Nandakumar Nagaraja,  MD, MS

Premotor Cortex Shows a Reduction in Inhibitory Markers and Mediates Recovery in a Mouse Model of Focal Stroke. Stroke. 2013; 44: 483-489


Some patients with stroke regain the lost function partially or completely. Cortical reorganization adjacent to the damaged cortex is thought to be one of the mechanisms that could result in reduction in impairment. Zeiler and colleagues performed a study in a mouse model of focal motor stroke to show that reorganization in the medial premotor area (medial agranular cortex, AGm) mediates recovery of motor function and is associated with decreased inhibitory interneuron markers.

Adult male C57bl/6 mice 70-120 days old were trained to reach for the pellets placed on a sticky tape on a movable steel bar positioned 0.5cm away from the cage. They were trained until they reached 30% grasping success rate. Then the distance between the cage and the pellets was increased to 1cm to increase the difficulty of the task. 9-11days after training, focal stroke in the motor cortex for the preferred forelimb was induced by photothrombosis of cortical microvessels using a fiber optic bundle of a cold light source. This resulted in decreased skilled motor reaching accuracy that recovered after 5-6 training days.

A second stroke induced in the AGm led to decline in the skilled motor reaching accuracy that was recovered after first stroke. Stroke in AGm alone without prior infarct in motor cortex had no effect on skilled motor reaching accuracy suggesting AGm is necessary for recovery of motor function.

Animals were sacrificed 6-7 days after stroke and examined for inhibitory cortical interneuron markers parvalbumin, calretinin and calbindin. These markers were reduced only in AGm in mice that were retrained after focal motor stroke suggesting that decrease in inhibitory neurons is associated with post stroke recovery.

Understanding the mechanisms and factors associated with recovery of function could translate into implementing effective treatment strategies to minimize disability. In this study the authors have established a mouse model with double lesion approach to understand the mechanisms of post stroke recovery. Further studies at the cellular and molecular level with this mouse model may shed light on mechanism of brain plasticity in post stroke recovery.