State-of-the-Art Techniques to Causally Link Neural Plasticity to Functional Recovery in Experimental Stroke Research.

Anna-Sophia Wahl

doi:10.1155/2018/3846593

Abstract

Current experimental stroke research faces the same challenge as neuroscience: to transform correlative findings in causative ones. Research of recent years has shown the tremendous potential of the central nervous system to react to noxious stimuli such as a stroke: Increased plastic changes leading to reorganization in form of neuronal rewiring, neurogenesis, and synaptogenesis, accompanied by transcriptional and translational turnover in the affected cells, have been described both clinically and in experimental stroke research. However, only minor attempts have been made to connect distinct plastic remodeling processes as causative features for specific behavioral phenotypes. Here, we review current state-of the art techniques for the examination of cortical reorganization and for the manipulation of neuronal circuits as well as techniques which combine anatomical changes with molecular profiling. We provide the principles of the techniques together with studies in experimental stroke research which have already applied the described methodology. The tools discussed are useful to close the loop from our understanding of stroke pathology to the behavioral outcome and may allow discovering new targets for therapeutic approaches. The here presented methods open up new possibilities to assess the efficiency of rehabilitative strategies by understanding their external influence for intrinsic repair mechanisms on a neurobiological basis.

Highlights

Huge efforts have been made in recent years, both by clinicians and basic researchers, we have still gained limited insights into a neurological disease such as stroke preventing us from developing specific cures and resulting in poor statistical numbers: Of 15 million people suffering from an ischemic brain attack every year, a third dies, a third remains permanently disabled, and a third recovers as the stroke itself has not been too devastating
Research of recent years has shown the tremendous potential of the central nervous system to react to noxious stimuli such as a stroke: Increased plastic changes leading to reorganization in form of neuronal rewiring, neurogenesis, and synaptogenesis, accompanied by transcriptional and translational turnover in the affected cells, have been described both clinically and in experimental stroke research
We provide the principles of the techniques together with studies in experimental stroke research which have already applied the described methodology

Summary

Introduction

Huge efforts have been made in recent years, both by clinicians and basic researchers, we have still gained limited insights into a neurological disease such as stroke preventing us from developing specific cures and resulting in poor statistical numbers: Of 15 million people suffering from an ischemic brain attack every year, a third dies, a third remains permanently disabled, and a third recovers as the stroke itself has not been too devastating. According to the neurologists’ saying “time is brain,” even mobile units have been established to bring the hospital to the patient [1] These efforts aim at increasing the number of patients being eligible for the only currently approved acute treatment—thrombolysis or thrombectomy—within a very early time window of 4.5 h after stroke [2, 3]. Only minor attempts have been made to transform pure correlative data into causative ones, which would enable a causal connection of plastic remodeling processes in the brain with distinct behavioral outcomes. Would this allow us to form a new understanding of the functional brain status after stroke, and it opens up possibilities to develop and test the efficiency of new Neural Plasticity therapeutic approaches. As the philosopher of science Karl Popper might have argued: Before we can provide answers, we need the power to ask new questions

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Conclusion