<i>In vivo</i> cerebral microdialysis validation of the acute central glutamate response in a translational rat model of concussion combining force and rotation
Bibliographic record
Abstract
Abstract Concussions/mild traumatic brain injury (mTBI) represent a major public health concern due to persistent behavioral and neurological effects. The mechanisms by which concussions lead to such effects are partly attributable to an hyperacute indiscriminate glutamate release. Cerebral microdialysis studies in rodents reported a peak of extracellular glutamate 10 minutes after injury. Microdialysis has the advantage of being one of the few techniques allowing the quantification of neurotransmitters in vivo and at different time points following injury. In addition to the clear advantages afforded by microdialysis, the Wayne State weight-drop model induces an impact on the skull of a subject unrestrained by the fall of a weight. The latter model allows rapid acceleration and deceleration of the head and torso, an essential feature in human craniocerebral trauma and a factor that is missing from many existing animal concussion models. In the present study, we applied the Wayne State procedure and microdialysis to document, in awake rats, the acute changes in extracellular hippocampal glutamate and GABA levels resulting from concussive trauma. We studied the dorsal CA1 hippocampal region as it contains a high density of glutamatergic terminal and receptors, thus making it vulnerable to excitotoxic insult. Using HPLC, dialysate levels of hippocampal glutamate and GABA were measured in adult male Sprague-Dawley rats in 10 min increments for 60 min prior to, during and for 90 min following concussive trauma induced by the Wayne State weight-drop procedure. Sham control animals were treated in the same manner but without receiving the concussive trauma procedure. Our results show that concussive trauma is followed, within 10 min, by a robust, transient 3-fold increase in hippocampal glutamate levels; such changes were not seen in controls. In contrast, GABA levels were unaffected by the concussive trauma procedure. The findings derived from the approach used here are generally consistent with those of previous other studies. They also provide a crucial in vivo validation of the Wayne State procedure as a model with promising translational potential for pre-clinical studies on early therapeutic responses to concussion.
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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 | 0.001 |
| 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 | 0.001 |
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".