The
neurotrophin brain-derived neurotrophic factor (
BDNF) shows promise for the treatment of central nervous system (CNS)
trauma and disease. Effective delivery methods are required, however, for
BDNF to be useful as a therapeutic agent. To this end, we examined the penetration of intrathecally infused N-terminal pegylated
BDNF (peg-
BDNF) compared to similar infusion of native
BDNF after
spinal cord injury (SCI). Pegylation dramatically improved delivery of
BDNF to the spinal cord and induced the expression of Fos in spinal cord neurons. To test whether enhanced delivery would improve the modest effects on behavioral recovery and axonal outgrowth observed with native
BDNF infusion, we assessed the efficacy of 2-week 25 microg/day peg-
BDNF treatment, beginning 12-24 h (early) or 15 days (delayed) after midthoracic spinal
contusion. Similar to native
BDNF, early treatment with peg-
BDNF accelerated the recovery of stepping in the open-field and acutely stimulated locomotor central pattern generator activity, as seen by the activation of hindlimb airstepping during either period of administration. The infusion of peg-
BDNF, regardless of the timing of delivery, was related to enhanced sprouting of putative cholinergic fibers, like that observed after high dose native
BDNF treatment. Despite improved delivery, however, neither axonal responses nor the extent of locomotor recovery were enhanced compared to native
BDNF treatment. This suggests that alternative strategies, such as
neurotrophin treatment in conjunction with
cell transplantation techniques, or treatment nearer the cell bodies of target neurons might be employed in an attempt to effect significant repair after SCI.