Abstract TP407: Combination of Minocycline and Neural Stem Cells Ameliorates Neurological Deficit in Aged Stroke Mice With Delayed Tpa Treatment
Bibliographic record
Abstract
The great promise of using stem cells to treat stroke has been inhibited by challenges to stem cell survival in the toxic environment of post-stroke tissue. Reperfusion (removal of clot) can be achieved mechanically (thrombectomy, <6-8hrs or by tissue plasminogen activator (tPA, <4.5 hrs), but ischemia/reperfusion injury limits the treatment time window. Furthermore, deleterious non-thrombolytic off-target effects of delayed tPA infusion (e.g., >4.5hrs) have been shown within brain parenchyma, increasing vascular injury and death of neurons. Previously, we reported that human neural stem cell (hNSC) transplantation 24hrs after stroke shows multiple beneficial short-term effects within 48hrs post-stroke, reducing inflammation, blood-brain barrier (BBB) damage, and infarct size. Since delayed tPA administration exacerbates BBB damage and increases hemorrhage, we reasoned that ameliorating inflammation and BBB damage by pretreating with neuroprotectants (i.e., minocycline) prior to tPA might synergize to expand the time window for tPA and provide a better environment for NSC survival, thus increasing NSC efficacy. We utilized the middle cerebral artery occlusion stroke mouse model to induce focal cerebral ischemia followed by reperfusion (MCAO/R). 6hrs post-MCAO, we administered tPA intravenously. Minocycline was administered intraperitoneally at various time points prior to tPA injection. One day post-stroke, we injected hNSCs intracranially. Previously, we reported that minocycline pretreatment prior to tPA and hNSC transplantation reduced the mortality of delayed tPA-treated aged mice within 48hrs post-stroke. In this study, we investigated the effect of hNSCs treated with minocycline-plus-delayed tPA treatment on long-term benefits on neurological function. We performed a behavioral test of motor function beginning 24hrs after hNSC transplantation. Rotarod test was carried out 3 days(d) consecutively pre-stroke (as training) and from 2d to 28d post-stroke. Here, we report that by combining minocycline prior to tPA significantly ameliorates neurological deficit in aged mice. Furthermore, transplanting hNSCs ameliorated the pathophysiology caused by delayed tPA.
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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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".