Abstract TP266: Platelet-Derived Glutamate Contributes to Neuronal Injury after Experimental Subarachnoid Hemorrhage
Bibliographic record
Abstract
Background: Glutamate toxicity (excitotoxicity) is well-studied in the pathogenesis of brain damage after cerebral ischemia and traumatic brain injury. Patients with subarachnoid hemorrhage (SAH) also have increased intracerebral glutamate as detected by microdialysis. While neurons and glia are potential sources of glutamate, platelets also release glutamate as part of their recruitment and might mediate neuronal damage. Studies have shown that intraluminal platelets escape into brain parenchyma after SAH. Therefore, we studied the hypothesis that formation of platelet microthrombi after SAH, and their subsequent extravasation releases glutamate that mediates excitotoxic brain injury and neuron dysfunction after SAH. Methods: We used two models, primary neuronal cultures exposed to activated platelets, and a model of SAH created by injection of 300 μl of fresh, unheparinized arterial blood into the prechiasmatic cistern of Sprague-Dawley rats (300-350 g). Glutamate was measured using amperometric microelectrode arrays. Propidium iodide was used to evaluate neuronal viability in neuronal cultures, and surface glutamate receptor immunohistochemical staining was used to evaluate the phenotype of platelet-exposed cultured neurons and brain after SAH. Microthrombi were stained with anti-fibrinogen antibodies. Results: We first demonstrated that thrombin-activated platelet-rich plasma releases glutamate in concentrations that exceed 300 μmol/l. When applied to neuronal cultures, this activated plasma was neurotoxic, and neurotoxicity was attenuated by glutamate receptor antagonism. Exposure of cultured neurons to thrombin-activated platelets induced a marked downregulation of the surface glutamate receptor GluR2, a marker of excitotoxicity and a possible mechanism of neuron dysfunction. Microthrombi were detected in rat cerebral cortex 7 days after SAH and linear regression demonstrated a strong correlation between proximity to microthrombi and reduction of surface glutamate GluR2 receptors. Conclusions: These correlative data support the novel hypothesis that platelet-mediated microthrombosis contributes to neuronal glutamate receptor dysfunction and might therefore influence clinical outcome following SAH.
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 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 | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".