Microglia contributes to remyelination in cerebral but not spinal cord ischemia

• Published in: Glia 2021-11, Vol.69 (11), p.2739-2751
• Main Authors: Pavic, Goran, Petzsch, Patrick, Jansen, Robin, Raba, Katharina, Rychlik, Nicole, Simiantonakis, Ioannis, Küry, Patrick, Göttle, Peter, Köhrer, Karl, Hartung, Hans‐Peter, Meuth, Sven G., Jander, Sebastian, Gliem, Michael
• Format: Article
• Language: English
• Subjects: Brain; brain ischemia; Central nervous system; Cerebral cortex; Comparative studies; Compartments; Depletion; Flow cytometry; Humans; Immunology; Inflammation; Inflammatory response; Ischemia; Lesions; Macrophages; Macrophages - pathology; Microglia; Microglia - pathology; Monocytes; Myelination; photothrombosis; Remyelination; Spinal cord; Spinal Cord - pathology; Spinal cord injuries; Spinal Cord Injuries - pathology; spinal cord ischemia; Spinal Cord Ischemia - pathology; stroke; Substantia grisea; Therapeutic targets
• ISSN: 0894-1491; 1098-1136
• DOI: 10.1002/glia.24068

Inflammation after injury of the central nervous system (CNS) is increasingly viewed as a therapeutic target. However, comparative studies in different CNS compartments are sparse. To date only few studies based on immunohistochemical data and all referring to mechanical injury have directly compared inflammation in different CNS compartments. These studies revealed that inflammation is more pronounced in spinal cord than in brain. Therefore, it is unclear whether concepts and treatments established in the cerebral cortex can be transferred to spinal cord lesions and vice versa or whether immunological treatments must be adapted to different CNS compartments. By use of transcriptomic and flow cytometry analysis of equally sized photothrombotically induced lesions in the cerebral cortex and the spinal cord, we could document an overall comparable inflammatory reaction and repair activity in brain and spinal cord between day 1 and day 7 after ischemia. However, remyelination was increased after cerebral versus spinal cord ischemia which is in line with increased remyelination in gray matter in previous analyses and was accompanied by microglia dominated inflammation opposed to monocytes/macrophages dominated inflammation after spinal cord ischemia. Interestingly remyelination could be reduced by microglia and not hematogenous macrophage depletion. Our results show that despite different cellular composition of the postischemic infiltrate the inflammatory response in cerebral cortex and spinal cord are comparable between day 1 and day 7. A striking difference was higher remyelination capacity in the cerebral cortex, which seems to be supported by microglia dominance. Main Points Comparable inflammation and repair in brain and spinal cord from day 1 to 7 after ischemia. Microglia dominance in cerebral cortex and monocytes/macrophages dominance in spinal cord. Microglia dominance linked to remyelination capacity.