Rapid and robust recovery of breathing 1.5 years after cervical spinal cord injury

Dr. Pippa Warren

Methods to restore respiratory function following chronic cervical spinal cord injury (SCI) have not been extensively studied. This represents a major gap in our current understanding as the primary cause of morbidity and mortality following cervical SCI is respiratory motor dysfunction. The loss of this activity after SCI is caused by disruption to supraspinal control of motor pathways. We have previously shown that formation of the chondroitin sulphate proteoglycan (CSPG) rich perineuronal net is the major impediment to sprouting and reawakening of the residual cross-phrenic pathway that can lead to restoration of respiratory motor function. Indeed, our data demonstrate that robust and rapid recovery of respiratory motor function is possible up to 1.5 years following severe cervical spinal cord hemisection injury through a combination of enzymatic degradation of perineuronal net associated proteoglycans and rehabilitative conditioning. We now provide evidence that this recovery is essentially permanent, lasting up to six months following the cessation of treatment. Our combination treatment strategy mitigates these effects through CSPG breakdown by intraspinal injection of chrondroitinase ABC (ChABC) and intermittent hypoxia (IH) training to increase respiratory drive and synaptic strength. Following conclusion of our treatment strategy, immunohistochemistry has revealed that the extracellular matrix does not reform normally, perhaps suggestive of on-going plasticity. Further, we provide evidence that our combination treatment strategy allows for re-innervation of diaphragm neuromuscular junctions (NMJs) previously denervated due to paralysis induced atrophy. In addition, we provide data describing the ventilatory response of our animals throughout treatment detailing how our recovered animals respond to environmental challenge. Collectively, these data demonstrate the significant restoration of diaphragm function and nerve activity at chronic points following cervical SCI due to matrix modification, induction of plasticity and facilitation of drive. Indeed, our results indicate that essentially complete recovery of motor function in this model of spinal cord trauma may not be limited by time after injury.

Authors: *P. M. WARREN1,2, S. C. STEIGER3, T. E. DICK4, P. M. MACFARLANE5, W. J. ALILAIN6,2, J. SILVER2;
1Sch. of Biomed. Sci., Univ. of Leeds, Leeds, United Kingdom; 2Dept. of Neurosciences, 3Sch. of Biomed. Sci., Case Western Reserve Univ., Cleveland, OH; 4Dept. of Med., Case Western Res. Univ., Cleveland, OH; 5Pediatrics, RB&C, CWRU, Cleveland, OH; 6Anat. and Neurobio., Univ. of Kentucky, Lexington, KY
Disclosures: P.M. Warren: None. S.C. Steiger: None. T.E. Dick: None. P.M. MacFarlane: None. W.J. Alilain: None. J. Silver: None.

This entry was posted in Chronic Spinal Cord Injury Research, Neuroscience Abstracts, Spinal Research and tagged , . Bookmark the permalink.

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