The Spinal Transcriptome after Cortical Stroke: In Search of Molecular Factors Regulating Spontaneous Recovery in the Spinal Cord
Autor: | Vladimir B.C. de Souza, Mark D. Robinson, Martin E. Schwab, Martina A. Maibach, Julia Kaiser, Niels Hagenbuch, Iris Salpeter |
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Přispěvatelé: | University of Zurich, Kaiser, Julia |
Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Male Plasticity Recovery Regeneration Spinal cord Stroke Transcriptome Neurite Development/Plasticity/Repair Pyramidal Tracts Biology Grey matter 03 medical and health sciences Mice 0302 clinical medicine medicine Animals RNA Messenger Gray Matter Research Articles Cerebral Cortex Inflammation Phagocytes Microglia General Neuroscience Motor Cortex Computational Biology 2800 General Neuroscience Recovery of Function Macrophage Activation medicine.disease 10124 Institute of Molecular Life Sciences Nerve Regeneration Mice Inbred C57BL Anterograde tracing 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation Corticospinal tract 570 Life sciences biology Female Neuroscience 030217 neurology & neurosurgery Motor cortex |
Zdroj: | The Journal of Neuroscience, 39 (24) The Journal of Neuroscience |
ISSN: | 0270-6474 1529-2401 |
DOI: | 10.3929/ethz-b-000349770 |
Popis: | In response to cortical stroke and unilateral corticospinal tract degeneration, compensatory sprouting of spared corticospinal fibers is associated with recovery of skilled movement in rodents. To date, little is known about the molecular mechanisms orchestrating this spontaneous rewiring. In this study, we provide insights into the molecular changes in the spinal cord tissue after large ischemic cortical injury in adult female mice, with a focus on factors that might influence the reinnervation process by contralesional corticospinal neurons. We mapped the area of cervical gray matter reinnervation by sprouting contralesional corticospinal axons after unilateral photothrombotic stroke of the motor cortex in mice using anterograde tracing. The mRNA profile of this reinnervation area was analyzed using whole-genome sequencing to identify differentially expressed genes at selected time points during the recovery process. Bioinformatic analysis revealed two phases of processes: early after stroke (4–7 d post-injury), the spinal transcriptome is characterized by inflammatory processes, including phagocytic processes as well as complement cascade activation. Microglia are specifically activated in the denervated corticospinal projection fields in this early phase. In a later phase (28–42 d post-injury), biological processes include tissue repair pathways with upregulated genes related to neurite outgrowth. Thus, the stroke-denervated spinal gray matter, in particular its intermediate laminae, represents a growth-promoting environment for sprouting corticospinal fibers originating from the contralesional motor cortex. This dataset provides a solid starting point for future studies addressing key elements of the post-stroke recovery process, with the goal to improve neuroregenerative treatment options for stroke patients. The Journal of Neuroscience, 39 (24) ISSN:0270-6474 ISSN:1529-2401 |
Databáze: | OpenAIRE |
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