Abstract
This study shows that both BDNF and NT-3 can prevent cell death in axotomized adult rat rubrospinal neurons (RSNs), but that the efficacy of neuroprotection depends on the temporal pattern of treatment. At 8 weeks after cervical spinal cord injury, 51% of the RSNs had died. Subarachnoidal BDNF infusion into the cisterna magna for 4 weeks resulted in neuronal hypertrophy and 71% survival. Continuous infusion for 8 weeks into the lumbar subarachnoidal space with either BDNF or NT-3 gave similar survival rates, while a combination of BDNF and NT-3 resulted in 96% survival, although the cells were atrophic. When administration of either BDNF or NT-3 was delayed and performed during postoperative weeks 5-8, the number of surviving neurons was increased compared to early treatment. Delayed treatment with a combination of BDNF and NT-3 resulted in complete survival and a reduction in neuronal atrophy. A decreased expression of TrkB receptors and microtubule-associated protein-2 in the RSNs after axotomy was counteracted by BDNF and NT-3. Microglial activity remained increased even when complete cell survival was achieved. Thus, the combination of neurotrophins as well as the temporal pattern of treatment need to be adequately defined to optimize survival of injured spinal tract neurons.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Afferent Pathways / drug effects
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Afferent Pathways / pathology
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Animals
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Atrophy
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Brain-Derived Neurotrophic Factor / administration & dosage
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Brain-Derived Neurotrophic Factor / pharmacology
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Brain-Derived Neurotrophic Factor / therapeutic use*
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Cell Survival / drug effects
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Cervical Vertebrae
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Cisterna Magna
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Drug Administration Schedule
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Drug Synergism
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Female
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Hypertrophy
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Infusion Pumps, Implantable
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Infusions, Parenteral
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Microglia / metabolism
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Microglia / pathology
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Microtubule-Associated Proteins / biosynthesis
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Microtubule-Associated Proteins / genetics
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Nerve Tissue Proteins / biosynthesis
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Nerve Tissue Proteins / genetics
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Neurons / drug effects*
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Neurons / metabolism
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Neurons / pathology
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Neuroprotective Agents / administration & dosage
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Neuroprotective Agents / pharmacology
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Neuroprotective Agents / therapeutic use*
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Neurotrophin 3 / administration & dosage
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Neurotrophin 3 / pharmacology
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Neurotrophin 3 / therapeutic use*
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Rats
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Rats, Sprague-Dawley
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Receptor, trkB / biosynthesis
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Receptor, trkB / genetics
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Red Nucleus / drug effects*
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Red Nucleus / metabolism
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Red Nucleus / pathology
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Retrograde Degeneration / etiology
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Retrograde Degeneration / prevention & control*
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Spinal Cord / drug effects*
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Spinal Cord / metabolism
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Spinal Cord / pathology
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Spinal Cord Injuries / complications
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Spinal Cord Injuries / drug therapy
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Spinal Cord Injuries / pathology*
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Spinocerebellar Tracts / drug effects*
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Spinocerebellar Tracts / pathology
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Subarachnoid Space
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Time Factors
Substances
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Brain-Derived Neurotrophic Factor
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Microtubule-Associated Proteins
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Nerve Tissue Proteins
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Neuroprotective Agents
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Neurotrophin 3
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Receptor, trkB