Protein Synthesis Inhibition in the Peri-Infarct Cortex Slows Motor Recovery in Rats.
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.
Division of Vascular Neurology and Rehabilitation, Department of Neurology, University and University Hospital of Zurich, Zurich, Switzerland.
Maximilian
M
Schubring-Giese
Division of Vascular Neurology and Rehabilitation, Department of Neurology, University and University Hospital of Zurich, Zurich, Switzerland.
Susan
S
Leemburg
Division of Vascular Neurology and Rehabilitation, Department of Neurology, University and University Hospital of Zurich, Zurich, Switzerland.|cereneo Center for Neurology and Rehabilitation, Vitznau, Switzerland.|Department of Neurology, Johns Hopkins University, 1550 Orleans Street, Baltimore, Maryland, 21231, United States of America.
Andreas Rüdiger
AR
Luft
Division of Vascular Neurology and Rehabilitation, Department of Neurology, University and University Hospital of Zurich, Zurich, Switzerland.
Jonas Aurel
JA
Hosp
D000818:Animals; D000841:Anisomycin / Q000008:administration & dosage; D004195:Disease Models, Animal; D005552:Forelimb / Q000187:drug effects / Q000503:physiopathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D009044:Motor Cortex / Q000187:drug effects / Q000503:physiopathology*; D009048:Motor Skills / Q000187:drug effects / Q000502:physiology*; D009415:Nerve Net / Q000187:drug effects / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D014176:Protein Biosynthesis / Q000187:drug effects; D051381:Rats; D020127:Recovery of Function; D020521:Stroke / Q000188:drug therapy* / Q000503:physiopathology; D000071939:Stroke Rehabilitation
D000841:Anisomycin