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It's neuroprotective effects have been shown against various neurological disorders. Recent research work has demonstrated that PPX exerts neuroprotection through mitochondria. However, the neuromodulator related effects of PPX against traumatic brain injury (TBI) remain unexplored. The present study was, therefore, aimed to explore the mechanism of neuroprotection by PPX against oxidative stress, mitochondrial dysfunction, and neuronal damage following TBI. We hypothesized that the neuroprotection by PPX might involve activation of Nrf2\/HO-1 signaling pathway in TBI-subjected rats. PPX was injected intraperitoneally (0.25 &amp; 1.0 mg\/kg b.wt.) at different time interval post-TBI. Several neurobehavioral parameters were assessed at 48 h post-TBI, and the brain was isolated for molecular and biochemical analysis. The results demonstrated that PPX treatment significantly improved the behavioral deficits, decreased lipid peroxidation rate, increased glutathione level, and decreased the 4-hydroxynonenal protein expression in TBI-subjected rats. PPX also increased the activity of glutathione peroxidase and superoxide dismutase enzymes. In addition, PPX treatment inhibited the mitochondrial ROS production, restored mitochondrial membrane potential, and increased ATP level after TBI. Further, PPX treatment reduced the Bax\/Bcl2 ratio and translocation of Bax to mitochondria and cytochrome-c to cytosol. Finally, PPX treatment greatly accelerated the translocation of Nrf2 to the nucleus and upregulated the HO-1 protein expression. We concluded that the neuroprotective effects of PPX were mediated by activation of Nrf2\/HO-1 signaling pathway following TBI.<\/jats:p>","DOI":"10.1242\/dmm.045021","type":"journal-article","created":{"date-parts":[[2020,6,15]],"date-time":"2020-06-15T13:15:11Z","timestamp":1592226911000},"source":"Crossref","is-referenced-by-count":30,"title":["Nrf2\/HO-1 mediates neuroprotective effects of pramipexole by attenuating oxidative damage and mitochondrial perturbation after traumatic brain injury"],"prefix":"10.1242","author":[{"given":"Mohd.","family":"Salman","sequence":"first","affiliation":[{"name":"Department of Medical Elementology and Toxicology, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi 110062, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heena","family":"Tabassum","sequence":"additional","affiliation":[{"name":"Division of Basic Medical Sciences, Indian Council of Medical Research, Ministry of Health and Family Welfare, Government of India, V. 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