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A Triple Combination Approach Involving Nerve Transplantation, Glial Scar Digestion and Passive Exercise Promotes Cardiovascular Recovery after Spinal Cord Injury
Author(s) -
Sachdeva Rahul,
Gopaul Rayshad,
Jia Mengyao,
Monga Aaron,
Ramer Matt,
Krassioukov Andrei V.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1077.7
Subject(s) - medicine , spinal cord injury , calcitonin gene related peptide , dorsal root ganglion , lesion , spinal cord , nociception , anesthesia , endocrinology , pathology , neuropeptide , receptor , psychiatry
Cardiovascular (CV) dysfunction is the leading cause of morbidity and mortality after spinal cord injury (SCI). SCI causes CV dysfunction primarily by (a) the direct loss of critical medullary control of sympathetic pre‐ganglionic neurons and, (b) the aberrant sprouting of nociceptive afferent fibers within the spinal cord. To promote significant CV recovery after SCI, we developed a triple combination approach to simultaneously promote axonal regeneration to regain the supraspinal vasomotor control as well as to reduce aberrant sprouting of nociceptive afferent fibers in an experimental model of SCI. Methods Adult male Wistar rats (n=40) received a complete spinal transection (Tx) at 3rd thoracic segment. The treatment group received peripheral nerve grafts (PNGs) spanning the lesion, intrathecal chondroitinase enzyme (ChABC) and cycling exercise beginning on day 5 (1 hr/day, 5 days/week). Appropriate control groups received Tx only or Tx and a single intervention. At 8 weeks post injury, CV function [i.e. resting blood pressure (BP), heart rate and pressor response to colorectal distension (CRD)] was assessed using radiotelemetry. Functional regeneration across PNGs was determined using stimulus driven units below the lesion upon electrical stimulation at cervical level. Neural tract tracing and immunohistochemistry was performed to quantify the number of regenerating neurons as well as the sprouting of nociceptive (calcitonin gene related peptide positive) afferent fibers. Results The preliminary findings (n= 5/group) show that the combination approach (Tx+PNG+ChABC+Ex) leads to significant CV recovery compared to the untreated group (Tx alone). Specifically, in response to CRD, the treatment group shows 53.8% reduction in systolic BP elevation (77.8 vs. 37.7 mmHg, p<0.0001, Fig. A), 42.2% reduction in diastolic BP elevation (42.5 vs. 24.5 mmHg, p<0.001, Fig. B), 57.6% reduction in mean arterial pressure elevation (54.2 vs. 22.9 mmHg, p<0.001, Fig. C) as well as abolishment of CRD‐induced bradycardia (−80.2 vs. +14.6 bpm, p=0.056, Fig. D). Synaptically driven activity of spinal cord neurons at T4 level upon electrical stimulation above the injury confirmed the functional re‐connection of regenerating axons. Histological studies are underway to further investigate the regeneration/plasticity related mechanisms underlying recovery. Conclusion Combined neuro‐regenerative and rehabilitative approach leads to significant recovery of CV function after SCI, which is likely mediated by vasomotor regeneration and afferent plasticity manipulation. Support or Funding Information Present study was supported by the Rick Hansen Foundation start up funding and the Heart and Stroke Foundation of Canada (AVK).