aquaporin 4; astrocyte; MCAO; microglia; neuroprotection; panax ginseng; reactive gliosis; recovery; stroke aquaporin 4; astrocyte; MCAO; microglia; neuroprotection; panax ginseng; reactive gliosis; recovery; stroke
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Liu, L.; Kelly, M.G.; Wierzbicki, E.L.; Escober-Nario, I.C.; Vollmer, M.K.; Doré, S. Nrf2 Plays an Essential Role in Long-Term Brain Damage and Neuroprotection of Korean Red Ginseng in a Permanent Cerebral Ischemia Model. Antioxidants 2019, 8, 273.

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