Microglia-Astrocyte communication through spinal cord injury

 Understanding the mechanisms of inflammation and glial scar formation after spinal cord injury (SCI) is not possible without the comprehension of reactive astrocytes and resident microglia activation, and the infiltration of macrophages in the major pathogenesis of SCI. Early after SCI, both the microglia and astrocytes are activated into two polarization states: the pro-inflammatory phenotypes (M1 and A1) and the anti-inflammatory phenotypes (M2 and A2). This fact plays an important role in the regulation of immune responses under various pathological conditions and repair. We aimed to study the behavior of reactive astrocytes and microglia/macrophages and their polarization states after Th9 compression (40g/15 min) at the lesion site and in adjacent spinal cord sections. Adult Wistar rats were divided into three experimental groups: 1) sham control, and 2-3) a group of animals that survived 7 and 14 days after SCI. The results show that microglia/macrophages and astrocytes transformation after Th9 compression is mostly impacted at the lesion site and 3 mm caudally from the injury epicenter. While the gene expression of reactive microglia/macrophages was strongly upregulated one week after SCI in each segment studied, reactive astrocytes were considerably expressed two weeks post-injury. The study of particular phenotypes indicates that the first post-injury week is critical for the modulation of reactive microglia/astrocytes into their neuroprotective states and that inhibiting M1/A1 and/or promoting M2/A2 polarization may be a very effective treatment strategy to improve functional recovery after SCI. Supported by APVV-15-0766; APVV-19-0324; VEGA 2/0145/21; VEGA 2/0098/20; ERDF-IMTS 313011V344