title: Dose-dependent Nerve Inflammatory Response to rhBMP-2 in a Rodent Spinal Nerve Model.
abstract: METHODS
  We developed a spinal nerve root wrapping rodent model to evaluate the relationship between recombinant human bone morphogenetic protein 2 (rhBMP-2) dosage and the degree of inflammation.
  
  
  OBJECTIVE
  To investigate the direct effects of recombinant human bone morphogenetic protein 2 (rhBMP-2) dosage and the degree of inflammation in rodent spinal nerve roots.
  
  
  BACKGROUND
  rhBMP-2 is commonly used in clinical practice to augment spinal fusion. However, complications such as postoperative leg pain, and a higher rate of postoperative neurologic deficits have been reported. These may be attributable to the exposure of adjacent nerve roots to high doses of rhBMP-2.
  
  
  METHODS
  Eighteen rats were randomized into three groups as follows: Group 1: absorbable collagen sponge (ACS) + 10 μg rhBMP-2, Group 2: ACS + 1 μg rhBMP-2, and Group 3 ACS with 20 μL saline. The ACS containing rhBMP-2 or saline were then wrapped around the L5 nerve root and secured loosely with nonabsorbable sutures. At 1-week postoperation, the rats were sacrificed, and the L5 nerve root and dorsal root ganglion harvested for reverse transcription polymerase chain reaction (RT-PCR), histology and immunohistochemical staining.
  
  
  RESULTS
  In our study, 10 μg rhBMP-2 induced a 10-fold increase in seroma compared with 1 μg group. Using RT-PCR, macrophage markers MIP3-α, and CD-68 were upregulated by 8- and 2-fold respectively in comparison with the saline group. Haematoxylin and eosin (H&E) images demonstrated disruption of nerve structures in the high dose 10 μg rhBMP-2, but not at 1 μg rhBMP-2 and with saline.
  
  
  CONCLUSIONS
  High doses of rhBMP-2 induced neuroinflammation in a dose dependent manner, resulting in higher seroma volume, macrophage marker gene expressions, and higher proportions of immunohistochemically stained TNF-alpha and more macrophage infiltration.
  
  
  METHODS
  2.
authors.affiliation: Department of Orthopaedic Surgery, National University Hospital, Singapore, Singapore.
authors.forename: Zi Qiang Glen
authors.initials: ZQG
authors.lastname: Liau
authors.affiliation: Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Raymond Wing Moon
authors.initials: RWM
authors.lastname: Lam
authors.affiliation: Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Tao
authors.initials: T
authors.lastname: Hu
authors.affiliation: Department of Orthopaedic Surgery, National University Hospital, Singapore, Singapore.|Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Hee-Kit
authors.initials: HK
authors.lastname: Wong
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D004195:Disease Models, Animal; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D008159:Lumbar Vertebrae / Q000187:drug effects* / Q000601:surgery; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D013123:Spinal Fusion / Q000379:methods; D013127:Spinal Nerves / Q000187:drug effects* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D055396:Bone Morphogenetic Protein 2; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; C499469:recombinant human bone morphogenetic protein-2