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The effects of brain-derived neurotrophic factor and intraspinal marrow stromal cell transplantation in a rat model of experimental spinal cord injury

Ankeny, Daniel P.
http://rave.ohiolink.edu/etdc/view?acc_num=osu1040224622

Abstract Details

2003, PhD, Ohio State University, Physiology.
Because of insufficient self-repair, recovery from spinal cord injury (SCI) is limited. The neurotrophin brain-derived neurotrophic factor (BDNF) shows promise for SCI treatment, although significant barriers to delivery have been identified. Therefore, the effects of pegylated BDNF (peg-BDNF, a pharmacologically modified BDNF protein) on repair and recovery were examined after experimental rat SCI. Morphological analysis revealed significantly improved delivery of peg-BDNF compared to unmodified BDNF. However, peg-BDNF did not improve anatomical or functional responses observed with unmodified BDNF. Both interventions stimulated accelerated locomotor recovery and hindlimb airstepping (a spontaneous locomotor movement). Similarly, neither treatment induced tissue sparing or axon regeneration, although both provoked sprouting in cholinergic axons. Of the factors potentially limiting BDNF's effects, the paucity of tissue within the lesion is a fundamental problem that may limit repair, since studies suggest promising effects of intralesion tissue transplantation. Recently, marrow stromal cells (MSCs-stem cells found in adult bone marrow) have been considered for such transplantation. To examine the effects of MSC transplants and explore the idea that BDNF's actions are limited by the paucity of growth-supportive tissue, rats received SCI and intraspinal transplantation of cultured MSCs with or without peg-BDNF co-infusion. Stereological analysis revealed that MSCs were well-tolerated, partially filling the cavities normally observed after SCI. Furthermore, MSCs provoked tissue and myelin sparing and supported properly oriented axon regeneration, demonstrating protective and reparative actions. Additionally, MSCs stimulated spontaneous airstepping, suggesting locomotor activation. Although BDNF / MSC co-treatment did not improve functional recovery, axon regeneration was significantly enhanced, compared to MSC transplantation alone. The protective effects of MSCs, however, were negated by BDNF co-infusion, demonstrating that more progress is needed before this combinatorial intervention could be applied to patients. Thus, BDNF delivery alone is not sufficient to stimulate functional recovery or significant repair after SCI. However, when delivered in the presence of a regeneration-supportive matrix, BDNF effectively stimulates regeneration. Additionally, MSCs may be an attractive source of transplant tissue for SCI intervention, since the transplants are tissue protective, enhance regeneration, and stimulate locomotor activities. Thus, these studies should aid in developing future strategies aimed at improving SCI outcomes.
Bradford Stokes (Advisor)
186 p.
Biology, Neuroscience
spinal cord injury; BDNF; bone marrow stromal cell; neurotransplantation; axon; regeneration

Recommended Citations

Citations

  • Ankeny, D. P. (2003). The effects of brain-derived neurotrophic factor and intraspinal marrow stromal cell transplantation in a rat model of experimental spinal cord injury [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1040224622

    APA Style (7th edition)

  • Ankeny, Daniel. The effects of brain-derived neurotrophic factor and intraspinal marrow stromal cell transplantation in a rat model of experimental spinal cord injury. 2003. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1040224622.

    MLA Style (8th edition)

  • Ankeny, Daniel. "The effects of brain-derived neurotrophic factor and intraspinal marrow stromal cell transplantation in a rat model of experimental spinal cord injury." Doctoral dissertation, Ohio State University, 2003. http://rave.ohiolink.edu/etdc/view?acc_num=osu1040224622

    Chicago Manual of Style (17th edition)

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This open access ETD is published by The Ohio State University and OhioLINK.