Neuroprotective effects of NEP1-40 and fasudil on Nogo-A expression in neonatal rats with hypoxic-ischemic brain damage

Genet Mol Res. 2011 Nov 29;10(4):2987-95. doi: 10.4238/2011.November.29.9.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / administration & dosage
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / analogs & derivatives*
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / therapeutic use
  • Animals
  • Animals, Newborn
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / pathology
  • Carotid Arteries / drug effects
  • Carotid Arteries / metabolism
  • Carotid Arteries / pathology
  • Female
  • Gene Expression / drug effects
  • Hypoxia-Ischemia, Brain / genetics
  • Hypoxia-Ischemia, Brain / metabolism
  • Hypoxia-Ischemia, Brain / pathology
  • Hypoxia-Ischemia, Brain / prevention & control*
  • Immunohistochemistry
  • In Situ Hybridization
  • Injections, Intraperitoneal
  • Ligation / methods
  • Male
  • Myelin Proteins / administration & dosage
  • Myelin Proteins / biosynthesis*
  • Myelin Proteins / genetics
  • Myelin Proteins / therapeutic use*
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / therapeutic use*
  • Nogo Proteins
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / therapeutic use*
  • Rats
  • Rats, Wistar

Substances

  • Myelin Proteins
  • NEP1-40 protein, human
  • Neuroprotective Agents
  • Nogo Proteins
  • Peptide Fragments
  • RTN4 protein, human
  • Rtn4 protein, rat
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • fasudil