Survival effects of BDNF and NT-3 on axotomized rubrospinal neurons depend on the temporal pattern of neurotrophin administration.
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.
Novikova
L N
LN
Department of Integrative Medical Biology, Section for Anatomy, Umeå University, S-901 87 Umeå, Sweden.
Novikov
L N
LN
Kellerth
J O
JO
D000344:Afferent Pathways / Q000187:drug effects / Q000473:pathology; D000818:Animals; D001284:Atrophy; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D002574:Cervical Vertebrae; D002946:Cisterna Magna; D004334:Drug Administration Schedule; D004357:Drug Synergism; D005260:Female; D006984:Hypertrophy; D015918:Infusion Pumps, Implantable; D007263:Infusions, Parenteral; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D020933:Neurotrophin 3 / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000096:biosynthesis / Q000235:genetics; D012012:Red Nucleus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012183:Retrograde Degeneration / Q000209:etiology / Q000517:prevention & control*; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013119:Spinal Cord Injuries / Q000150:complications / Q000188:drug therapy / Q000473:pathology*; D020824:Spinocerebellar Tracts / Q000187:drug effects* / Q000473:pathology; D013346:Subarachnoid Space; D013997:Time Factors
D019208:Brain-Derived Neurotrophic Factor; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D020933:Neurotrophin 3; D020813:Receptor, trkB