PMID- 12821376
OWN - NLM
STAT- MEDLINE
DCOM- 20030806
LR  - 20190722
IS  - 0014-4886 (Print)
IS  - 0014-4886 (Linking)
VI  - 182
IP  - 1
DP  - 2003 Jul
TI  - Ex vivo MR determined apparent diffusion coefficients correlate with motor 
      recovery mediated by intraspinal transplants of fibroblasts genetically modified 
      to express BDNF.
PG  - 49-63
AB  - The purpose of this study was to determine whether apparent diffusion 
      coefficients (ADCs) in ex vivo spinal cord white matter, calculated from 
      diffusion weighted MR (DWI) images, correlate with axonal growth and behavioral 
      recovery following subtotal hemisection and transplantation of fibroblasts 
      genetically modified to express brain derived neurotrophic factor (BDNF). These 
      genetically modified fibroblasts have been shown to promote axonal growth, 
      diminish retrograde degenerative changes in axotomized Red nucleus neurons, and 
      are associated with behavioral recovery. Since changes in ADC appear to reflect 
      damage to axons and myelin sheaths, which conventional MR techniques do not 
      identify, partial repair mediated by BDNF-secreting fibroblasts should be 
      detected with ADC measures. Accordingly, we transplanted unmodified fibroblasts 
      (Fb-UM) or fibroblasts modified to secrete BDNF (Fb-BDNF) into cervical subtotal 
      hemisection cavities in adult rats. Rats with Fb-BDNF transplants showed 
      significantly greater behavioral recovery over 12 weeks, as measured by tests of 
      forelimb exploration and open field locomotor activity. Lesion sizes and 
      transplant survival did not differ between the two groups, but immunocytochemical 
      examination showed substantial growth of axons into the Fb-BDNF grafts and little 
      growth into the Fb-UM grafts. Fixed spinal cords were imaged in a 9.4-T magnet. 
      ADCs perpendicular (tADC) and parallel (lADC) to the long axis of the cord were 
      measured in the dorsal lateral white matter, rostral and caudal to the 
      transplant. tADC values and anisotropy index (AI = tADC/lADC) were elevated in 
      both transplant types, indicating white matter damage, but were closer to normal 
      in rats with Fb-BDNF, consistent with known neuroprotection and axonal growth 
      elicited by BDNF. Closer to normal tADC and AI values correlated with improved 
      behavioral recovery. These findings suggest that high-resolution imaging with 
      measurement of tADC and lADC can provide a measure of functionally significant 
      repair that may otherwise go undetected with conventional MR techniques.
FAU - Schwartz, Eric D
AU  - Schwartz ED
AD  - Department of Radiology, Hospital of the University of Pennsylvania, 3400 Spruce 
      Street, 1 Silverstein, Philadelphia, PA 19104, USA. schwartz@rad.upenn.edu
FAU - Shumsky, Jed S
AU  - Shumsky JS
FAU - Wehrli, Suzanne
AU  - Wehrli S
FAU - Tessler, Alan
AU  - Tessler A
FAU - Murray, Marion
AU  - Murray M
FAU - Hackney, David B
AU  - Hackney DB
LA  - eng
GR  - NS02230/NS/NINDS NIH HHS/United States
GR  - NS24707/NS/NINDS NIH HHS/United States
GR  - NS25921/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
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)
SB  - IM
MH  - Animals
MH  - Anisotropy
MH  - Axons/physiology
MH  - Behavior, Animal
MH  - Brain-Derived Neurotrophic Factor/*biosynthesis/genetics/metabolism
MH  - Cell Division
MH  - Diffusion
MH  - Diffusion Magnetic Resonance Imaging
MH  - Disease Models, Animal
MH  - Female
MH  - Fibroblasts/metabolism/*transplantation
MH  - Graft Survival
MH  - Immunohistochemistry
MH  - Motor Activity
MH  - Neck
MH  - Predictive Value of Tests
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Recovery of Function
MH  - Spinal Cord/pathology/physiopathology
MH  - Spinal Cord Injuries/pathology/physiopathology/*therapy
EDAT- 2003/06/25 05:00
MHDA- 2003/08/07 05:00
CRDT- 2003/06/25 05:00
PHST- 2003/06/25 05:00 [pubmed]
PHST- 2003/08/07 05:00 [medline]
PHST- 2003/06/25 05:00 [entrez]
AID - S0014488603000360 [pii]
AID - 10.1016/s0014-4886(03)00036-0 [doi]
PST - ppublish
SO  - Exp Neurol. 2003 Jul;182(1):49-63. doi: 10.1016/s0014-4886(03)00036-0.