Evaluation of long-term functional deficits following transient cerebral ischemia in two mouse strains

Nowadays, no suitable animal model exists to assess long-term disabilities after cerebral ischemia. The aim of this study was to compare long-term behavioral and histological differences between two common mouse strains (129S2/SvPasCrl and C57BL6H) after 30 minutes of middle cerebral artery occlusion (MCAo). Sensorimotor assessments were conducted at one and at three weeks post-surgery using accelerated Rotarod and open-field locomotion. Long-term behavioral testing began four weeks after MCAo using operant conditioning in a progressive fixed-ratio (FR) schedule. Experiments ended with volumetric determination of the infarcted area using NeuN immunostaining. Although no effect of ischemia was detected in 129S2 mice using these tests, in C57 mice, results showed obvious short-term motor and locomotor deficits. Furthermore, subtle but persistent disturbances of endurance and executive functioning were recorded by the progressive schedule tests but not highlighted by sensorimotor tests. Ischemic lesion extended to the dorsolateral part of the striatum in both strains and recurrent cortical damages were also observed in C57 mice. All those results are in accordance with inherent morphological and behavioral features of each strain. Since the motor cortex is spared by 30 minutes MCAo, functional disabilities could be related to striatal damages. In conclusion, C57BL/6H mouse strain, by offering an acceptable survival rate and enough sensitivity to MCAo, seems to be a mouse strain suitable to evaluate long-term deficits and possible functional recovery after cerebral ischemia.