Extensive recovery of respiratory motor function at chronic and super-chronic time points following cervical SCI

The best abstracts come from the annual Society For Neuroscience Meeting and I like posting a few of my favorites for readers here at the blog.

Authors: *P. M. WARREN1, P. M. MACFARLANE2, J. SILVER3, W. J. ALILAIN1;
1Dept. of Neuroscience., Metro Health Med. Centre, Case Western Reserve Univ. Sch. of Med., Cleveland, OH; 2Dept. of Pediatrics, 3Dept. of Neuroscience ., Case Western Reserve Univ., Cleveland, OH

Treatments to restore respiratory function following chronic cervical spinal cord injury (SCI) have not been extensively studied. We provide evidence that a pharmacological agent and rehabilitative training may provide the key for recovery of diaphragm activity following chronic trauma. The ablation of respiratory function is caused by disruption of motoneuron pathways, formation of the chondroitin sulphate proteoglycan (CSPG) rich astroglial scar, and a reduction in interneuron, motoneuron and synaptic density. Following acute cervical SCI, CSPG breakdown by application of chrondroitinase ABC (ChABC) can restore functional diaphragm activity while intermittent hypoxia (IH) training increases respiratory drive and synaptic strength. We now provide evidence for the recovery of robust functional respiratory motor activity at both chronic (3 month) and super-chronic (1.5 year) time points following LC2H through a combination of IH training and ChABC. We used diaphragmatic electromyography (diaEMG) and phrenic nerve recordings to demonstrate that a single application of ChABC (0.005U) can recover extensive respiratory motor function following chronic and super-chronic SCI. Control treated animals showed no endogenous recovery of diaphragm function. While having limited effect upon diaEMG patterns, IH training alone was shown to enhance maximal phrenic nerve activity. However, the combined treatment of IH and ChABC was shown to substantially enhance diaEMG and maximal phrenic nerve activity beyond that demonstrated by either group alone. Interestingly, in a subpopulation of animals the muscle activity in this combination group can become unstructured, degrading patterned activity on the lesioned side. This tonic/chaotic activity is governed by a serotonergic (5-HT) mechanism and suggests considerable remodeling of spinal cord circuitry below the level of the lesion at chronic stages. Indeed, ChABC and IH treated animals which recover normal breathing patterns following treatment can be made chaotic by giving exogenous 5-HT, while those that are already chaotic can be normalized by blocking certain 5-HT receptors. These data demonstrate the significant restoration of diaphragm function and nerve activity at chronic and super-chronic time points following cervical SCI due to matrix modification, induction of plasticity and facilitation of drive. Yet, the potential emergence of chaos is indicative of the complications inherent in repairing the chronically injured spinal cord and suggest the need for tight mechanistic and environmental control.

Medical Press Article Link:  Laboratory breakthrough offers promise for spinal cord injury patients to breathe on their own again

Case Western Reserve researchers have developed a procedure that restores function to muscles involved in the control of breathing – even when they have been paralyzed for more than a year. The breakthrough offers hope that one day patients with severe spinal cord injuries will be able to breathe again without the assistance of a ventilator…

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