Impact of treatment duration and lesion size on effectiveness of chondroitinase treatment post-SCI

Abstract

The effects of 2weeks of intralesional chondroitinase abc (ch'abc) treatment on anatomical plasticity and behavioral recovery are examined in adult cats and compared to results achieved with 4weeks of treatment following tightly controlled lateral hemisection injuries. Analyses also were completed using 35 cats with a range of hemisection magnitudes to assess relationships between treatment duration, lesion size and functional recovery. Results indicate that both 2 and 4weeks of treatment significantly increased the number of rubrospinal tract (RuST) neurons with axons below the lesion, but neither affected the number of corticospinal tract neurons. Similarly, both treatment periods also accelerated recovery of select motor tasks, which carries considerable importance with respect to human health care and rehabilitation. Four weeks of treatment promoted recovery beyond that seen with 2weeks in its significant impact on accuracy of movement critical for placement of the ipsilateral hindlimb onto small support surfaces during the most challenging locomotor tasks. Analyses, which extended to a larger group of cats with a range of lesion magnitudes, indicate that 4weeks of ch'abc treatment promoted earlier recovery as well as significantly greater targeting accuracy even in cats with larger lesions. Together, these results support the potential for ch'abc to promote anatomical and behavioral recovery and suggest that intraspinal treatment with ch'abc continues to enhance motor recovery and performance beyond the subacute injury period and diminishes the impact of lesion size.

Enhancing Fluorogold-based neural tract tracing

“…In particular, attention was paid to the dorsolateral funiculi, which contains the rubrospinal and corticospinal tracts used for labelling criteria. These two tracts were chosen for assessment in this study as we are well experienced with their tracing (Jefferson et al, 2011;Mondello et al, 2015) and, their cell bodies are located far from the injection sites.…”

“…The overall goal of this procedure is to label any descending axon that crosses the 9 th or 10 th thoracic spinal segment (a common level for experimental spinal cord injury). Our previous studies describe post-surgical procedures in detail (Tester and Howland, 2008;Jefferson et al, 2011;Mondello et al, 2015).…”

“…Animals fell into one of five different categories. The first was our longstanding protocol, 13 day FG without Triton TM injected at 21 weeks following a T10 left spinal hemisection (N=12; details about this FG injection procedure have been published established; Jefferson et al, 2011;Mondello et al, 2015). The four additional groups were: 7 day FG without Triton TM (N=1), 7 day FG with Triton TM (N=2), 3 day FG without Triton TM (N=1), and 3 day FG with Triton TM (N=3).…”

“…The method for producing a low thoracic (T9 or 10) hemisection can be found in prior publications (Tester and Howland, 2008;Jefferson et al, 2011;Mondello et al, 2015).…”

“…It also has strong fluorescent properties that make it readily detectable without additional processing if present in a large enough quantity. Further, the availability of a specific antibody allows its signal to be amplified and detected using immunohistochemistry (IHC) for both light and electron microscopic approaches (for examples see: Chang et al, 1990;Van Bockstaele et al, 1994;Deller et al, 2000;Naumann et al, 2000;Akhavan et al, 2006;Ruggieri et al, 2011;Jefferson et al, 2011;Mondello et al, 2015).…”