Improvement of mitochondrial function mediated the neuroprotective effect of 5-(4-hydroxy-3-dimethoxybenzylidene)-2-thioxo-4-thiazolidinone in rats with cerebral ischemia-reperfusion injuries
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Mingyang Wang1, Lu Feng1, Ji Zheng1, Junya Liu1, Shujie Fan1, Jun Zhao2, Nan Yang1, Yanyong Liu1, Zhanjun Yang2, Caiying Ye1 and Pingping Zuo1
1Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China
2Department of Human Anatomy, Research Laboratory of Human Anatomy, Baotou Medical College, Inner Mongolia, Baotou 014040, China
Yanyong Liu, email: email@example.com
Zhanjun Yang, email: firstname.lastname@example.org
Caiying Ye, email: email@example.com
Keywords: 5-(4-hydroxy-3-dimethoxybenzylidene)-2-thioxo-4-thiazolidinone, neuroprotection, cerebral ischemia reperfusion, mitochondrial function, synaptic activity
Received: December 14, 2016 Accepted: April 25, 2017 Published: May 22, 2017
Deficits in mitochondrial function is a critical inducement in the major pathways that drive neuronal cell death in ischemic process particularly. Drugs target to improve the mitochondrial function may be a feasible therapeutic choice in treatment with ischemic diseases. In the present study, we investigated whether 5-(4-hydroxy-3-dimethoxybenzylidene)-2-thioxo-4-thiazolidinone (RD-1), a compound derived from rhodanine, could protect against ischemic neuronal damage via improving mitochondrial function. We tested the neuroprotective effect of RD-1 both in rats modeled by middle cerebral artery occlusion reperfusion in vivo and in primary cortical neurons subjected to hypoxia/reperfusion injury in vitro. Results showed that treatment with RD-1 for 14 days remarkably reduced infarct size, decreased neurological deficit score and accelerated the recovery of somatosensory function in vivo. Meanwhile, RD-1 also increased the cellular viability after 48 h treatment in vitro. In addition, RD-1 protected the primary cortical neurons against mitochondrial damage as evidenced by stabilizing the mitochondrial membrane potential and reducing the overproduction of reactive oxygen species. Furthermore, hypoxia/reperfusion injury induced damaged mitochondrial axonal transport and consequently neurotransmitter release disorder, which were ameliorated by RD-1 treatment. Besides, RD-1 inhibited the downregulation of proteins related with mitochondrial transport and neurotransmitter release induced by ischemic injury both in vivo and in vitro. The obtained data demonstrated the neuroprotective effect of RD-1 and the involved mechanisms were partially attributed to the improvement in mitochondrial function and the synaptic activity. Our study indicated that RD-1 may be a potential therapeutic drug for the ischemic stroke therapy.
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