Correlates of Post-Stroke Brain Plasticity, Relationship to Pathophysiological Settings and Implications for Human Proof-of-Concept Studies

Abstract

The promotion of neurological recovery by enhancing neuroplasticity has recently obtained strong attention in the stroke field. Experimental studies support the hypothesis that stroke recovery can be improved by therapeutic interventions that augment neuronal sprouting. However plasticity responses of neurons are highly complex, involving the growth and differentiation of axons, dendrites, dendritic spines and synapses, which depend on the pathophysiological setting and are tightly controlled by extracellular and intracellular signals. Thorough mechanistic insights are needed into how neuronal plasticity is influenced by plasticity-promoting therapies in order not to risk the success of future clinical proof-of-concept studies.

Keywords: clinical translation; neuronal differentiation; neuronal plasticity; neuronal regeneration; restorative therapy.

Figure 1

Neuronal plasticity features of cortical neurons in response to stroke and neuronal growth stimulation. (A) Organization of the corticospinal tract previous to the stroke. Ipsilesional fibers are depicted in black and contralesional fibers in blue. (B) After ischemic stroke induced by middle cerebral artery occlusion, pyramidal tract axons in the ipsilesional hemisphere degenerate (dashed lines), whereas contralesional pyramidal tract axons and dendrites exhibit scarce sprouting. (C) After growth stimulation, short-distance cortical dendrites exhibit abundant sprouting both ipsilateral (black) and contralateral (green) to the stroke, whereas long-distance axon collaterals grow out across the midline (exemplified here at the level of the red and facial nuclei and spinal chord) in direction to denervated target neurons. Post-stroke, the augmentation of contralesional axon collateral sprouting is accompanied by the improvement of motor and coordination deficits.