Removing the brakes on post-stroke plasticity drives recovery from the intact hemisphere and spinal cord

Abstract

The existence of bilaterally redundant corticospinal pathways suggests a potential means of recovery after unilateral injury such as stroke. However, in the adult brain, plasticity is kept in check by inhibitory factors that provide the stability necessary in neuronal networks to encode memories and retain learned actions. In the current issue of Brain , Nicolas Lindau and colleagues use antibodies that block Nogo-A functioning to unlock plasticity within the adult injured brain, leading to a structural and functional re-routing of corticospinal signals to exploit circuit redundancy (Lindau et al. , 2014). After a large motor cortex stroke, there is evidence that the intact hemisphere can control the impaired hand and thus facilitate behavioural recovery (Grefkes and Ward, 2014). However, hemiparesis remains a common deficit after stroke, indicating a need for therapies that augment spontaneous recovery. Lindau et al. (2014) show that, in rats, promoting axonal sprouting by blocking the growth-inhibitor protein Nogo-A facilitates the emergence of motor pathways that allow the intact hemisphere to drive motor output to the impaired forelimb. Although only 10% of corticospinal projections terminated in the ipsilateral spinal cord before injury, anti-Nogo-A therapy induced the generation of additional ipsilateral motor projections and produced substantial recovery of forelimb function. During the development and refinement of the nervous system there is extensive axonal sprouting. To curb ebullient outgrowth in the adult, various inhibitory molecules such as Nogo-A keep the …