Title: TR exerts neuroprotective effects against acute ischemic injury via inhibiting oxidative stress


Authors: Huan-Yu Ni1,2, Yi-Xuan Song1,2, Hai-Yin Wu1,2, Lei Chang1,2, Chun-Xia Luo1,2, Dong-Ya Zhu1,2,3


Institutions: 1Institution of Stem Cells and Neuroregeneration; 2Department of Pharmacology, School of Pharmacy; 3The Key Laboratory of Precision Medicine of Cardiovascular Disease, Nanjing Medical University, Nanjing, Jiangsu 211166, China


Abstract: Oxidative stress plays an indispensable role in the pathologenesis of cerebral ischemia. Inhibiting oxidative stress has been considered as an effective approach for stroke treatment. Edaravone, a free radical scavenger, has been shown to prevent cerebral ischemic injury. However, the clinical efficacy of edaravone is limited because it has a low scavenging activity for superoxide anions (O2$–). Here, we report that TR, a novel small-molecule compound structurally related to edaravone, showed a stronger inhibitory effect on oxidative stress in vitro. In vivo, TR reversed transient middle cerebral artery occlusion-induced dysfunctions of superoxide dismutases and malondialdehyde, two proteins crucial for oxidative stress, suggesting a strengthened antioxidant system. Moreover, TR decreased blood brain barrier permeability. Then, we found that TR had a stronger neuroprotective effect than edaravone. More importantly, TR treatment decreased not only infarct size and neurological deficits in the acute phase but also modified neurological severity score and escape latency in Morris water maze task in the delayed period, indicating enhanced neuroprotection, sensorimotor function and spatial memory. Together, these findings suggest that TR could be a preferable option for stroke treatment.


Keywords: neuroprotection, oxidative stress, scavenging activity, sensorimotor function, spatial memory, stroke


Full Text: JBR-2018-0014 pre-proof.pdf


J Biomed Res published on 20 April 2018, https://doi.org/10.7555/JBR.32.20180014