Modulation of the BK Channel During Acute Spinal Cord Injury is Neuroprotective
Bibliographic record
Abstract
Spinal cord injury results in significant neuronal and glial cell death resulting in impaired neurological and motor function. While there are often surviving axonal tracts, these are frequently dysmyelinated or demyelinated. Key to this pathology is uncontrolled Ca 2+ entry, resulting in excitotoxicity and cell death. We propose that by activating mechanisms attenuating global depolarization and limiting Ca 2+ entry, we can reduce neuronal death and significantly improve neurological and motor function. To this effect, we previously demonstrated that the large‐conductance, voltage and Ca 2+ ‐activated K + (BK or Maxi K + ) channel is altered after SCI, and may play a part in the neuropathology of SCI. In this study, we set out to explore whether the use of a BK channel activator, Isopimaric acid (ISO), is neuroprotective post spinal cord injury. Wister rats received a 25‐g clip compression injury at the T7 levels for 1 min. One hour post‐surgery, they were administered ISO (120 μM), Ibeurotoxin (IbTx; 100nM), or a vehicle control via mini‐osmotic pump. Complete gait analysis was performed using two‐dimensional motion capture by filming rats on a weekly basis for 8 weeks. Compound Action Potentials (CAP) and high frequency conduction experiments were performed on spinal cords 8 weeks post surgery. Finally, the size of the injury site, loss of myelination, and cell death were assessed using immunohistochemistry (IHC). Complete gait analysis suggests that treatment with ISO improves motor function in our test model. ISO treated animals were able to recover gait function to a greater extent than IbTx and control animals. While the IbTx treated rats also demonstrated an improvement in complete gait function, their recovery was delayed and not of the same magnitude as ISO treated animals. This finding was further supported in our electrophysiology and IHC experiments. In our CAP experiments we find that there is a significant difference between all three groups. Additionally, we found preservation or re‐establishment of axonal tracts and myelination in our IHC experiments. In conclusion, activation of the BK channel during acute SCI may be a novel therapeutic target for acute spinal cord injury. Further studies are required to determine if modulation of the BK channel in chronic injury is beneficial for recovery, and to understand the mechanisms by which this ion channel may be working during spinal cord injury repair. Support or Funding Information Saskatchewan Health Research Foundation
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 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".