A novel Nrf2 activator, RS9, attenuates secondary brain injury after intracerebral hemorrhage in sub-acute phase

Brain Research
Tomoki SugiyamaHideaki Hara

Abstract

The poor prognosis of intracranial hemorrhage (ICH) is attributed to secondary brain injury (SBI), which is caused by oxidative stress. Blood components induce reactive oxygen species (ROS) over-production and cause cytotoxicity. We focused on the antioxidant system and investigated nuclear factor-erythroid 2-related factor 2 (Nrf2), which is a transcription factor that controls several antioxidant enzymes. We examined the effects of a novel Nrf2 activator, RS9, on SBI after ICH. ICH was induced by injecting autologous blood collected from the jugular vein (25 µL) into the striatum of mice. RS9 (0.2 mg/kg, i.p.) was administrated 0, 24, and 48 h after the induction of ICH. Using the ICH model, we measured brain edema, neurological function, neuronal damage and antioxidant proteins expression. We then investigated the mechanisms responsible for the effects of RS9 in vitro using the SH-SY5Y cell line. We used zinc protoporphyrin (ZnPP), a heme oxygenase-1 (HO-1) inhibitor, to elucidate the relationship between HO-1 expression and cell death in vitro in a hemin injury model. RS9 decreased brain edema, improved neurological deficits, decreased neuronal damage area and up-regulated HO-1 and superoxide dismutase 1 (SOD) expressions i...Continue Reading

Citations

May 6, 2019·Investigative Ophthalmology & Visual Science·Shinsuke NakamuraMasamitsu Shimazawa
Aug 19, 2020·Naunyn-Schmiedeberg's Archives of Pharmacology·Takahiko ImaiMasamitsu Shimazawa
Aug 25, 2020·Oxidative Medicine and Cellular Longevity·Liangkai ChengCaiyan Wang
Jan 15, 2021·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Takahiko ImaiHideaki Hara
Nov 14, 2020·International Journal of Stroke : Official Journal of the International Stroke Society·Siobhan CrillyPaul R Kasher
Mar 11, 2021·Oxidative Medicine and Cellular Longevity·Zhenjia YaoGaiqing Wang

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