PirB restricts neuronal regeneration in developing rat brain following hypoxia-ischemia

Mol Med Rep. 2012 Aug;6(2):339-44. doi: 10.3892/mmr.2012.907. Epub 2012 May 8.

Abstract

The inhibitors of axonal regeneration in the myelin sheath are considered to be major contributors to the lack of regeneration in the central nervous system (CNS) following hypoxic-ischemic (HI) brain damage. As well as the Nogo receptor (NgR), the paired-immunoglobulin-like receptor B (PirB) is a functional receptor for the myelin inhibitors of axonal regeneration. The inhibition of PirB and NgR activities may block most of the inhibitory effects of myelin inhibitors on nerve regeneration. We observed the PirB protein and mRNA expression in HI-damaged rat cortical neurons using immunohistochemistry and reverse transcription-polymerase chain reaction assays. In addition, we treated the HI-damaged rat cortical neurons using PirB antibodies to observe the regeneration of injured neurons. Moreover, the Rock II activity in HI-damaged rat cortical neurons treated with PirB antibodies was observed using western blot analysis. The mRNA and protein levels of PirB increased in newborn rat cortical neurons following HI damage. Treatment with PirB antibodies is able to improve axonal regeneration following HI damage compared with normal axonal growth. Rock II activity also increased in the HI-damaged rat brain. The inhibition of PirB is therefore a potential therapeutic method to promote the regeneration of HI-damaged axons and the inhibitory signal may be transduced through the Rho-ROCK signaling pathway.

Keywords: paired immunoglobulin-like receptor B; neuron regeneration; developing rat brain; hypoxia-ischemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Blotting, Western
  • Brain / cytology
  • Cells, Cultured
  • Enzyme Activation
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism
  • Hypoxia-Ischemia, Brain / metabolism*
  • Hypoxia-Ischemia, Brain / pathology
  • Immunohistochemistry
  • Myelin Proteins / genetics
  • Myelin Proteins / metabolism
  • Nerve Regeneration*
  • Neurons / metabolism*
  • Neurons / pathology
  • Nogo Receptor 1
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • rho-Associated Kinases / metabolism

Substances

  • GPI-Linked Proteins
  • Myelin Proteins
  • Nogo Receptor 1
  • Pirb protein, rat
  • RNA, Messenger
  • Receptors, Cell Surface
  • Receptors, Immunologic
  • Rtn4r protein, rat
  • rho-Associated Kinases