Considerations in the selection of behavioural tests to gauge recovery after intracerebral hemorrhagic stroke in rats

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.

Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.