Neutralizing Intraspinal Nerve Growth Factor with a trkA-IgG Fusion Protein Blocks the Development of Autonomic Dysreflexia in a Clip-Compression Model of Spinal Cord Injury
Bibliographic record
Abstract
Increased intraspinal nerve growth factor (NGF) after spinal cord injury (SCI) is detrimental to the autonomic nervous system. Autonomic dysreflexia is a debilitating condition characterized by episodic hypertension, intense headache, and sweating. Experimentally, it is associated with aberrant primary afferent sprouting in the dorsal horn that is nerve growth factor (NGF)-dependent. Therapeutic strategies that neutralize NGF may ameliorate initial apoptotic cellular responses to the injury and aberrant afferent plasticity that occurs weeks after the injury. Subsequently, the development of autonomic disorders may be suppressed. We constructed a protein including the extracellular portion of trkA fused to the Fc portion of human IgG and expressed it using a baculovirus system. Binding of our trkA-IgG fusion protein was specific for NGF with a K(d) = 4.26 x 10(-11) M and blocked NGF-dependent neuritogenesis in PC-12 cells. We hypothesized that binding of NGF in the injured cord by our trkA-IgG fusion protein would diminish autonomic dysreflexia. Severe, high thoracic SCI was induced with clip compression and the rats were treated with intrathecal infusions (4 microg/day) of trkA-IgG or control IgG. At 14 days post-SCI, the magnitude of autonomic dysreflexia was assessed. Colon distension increased mean arterial pressure (MAP) in control rats by 46 +/- 2 from 96 +/- 5 mmHg. In contrast, MAP of rats treated with trkA-IgG increased by only 30 +/- 2 mmHg. Likewise, the MAP response to cutaneous stimulation was also reduced in rats treated with trkA-IgG (20 +/- 1 vs. 29 +/- 2). In contrast, trkA-IgG treatment had no effect on heart rate responses during colon distension or cutaneous stimulation. These results indicate that treatment with trkA-IgG to block NGF suppresses the development of autonomic dysreflexia after a clinically relevant spinal cord injury.
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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 | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.002 |
| 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".