Ultrasound-guided intraparenchymal injection of slow release Chondroitinase ABC-37 in the chronic phase of spinal cord injury improves long-term recovery
Bibliographic record
Abstract
It is well-established that early treatment with chondroitinase ABC (ChABC) improves functional recovery in preclinical models of spinal cord injury (SCI). To increase the potential for clinical translation, research is now focused on optimizing treatment conditions and enhancing the enzymatic stability of ChABC formulations. The current study tested the in vivo efficacy of a novel formulation of ChABC, Src homology-3 (SH3)-ChABC-37, that has 37 mutations and is delivered by affinity release from a crosslinked methylcellulose (xMC) modified with SH3-binding peptides (bp). The study also tested a gap in knowledge, comparing the effects of the route of administration on the efficacy of SH3-ChABC-37/xMC-bp. Male Sprague Dawley rats were given a single subarachnoid injection or a novel ultrasound guided intraparenchymal injection of SH3-ChABC-37/xMC-bp or vehicle (xMC-bp only), 28 days after a moderate, lower thoracic contusion injury. Recovery of locomotor and sensory function was assessed for 27 days post SCI, and prior to SH3-ChABC-37/xMC-bp treatment, and then following treatment until 112 days post SCI. We found that the single intraparenchymal injection of SH3-ChABC-37/xMC-bp produced a significant 1.5-point increase in BBB scores after day 28. There was no effect of subarachnoid administered SH3-ChABC-37/xMC-bp. Importantly, irrespective of the administration route, SH3-ChABC-37/xMC-bp did not produce pain. While pain symptoms worsened after day 28 in rats treated with xMC-bp only, SH3-ChABC-37/xMC-bp blocked further development of pain symptoms. These data confirm the in vivo efficacy of SH3-ChABC-37/xMC-bp and indicate that intraparenchymal administration may further improve treatment efficacy, even when applied in the chronic phase of SCI.
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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 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 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".