Retrograde axonal tracing using manganese enhanced magnetic resonance imaging

Abstract

Manganese-enhanced magnetic resonance imaging (MEMRI) was used to investigate retrograde axonal tracing in the rat sciatic nerve model to assess its potential to examine peripheral nerve injury. The right sciatic nerve was exposed and crushed. After each recovery period, the distal part of the right sciatic nerve was injected with manganese (400 mM, 15 μl). After allowing 3 days for manganese transport the animals were subsequently scanned to visualize the sciatic nerve and its corresponding spinal cord and dorsal root ganglia with T1-weighted MRI. Thirty-four animals were randomly divided into 4 experimental groups according to their recovery period post-crush injury: 3 days (n=6), 2 weeks (n=6), 4 weeks (n=6) and 12 weeks (n=6); and two control groups: a non-crushed group (n=6) and a nerve cut group (n=4). In the no-injury group, the right sciatic nerve tract including its corresponding spinal cord and dorsal root ganglia showed significant T1 signal enhancement. In the animals with crush injury, the MR signal intensity was significantly reduced proximal to the injured site but gradually reappeared with increasing recovery period. The signal intensity of the sciatic tract was compared to the results of behavioral functional testing, retrograde axonal tracing with neural tracer fluorogold and histomorphometric analysis of the distal nerve. Significant correlations were observed between the MR signal intensity and the behavioral functional test (r=0.50, p<0.05), and the retrograde axonal tracing (r=0.88; p<0.05). Retrograde neuronal tract tracing with MEMRI can be used for the assessment of peripheral nerve damage and regeneration.