Abstract
Salidroside, a phenylpropanoid glycoside, is the main bioactive component of Rhodiola rosea L. Salidroside has prominent anti-stroke effects in cerebral ischemia/reperfusion models. However, the underlying mechanisms of its actions are poorly understood. This study examined the anti-stroke effects of salidroside in middle cerebral artery occlusion (MCAO)-induced rat model of stroke and its potential mechanisms involving the dopaminergic system. Salidroside administration increased the levels of dopamine (DA), homovanillic acid (HVA), and 3,4-dihydroxyphenylacetic acid (DOPAC) in the ipsilateral striatum after induction of transient ischemia, which were assessed using microdialysis with high-performance liquid chromatography coupled with electrochemical detection (HPLC-ECD). Furthermore, treatment with salidroside ameliorated neurobehavioral impairment, assessed with the modified neurological severity scores (mNSS), the balance beam test, and the foot fault test. Moreover, enzyme-linked immunosorbent assay (ELISA) suggested that MCAO-induced reduction in monoamine oxidase (MAO) was inhibited by salidroside. Immunohistochemical and immunofluorescence analyses revealed high level of tyrosine hydroxylase (TH) in the ipsilateral striatal caudate putamen (CPu) after cerebral ischemia/reperfusion, which could be further elevated by salidroside. In addition, salidroside could reverse the decreased immunoreactivity of TH in the substantia nigra pars compacta (SNpc). These results suggest that the anti-stroke effects of salidroside in MCAO-induced cerebral ischemia/reperfusion may involve the modulation of monoamine metabolism in the striatum and SNpc, which may be related to the function of the dopaminergic system in the rat brain.
Highlights
According to the World Health Organization, stroke is the leading cause of death and permanent disability in adults worldwide (Benjamin et al, 2017; Benjamin et al, 2018)
DA production is regulated by the activity of tyrosine hydroxylase (TH) and aromatic amino acid decarboxylase; DA is metabolized into dihydroxyphenylacetic acid (DOPAC) by monoamine oxidase (MAO)
The administration of salidroside (80 mg/kg) further increased the DA levels (p < 0.01 vs. the vehicle group). These findings suggested that intraperitoneal injection of salidroside can further improve the level of DA
Summary
According to the World Health Organization, stroke is the leading cause of death and permanent disability in adults worldwide (Benjamin et al, 2017; Benjamin et al, 2018). Monoamines may play specific roles in the recovery of sensory, motor, and autonomic function Monoamine neurotransmitters, such as dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA), play an important role in the brain and changes in the concentration are observed in ischemic stroke. DOPAC is metabolized into HVA by catechol-O-methyl transferase (Soriano et al, 1997) In this process, TH is the key enzyme in DA biosynthesis (Calvo et al, 2011). Changes have been observed in vulnerable components of the brain, including the substantia nigra pars (SN), the globus pallidus (Gp), and caudate putamen (CPu) of the striatum (Lin et al, 2010; Shrivastava et al, 2012; Adam et al, 2013). Striatal infarction downregulates TH immunoreactivity following ischemia (Yamada et al, 1996; Li et al, 2016; Mao et al, 2017)
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