PMID- 11421586
OWN - NLM
STAT- MEDLINE
DCOM- 20010802
LR  - 20181130
IS  - 0014-4886 (Print)
IS  - 0014-4886 (Linking)
VI  - 170
IP  - 1
DP  - 2001 Jul
TI  - Pegylated brain-derived neurotrophic factor shows improved distribution into the 
      spinal cord and stimulates locomotor activity and morphological changes after 
      injury.
PG  - 85-100
AB  - 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.
CI  - Copyright 2001 Academic Press.
FAU - Ankeny, D P
AU  - Ankeny DP
AD  - Department of Physiology and Cell Biology, The Ohio State University, Columbus, 
      OH 43210, USA.
FAU - McTigue, D M
AU  - McTigue DM
FAU - Guan, Z
AU  - Guan Z
FAU - Yan, Q
AU  - Yan Q
FAU - Kinstler, O
AU  - Kinstler O
FAU - Stokes, B T
AU  - Stokes BT
FAU - Jakeman, L B
AU  - Jakeman LB
LA  - eng
GR  - NS37321/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Exp Neurol
JT  - Experimental neurology
JID - 0370712
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - EC 2.3.1.6 (Choline O-Acetyltransferase)
SB  - IM
MH  - Animals
MH  - Axons/drug effects/pathology
MH  - Behavior, Animal/drug effects
MH  - Brain-Derived Neurotrophic Factor/administration & dosage/analogs & 
      derivatives/*pharmacokinetics
MH  - Choline O-Acetyltransferase/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Hindlimb
MH  - Immunohistochemistry
MH  - Injections, Spinal
MH  - Motor Activity/*drug effects
MH  - *Polyethylene Glycols/chemistry
MH  - Rats
MH  - Recovery of Function/drug effects
MH  - Spinal Cord/*drug effects/metabolism/pathology
MH  - Spinal Cord Injuries/*drug therapy/metabolism/pathology
MH  - Wounds, Nonpenetrating
EDAT- 2001/06/26 10:00
MHDA- 2001/08/03 10:01
CRDT- 2001/06/26 10:00
PHST- 2001/06/26 10:00 [pubmed]
PHST- 2001/08/03 10:01 [medline]
PHST- 2001/06/26 10:00 [entrez]
AID - S0014-4886(01)97699-X [pii]
AID - 10.1006/exnr.2001.7699 [doi]
PST - ppublish
SO  - Exp Neurol. 2001 Jul;170(1):85-100. doi: 10.1006/exnr.2001.7699.