Alterations in recovery from spinal cord injury in rats treated with recombinant human bone morphogenetic protein-2 for posterolateral arthrodesis

Anton E. Dmitriev, Suzanne Castner, Ronald A. Lehman, Geoffrey Ling, Aviva J. Symes

Research output: Contribution to journalArticle

Abstract

Background: Treatment of trauma-related spinal instability with use of recombinant human bonemorphogenetic protein-2 (rhBMP-2) may appear as a viable option, but little is known of the direct effects of rhBMP-2 on the injured spinal cord. In the current study, we investigated the acute and long-term effects of using rhBMP-2 in the posterolateral spine at the level of a spinal cord injury in rats. Methods: Fifty-two rats underwent a T10 dorsal hemisection and were assigned to one of two groups: the vehicle control group (twenty-four rats) or the rhBMP-2 group (twenty-four rats). Within each group, animals were further subdivided according to the followup period: one week and six weeks after the lesion. For the acute phase, an additional group of four rats received recombinant human albumin, to account for the cross-species inflammatory response. Postoperatively, locomotor function was assessed on a weekly basis with use of an open field scale and digital footprint analysis. After the animals were killed, they were perfused and the spinal cords analyzed for inflammatory markers, gliosis, and extracellular matrix proteins with use of immunohistochemistry. Results: At one week, there was a significant increase in reactive astrocyte, macrophage-microglia, and fibroblast immunoreactivity around the lesion in the rhBMP-2-treated rats relative to controls. Additionally, there was increased staining for chondroitin sulfate proteoglycans. Similar intergroup morphologic differences persisted at six weeks. Functionally, in the acute phase, rhBMP-2-treated animals demonstrated more open field and finemotor control deficits relative to the controls.By six weeks, both groups had equivalent functional scores, but those treated with rhBMP-2 retained significantly greater paw angle changes than the control animals. Conclusions: Our findings indicate that in a rat model, rhBMP-2 use in the vicinity of a penetrating spinal cord injury triggers detrimental changes in the morphology of the spinal cord lesion and alters functional recovery. Clinical Relevance: Our findings suggest that rhBMP-2 used in its current form may impede neurologic recovery in a subset of patientswith an open dural spinal cord injury, aswe observed detrimental effects on histological and behavioral testing in our rat model.

Original languageEnglish (US)
Pages (from-to)1488-1499
Number of pages12
JournalJournal of Bone and Joint Surgery - Series A
Volume93
Issue number16
DOIs
Publication statusPublished - Aug 17 2011
Externally publishedYes

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ASJC Scopus subject areas

  • Surgery
  • Orthopedics and Sports Medicine

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