Apparent Diffusion Coefficients in Spinal Cord Transplants and Surrounding White Matter Correlate with Degree of Axonal Dieback After Injury in Rats

• Published in: American journal of neuroradiology : AJNR Vol. 26; no. 1; pp. 7 - 18
• Main Authors: Schwartz, Eric D, Chin, Chih-Liang, Shumsky, Jed S, Jawad, Abbas F, Brown, B. Kooper, Wehrli, Suzanne, Tessler, Alan, Murray, Marion, Hackney, David B
• Format: Journal Article
• Language: English
• Published: Oak Brook, IL Am Soc Neuroradiology 01-01-2005; American Society of Neuroradiology
• Subjects: Animals; Axons - pathology; Axons - physiology; Biological and medical sciences; Brain-Derived Neurotrophic Factor - pharmacology; Diffusion Magnetic Resonance Imaging; Electrodiagnosis. Electric activity recording; Female; Fibroblasts - transplantation; Fundamental and applied biological sciences. Psychology; Hindlimb - innervation; Image Processing, Computer-Assisted; Investigative techniques, diagnostic techniques (general aspects); Medical sciences; Nerve Regeneration - physiology; Nervous system; Neural Pathways - anatomy & histology; Perception; Prognosis; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Radiodiagnosis. Nmr imagery. Nmr spectrometry; Rats; Rats, Sprague-Dawley; Red Nucleus - pathology; Retrograde Degeneration - pathology; Retrograde Degeneration - physiopathology; Spinal Cord - pathology; Spinal Cord - physiopathology; Spinal Cord - transplantation; Spinal Cord Injuries - pathology; Spine; Statistics as Topic; Vision; Vertebrata; Spinal cord; Nervous system diseases; Mammalia; Radiodiagnosis; Rat; Animal; Rodentia; Central nervous system; Diffusion coefficient; White matter
• ISSN: 0195-6108; 1936-959X

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).
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.
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.
ADC values may be able to evaluate graft function after spinal cord injury by demonstrating the degree of axonal dieback and preservation.