Ln. Novikova et al., Survival effects of BDNF and NT-3 on axotomized rubrospinal neurons dependon the temporal pattern of neurotrophin administration, EUR J NEURO, 12(2), 2000, pp. 776-780
This study shows that both BDNF and NT-3 can prevent cell death in axotomiz
ed adult rat rubrospinal neurons (RSNs), but that the efficacy of neuroprot
ection depends on the temporal pattern of treatment. At 8 weeks after cervi
cal spinal cord injury, 51% of the RSNs had died. Subarachnoidal BDNF infus
ion into the cisterna magna for 4 weeks resulted in neuronal hypertrophy an
d 71% survival. Continuous infusion for 8 weeks into the lumbar subarachnoi
dal space with either BDNF or NT-3 gave similar survival rates, while a com
bination 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 perfo
rmed during postoperative weeks 5-8, the number of surviving neurons was in
creased compared to early treatment. Delayed treatment with a combination o
f BDNF and NT-3 resulted in complete survival and a reduction in neuronal a
trophy. A decreased expression of TrkB receptors and microtubule-associated
protein-2 in the RSNs after axotomy was counteracted by BDNF and NT-3. Mic
roglial activity remained increased even when complete cell survival was ac
hieved. Thus, the combination of neurotrophins as well as the temporal patt
ern of treatment need to be adequately defined to optimize survival of inju
red spinal tract neurons.