Open AccessImprovement of mitochondrial function mediated the neuroprotective effect of 5-(4-hydroxy-3-dimethoxybenzylidene)-2-thioxo-4-thiazolidinone in rats with cerebral ischemia-reperfusion injuries
Author(s) -
Mingyang Wang,
Feng Liang,
Jie Zheng,
Junya Liu,
Shujie Fan,
Jun Zhao,
Nan Yang,
Y Liu,
Zhenhua Yang,
Caiying Ye,
Pingping Zuo
Publication year - 2017
Publication title -
oncotarget
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.373
H-Index - 127
ISSN - 1949-2553
DOI - 10.18632/oncotarget.18048
Subject(s) - neuroprotection , medicine , pharmacology , ischemia , in vivo , apoptosis , mitochondrion , anesthesia , neuroscience , chemistry , biology , biochemistry , microbiology and biotechnology
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.