Warren J. Alilain1,2 and Jerry Silver1
1:Department of Neurosciences, Case Western Reserve University School of Medicine,
2:Department of Neurosciences, Rammelkamp Center for Education and Research/Metrohealth Medical Center Cleveland, OH USA
SFN Abstract – New Orleans, LA 2012
Most spinal cord injuries (SCI) are at the cervical level. This can result in disruption of bulbospinal inputs to phrenic motor neurons which innervate the diaphragm. This oftentimes results in the inability to breathe and the need for mechanical ventilation, severely diminishing the quality of life of those afflicted with the injury. In our laboratory we utilize a lateral C2 hemisection model of SCI which results in paralysis of the ipsilateral hemidiaphragm to study the anatomical and physiological changes which take place after cervical injury and strategies to restore function. A majority of studies have investigated treatments at acute stages, within 1 week of injury, to restore respiratory motor function. Since a majority of the human SC injured population is at chronic stages, it is necessary to investigate if these same strategies are still effective long after the initial injury. One cannot assume that treatments that are effective at acute stages will be equally as effective later on since a variety of untoward changes may occur over time. One strategy that has well characterized positive regenerative/sprouting effects at acute stages is treatment with chondroitinase ABC (ChABC). ChABC breaks down inhibitory chondroitin sulfate proteoglycans (CSPGs) in the lesion scar and the perineuronal net (PNN) – which are upregulated immediately following injury and potently inhibit plasticity and regeneration. In the current study we found that ChABC treatment alone at “super” chronic stages – 1 and 1.5 years post injury – can, indeed, restore hemidiaphragmatic function. Additionally, our data suggests that the restored function is greater than that which returns after acute treatment. Overall, this data suggests that at super-chronic injury states CSPGs and the PNN are still present and inhibitory to endogenous mechanisms to restore function. However, when enzymatically removed with ChABC alone, there is an enhanced response compared to acute treatment, further suggesting that precisely targeting CSPGs may be an important priority even in chronic SCI patients.