Considerations in the selection of behavioural tests to gauge recovery after intracerebral hemorrhagic stroke in rats
Bibliographic record
Abstract
Cerebral ischemia and hemorrhage (stroke) are leading causes of death and disability. The goal of experimental cytoprotectants (neuroprotection) for stroke is to reduce cell death and thereby improve functional outcome. Rodents (rat, gerbil, mouse) are most commonly used to model ischemic and hemorrhagic insults. Despite the fact that behavioral recovery is the clinical endpoint of greater concern, many cytoprotection studies rely solely upon histopathological endpoints (e.g., infarct volume) to gauge treatment efficacy (DeBow et al., 2003; Can. J. Neurol. Sci). Furthermore, those studies that assess recovery often use only a neurological deficit score (NDS; e.g., paw placement, spontaneous rotation) and do not use more demanding / informative tests (e.g., skilled reaching). Successful translation of putative cytoprotectants from rodent models to human will depend upon how well treatments are initially assessed. Many functional tests are available in the rat and have been used in focal ischemia studies. Presently, we used a battery of functional tests, which are sensitive to sensory and motor system dysfunction, to gauge outcome after an intracerebral hemorrhagic stroke (ICH) largely targeting the striatum. Sixty adult male Sprague Dawley rats (N = 15 per group) were stereotaxically infused with 1 L of sterile saline containing 0 (SHAM), 0.06 (MILD lesion), 0.12 (MODERATE lesion), or 0.18 U (SEVERE lesion) of bacterial collagenase. Testing began one day following ICH and was repeated over 30 days. Tests included the horizontal ladder and beam walking tests, swimming, limb-use asymmetry (cylinder) test, a NDS, an adhesive tape removal test of sensory neglect, and the staircase and single pellet tests of skilled reaching. At present, the NDS, staircase, neglect and single-pellet tests have been analyzed. Overall, these tests revealed significant impairments (vs. SHAM) that improved over time (e.g., deficits on the NDS were greatest on days 1 and 2). However, despite significant differences in lesion size, we were often unable to statistically distinguish between MILD and MODERATE or MODERATE and SEVERE groups (e.g., neglect test). As for skilled reaching, the staircase test revealed significant contralateral forelimb impairments in the three ICH groups and was often able to distinguish among ICH groups. The SEVERE group also had significant ipsilateral impairments. Skilled reaching impairments were also found with the single-pellet test in the ICH groups. However, it was not possible to compare success among ICH groups because many rats in the MODERATE and SEVERE groups completely switched limb preference. Indeed, a detailed analysis of the entire reaching sequence with the contralateral limb was only possible in the SHAM and MILD groups. In conclusion, multiple behavioral tests are needed to comprehensively evaluate functional recovery after ICH. However, some tests (e.g., neglect test) are either not recommended for this model owing to the time required to test animals, variability, and the insensitivity to lesion size, or are of limited use (e.g., for small lesions). Finally, our results show that modest neuroprotection (e.g., reducing lesion size from SEVERE to MODERATE) may not consistently improve functional recovery, thereby necessitating the use of several tests.
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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 | 0.010 | 0.005 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.003 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| 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".