Protein Synthesis Inhibition in the Peri-Infarct Cortex Slows Motor Recovery in Rats.

Maximilian Schubring-Giese,Susan Leemburg,Andreas Rüdiger Luft,Jonas Aurel Hosp

doi:10.1371/journal.pone.0157859

Maximilian Schubring-Giese, Susan Leemburg + Show 2 more

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https://doi.org/10.1371/journal.pone.0157859

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Abstract

Neuroplasticity and reorganization of brain motor networks are thought to enable recovery of motor function after ischemic stroke. Especially in the cortex surrounding the ischemic scar (i.e., peri-infarct cortex), evidence for lasting reorganization has been found at the level of neurons and networks. This reorganization depends on expression of specific genes and subsequent protein synthesis. To test the functional relevance of the peri-infarct cortex for recovery we assessed the effect of protein synthesis inhibition within this region after experimental stroke. Long-Evans rats were trained to perform a skilled-reaching task (SRT) until they reached plateau performance. A photothrombotic stroke was induced in the forelimb representation of the primary motor cortex (M1) contralateral to the trained paw. The SRT was re-trained after stroke while the protein synthesis inhibitor anisomycin (ANI) or saline were injected into the peri-infarct cortex through implanted cannulas. ANI injections reduced protein synthesis within the peri-infarct cortex by 69% and significantly impaired recovery of reaching performance through re-training. Improvement of motor performance within a single training session remained intact, while improvement between training sessions was impaired. ANI injections did not affect infarct size. Thus, protein synthesis inhibition within the peri-infarct cortex impairs recovery of motor deficits after ischemic stroke by interfering with consolidation of motor memory between training sessions but not short-term improvements within one session.

Highlights

Survivors of ischemic stroke often suffer from motor deficits that recover during days or weeks either spontaneously and/or supported by rehabilitative training
De novo learning of the skilled reaching task critically depends on the integrity and functionality of the primary motor cortex [7, 12, 13], a brain region that is considered as the key structure where motor memories are stored under physiological conditions [2, 12, 14]
Rats are able to regain reaching performance, a process that is supported by continuously practicing the skilled-reaching task (SRT) as a rehabilitative training [15, 16]

Summary

Introduction

Survivors of ischemic stroke often suffer from motor deficits that recover during days or weeks either spontaneously and/or supported by rehabilitative training. In human stroke-survivors, activation of cortical areas in the vicinity of the ischemic scar, the peri-infarct cortex is associated with a favorable outcome [1]. In rodent models of cortical ischemic stroke, profound structural changes such as axonal sprouting and formation of novel synapses are known to occur in the peri-infarct cortex [2]. These plastic changes critically depend on de novo synthesis of proteins [3, 4]. Protein synthesis inhibition (PSI) through systemic or local application of inhibitors of the peptidyl transferase (e.g. anisomycin, ANI) abolishes memory consolidation by preventing protein-synthesis dependent plastic processes. Acquisition of skilled reaching (SRT) is impaired by ANI-injection into the primary motor cortex [7]

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