Modulation of inflammatory and regenerative responses by Galectin-3 after spinal cord injury in wild-type and...

Spinal cord injury (SCI) occurs either after a sudden trauma or through a chronic process at segmental levels of the spinal cord, leading to potentially deleterious neural consequences for the central nervous system (CNS) due to the death of neurons, oligodendrocytes, and astrocytes, as well as significant losses in motor, sensory, and autonomic functions. After SCI, an inflammatory response occurs, with cells such as macrophages and microglia being recruited. These cells are responsible for removing damaged tissue and secreting pro-inflammatory and anti-inflammatory cytokines and chemokines. Additionally, a protein called galectin-3 has been described as participating in cell activation, proliferation, and migration, acting as a mediator of inflammation in neurodegeneration. Thus, different populations of inflammatory cells in the injured nervous parenchyma can be characterized. In this study, we used a spinal cord contusion-compression model in wild-type C57Bl/6 mice (WT) and galectin-3 knockout mice (GAL3-/-) to histologically characterize the lesion, focusing on astrocyte, macrophage, and microglial populations. Our results showed a significant reduction in lesion propagation in GAL3-/- animals compared to WT animals. Moreover, GAL3-/- animals exhibited reduced astrogliosis compared to WT animals. Immunohistochemistry revealed that GAL3-/- animals had a larger area marked for the anti-inflammatory marker Arginase-1 and a smaller area marked for the pro-inflammatory marker iNOS compared to WT animals. We conclude that galectin-3 plays a critical role in the inflammatory process following spinal cord injury, and its absence may contribute to reduced lesion progression, decreased astrogliosis, and the promotion of an inflammatory response with a more anti-inflammatory profile. SIGNIFICANCE STATEMENT: This study highlights galectin-3 as a central mediator of the inflammatory response after spinal cord injury, demonstrating that galectin-3 deficiency limits lesion progression, attenuates astrogliosis, and promotes an anti-inflammatory profile. Thus, galectin-3 may represent a promising potential therapeutic target for clinical applications in neurodegenerative diseases.