Abstract
The hypoxic-ischemic encephalopathy caused by peripartum asphyxia is a serious disease in newborn infants, and effective therapies need to be developed to reduce injury-related disorders. We evaluated the effects of NEP1-40 and fasudil on Nogo-A expression in neonatal hypoxic-ischemic brain damage (HIBD) rats. Seven-day-old Wistar rats were randomly divided into control, HIBD, NEP1-40, and fasudil groups. NEP1-40 and fasudil groups were injected intraperitoneally with these compounds. Rat brains at 6, 24, 72 h, and 7 days after HIBD were collected to determine histopathological damage and the expression levels of Nogo-A. Histopathological damage was reduced in NEP1-40 and fasudil groups compared with the untreated HIBD group. The expression of Nogo-A in the HIBD group was significantly higher than that in control, NEP1-40 and fasudil groups at the same times. Compared with the fasudil group, the expression levels of Nogo-A were significantly reduced in the NEP1-40 group. We conclude that NPE1-40 and fasudil have potential for neuroprotective effects in the neonatal rat HIBD model, mediated by inhibiting Nogo-A/ Rho pathways.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / administration & dosage
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1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / analogs & derivatives*
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1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / therapeutic use
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Animals
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Animals, Newborn
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Brain / drug effects*
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Brain / metabolism
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Brain / pathology
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Carotid Arteries / drug effects
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Carotid Arteries / metabolism
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Carotid Arteries / pathology
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Female
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Gene Expression / drug effects
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Hypoxia-Ischemia, Brain / genetics
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Hypoxia-Ischemia, Brain / metabolism
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Hypoxia-Ischemia, Brain / pathology
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Hypoxia-Ischemia, Brain / prevention & control*
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Immunohistochemistry
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In Situ Hybridization
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Injections, Intraperitoneal
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Ligation / methods
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Male
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Myelin Proteins / administration & dosage
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Myelin Proteins / biosynthesis*
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Myelin Proteins / genetics
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Myelin Proteins / therapeutic use*
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Neurons / cytology
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Neurons / drug effects
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Neurons / metabolism
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Neuroprotective Agents / administration & dosage
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Neuroprotective Agents / therapeutic use*
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Nogo Proteins
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Peptide Fragments / administration & dosage
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Peptide Fragments / therapeutic use*
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Rats
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Rats, Wistar
Substances
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Myelin Proteins
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NEP1-40 protein, human
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Neuroprotective Agents
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Nogo Proteins
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Peptide Fragments
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RTN4 protein, human
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Rtn4 protein, rat
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1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
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fasudil