Affiliation:
1. Department of Neurology, Stroke Center, The First Hospital of Jilin University, Chang Chun, Jilin, China
2. Department of
Neurology, Neuroscience Research Center, The First Hospital of Jilin University, Chang Chun, Jilin, China
Abstract
Background:
Ischemic stroke is a major cause of death and disability worldwide and
results from inadequate cerebrovascular blood supply; mitochondrial dysfunction plays an essential
role in its pathogenesis. DL-3-n-butylphthalide (NBP) is an effective medicine for ischemic stroke
that reduces cell apoptosis and improves long-term prognosis.
Objective:
Whether and how NBP regulates mitochondria-associated apoptosis in cerebral ischemia-
reperfusion injury remains unclear.
Methods:
Male Sprague Dawley rats were subjected to a middle cerebral artery occlusion (MCAO)
stroke and treated with low (20 mg/kg) or high (80 mg/kg) concentrations of NBP. The Omi/HtrA2
inhibitor UCF-101 was used as a positive control. Cerebral infarction, neuron injury and neuronal
apoptosis were assessed to determine the efficacy of NBP compared to UCF-101. We assessed the
expression of the Omi/HtrA2 signaling pathway by western blotting and tested the mRNA expression
of mitochondrial metabolism-related genes by PCR.
Results:
Compared to the MCAO group, both low and high concentrations of NBP substantially
improved cerebral infarction, neuron injury, and neuronal apoptosis; high concentrations of NBP
were more potent than low concentrations. The expression of proteins of the mitochondrial
Omi/HtrA2 signaling pathway, including Omi/HtrA2, XIAP, PARL, OPA1, CHOP, and ClpP, was
inhibited in the NBP group.
Conclusion:
Overall, early application of NBP attenuated cerebral ischemia-reperfusion injury by
inhibiting mitochondrial Omi/HtrA2-mediated apoptosis in rats. Our study supports a novel neuroprotective
mechanism of NBP, making it a promising therapeutic agent for ischemic stroke.
Publisher
Bentham Science Publishers Ltd.
Subject
Cellular and Molecular Neuroscience,Developmental Neuroscience,Neurology,Neurology (clinical)