A Triple Combination Approach Involving Nerve Transplantation, Glial Scar Digestion and Passive Exercise Promotes Cardiovascular Recovery after Spinal Cord Injury
Bibliographic record
Abstract
Introduction 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, ), 42.2% reduction in diastolic BP elevation (42.5 vs. 24.5 mmHg, p<0.001, ), 57.6% reduction in mean arterial pressure elevation (54.2 vs. 22.9 mmHg, p<0.001, ) as well as abolishment of CRD‐induced bradycardia (−80.2 vs. +14.6 bpm, p=0.056, ). 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).
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".