Brain-Derived Neurotrophic Factor Gene Transfer With Adeno-Associated Viral and Lentiviral Vectors Prevents Rubrospinal Neuronal Atrophy and Stimulates Regeneration-Associated Gene Expression After Acute Cervical Spinal Cord Injury
Bibliographic record
Abstract
STUDY DESIGN: Experimental animal study. OBJECTIVE: To determine if viral vectors carrying the gene for brain-derived neurotrophic factor (BDNF) could be used to promote an axonal regenerative response in rubrospinal neurons after an acute cervical spinal cord injury. SUMMARY OF BACKGROUND DATA: Following axotomy in the cervical spinal cord, rubrospinal neurons undergo severe atrophy and fail to up-regulate important genes for regeneration. This can be attenuated or reversed with the infusion of BDNF to the injured cell bodies. This infusion technique, however, causes substantial parenchymal damage around the red nucleus and is limited by occlusion of the infusion pumps. This study examined whether viral vectors could be used to deliver the BDNF gene in a less damaging fashion and whether this could promote a regenerative response in injured rubrospinal neurons. METHODS: Following a cervical spinal cord injury, the viral vectors were injected into the vicinity of the injured red nucleus. The extent of parenchymal damage around the red nucleus was assessed, as was the immunoreactivity to BDNF and cellular transfection patterns. Rubrospinal neuronal cross-sectional area was measured to determine if atrophy had been reversed, and in situ hybridization for GAP-43 and Talpha1 tubulin was performed to determine if there genes, which are important for axonal regeneration, were up-regulated. RESULTS: Parenchymal damage associated with viral injection was significantly less than with previous infusion techniques. BDNF immunoreactivity around the red nucleus indicated that the BDNF transgene was expressed. Both viral vectors reversed rubrospinal neuronal atrophy and promoted the expression of GAP-43 and Talpha1 tubulin. CONCLUSIONS: Viral-mediated transfer of the BDNF gene was successful at promoting a regenerative response in rubrospinal neurons following acute cervical spinal cord injury, with significantly less parenchymal damage than previously observed when infusing the BDNF protein.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".