Apparent diffusion coefficients in spinal cord transplants and surrounding white matter correlate with degree of axonal dieback after injury in rats.
OBJECTIVE
Abnormal apparent diffusion coefficient (ADC) values in injured spinal cord white matter and fibroblast transplants have been shown to correspond with qualitative histologic findings of axonal loss or regeneration. We proposed that ADC values would correlate with quantitative axonal tracing in the transected rubrospinal tract (RST).


METHODS
Eleven rats received right-sided lateral funiculus lesions at C3-4 (disrupting the RST) and transplantation of fibroblasts that were unmodified or modified to secrete brain-derived neurotrophic factor (BDNF). Behavioral tests measured hindlimb function at 1, 2, 4, 6, 8, 10, and 12 weeks after injury. At 12 weeks after injury, the antegrade axon tracer biotinylated dextran amine was stereotactically injected into the red nucleus to label the injured RST axons. Animals were sacrificed 2 weeks later. Diffusion-weighted MR imaging of the excised, fixed spinal cord specimens was then performed at 9.4 T.


RESULTS
In white matter surrounding transplants, ADC values transverse to axons were elevated and ADC values longitudinal to axons were decreased. These ADC values were more abnormal closer to the transplant, and this correlated with decreases in numbers of labeled RST axons. ADC values in BDNF-expressing fibroblast transplants were significantly lower than those in unmodified fibroblast transplants, and these lower values correlated with decreased axonal dieback. Behaviorally, all animals showed partial recovery, but animals with BDNF-expressing fibroblast transplants had slightly improved hindlimb function compared to those with unmodified fibroblast transplants.


CONCLUSIONS
ADC values may be able to evaluate graft function after spinal cord injury by demonstrating the degree of axonal dieback and preservation.
Schwartz
Eric D
ED
Department of Radiology, University of Pennsylvania School of Medicine, Philadelphia 191047, USA.
Chin
Chih-Liang
CL
Shumsky
Jed S
JS
Jawad
Abbas F
AF
Brown
B Kooper
BK
Wehrli
Suzanne
S
Tessler
Alan
A
Murray
Marion
M
Hackney
David B
DB
D000818:Animals; D001369:Axons / Q000473:pathology* / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D005347:Fibroblasts / Q000637:transplantation; D006614:Hindlimb / Q000294:innervation; D007091:Image Processing, Computer-Assisted; D009416:Nerve Regeneration / Q000502:physiology*; D009434:Neural Pathways / Q000033:anatomy & histology; D011379:Prognosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012012:Red Nucleus / Q000473:pathology*; D012183:Retrograde Degeneration / Q000473:pathology* / Q000503:physiopathology; D013116:Spinal Cord / Q000473:pathology / Q000503:physiopathology / Q000637:transplantation*; D013119:Spinal Cord Injuries / Q000473:pathology*; D013223:Statistics as Topic
D019208:Brain-Derived Neurotrophic Factor