Abstract
The study was performed to investigate the effect of combination therapy with melatonin and dexamethasone (DEX) on brain injury in intracerebral hemorrhage (ICH) model in rats. Compared to the control group, combination therapy group with melatonin (10 mg/kg) and DEX (0.025 mg/kg) significantly reduced the degree of (1) brain edema, (2) the permeability of blood brain barrier (measured by Evans blue), (3) Oxidative stress (evaluated by malondialdehyde assay), (4) cytokines expression (tumor necrosis factor-alpha and interleukin-1beta), and (5) apoptosis (measured by Bax and Bcl-2 expression). In addition, we have also clearly demonstrated that the combination therapy significantly ameliorated neurologic scores. Taken together, our results clearly indicated for the first time that strategies targeting multiple proinflammatory pathways may be more effective than a single effector molecule for the treatment of ICH.
MeSH terms
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Analysis of Variance
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Animals
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Apoptosis / drug effects*
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Blood-Brain Barrier / drug effects
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Blood-Brain Barrier / metabolism*
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Blotting, Western
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Body Water / metabolism
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Brain / metabolism
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Brain Edema / drug therapy
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Brain Edema / metabolism*
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Cerebral Hemorrhage / drug therapy*
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Cerebral Hemorrhage / metabolism
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Cerebral Hemorrhage / physiopathology
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Dexamethasone / administration & dosage*
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Drug Therapy, Combination
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Enzyme-Linked Immunosorbent Assay
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Interleukin-1beta / metabolism
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Male
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Melatonin / administration & dosage*
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Neurologic Examination
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Oxidative Stress / drug effects
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Permeability
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Peroxidase / metabolism
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Rats
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Rats, Wistar
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Statistics, Nonparametric
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Time Factors
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Tumor Necrosis Factor-alpha / metabolism
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bcl-2-Associated X Protein / metabolism
Substances
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Bax protein, rat
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Interleukin-1beta
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Proto-Oncogene Proteins c-bcl-2
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Tumor Necrosis Factor-alpha
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bcl-2-Associated X Protein
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Dexamethasone
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Peroxidase
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Melatonin