Treatment of penetrating brain injury in a rat model using collagen scaffolds incorporating soluble Nogo receptor

J Tissue Eng Regen Med. 2015 Feb;9(2):137-50. doi: 10.1002/term.1621. Epub 2012 Oct 5.


Injuries and diseases of the central nervous system (CNS) have the potential to cause permanent loss of brain parenchyma, with severe neurological consequences. Cavitary defects in the brain may afford the possibility of treatment with biomaterials that fill the lesion site while delivering therapeutic agents. This study examined the treatment of penetrating brain injury (PBI) in a rat model with collagen biomaterials and a soluble Nogo receptor (sNgR) molecule. sNgR was aimed at neutralizing myelin proteins that hinder axon regeneration by inducing growth cone collapse. Scaffolds containing sNgR were implanted in the brains of adult rats 1 week after injury and analysed 4 weeks or 8 weeks later. Histological analysis revealed that the scaffolds filled the lesion sites, remained intact with open pores and were infiltrated with cells and extracellular matrix. Immunohistochemical staining demonstrated the composition of the cellular infiltrate to include macrophages, astrocytes and vascular endothelial cells. Isolated regions of the scaffold borders showed integration with surrounding viable brain tissue that included neurons and oligodendrocytes. While axon regeneration was not detected in the scaffolds, the cellular infiltration and vascularization of the lesion site demonstrated a modification of the injury environment with implications for regenerative strategies.

Keywords: Nogo receptor; brain tissue engineering; collagen scaffold; penetrating brain injury; rat brain; traumatic brain injury.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Astrocytes / cytology
  • Axons / metabolism
  • Behavior, Animal
  • Biocompatible Materials / chemistry
  • Brain / pathology
  • Collagen / chemistry*
  • Endothelial Cells / cytology
  • GPI-Linked Proteins / metabolism
  • Glial Fibrillary Acidic Protein / metabolism
  • Head Injuries, Penetrating / therapy*
  • Immunohistochemistry
  • Inflammation
  • Macrophages / cytology
  • Male
  • Myelin Proteins / metabolism*
  • Myelin Sheath / chemistry
  • Nogo Receptor 1
  • Oligodendroglia / cytology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Cell Surface / metabolism*
  • Regenerative Medicine / methods
  • Tissue Engineering / methods*
  • Tissue Scaffolds / chemistry


  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Biocompatible Materials
  • CD68 antigen, human
  • GPI-Linked Proteins
  • Glial Fibrillary Acidic Protein
  • Myelin Proteins
  • Nogo Receptor 1
  • Receptors, Cell Surface
  • Rtn4r protein, rat
  • Collagen