TARGETING LSD1 TO REDUCE NEUROINFLAMMATION AND PROMOTE FUNCTIONAL RECOVERY AFTER SPINAL CORD INJURY

Spinal cord injury (SCI) remains a major cause of long-term disability, largely due to secondary damage processes such as neuroinflammation and glial reactivity that limit regeneration and functional recovery. Epigenetic regulation, particularly via lysine-specific demethylase 1A (LSD1), has emerged as a promising target to modulate these pathological responses. Here, we investigate the effects of LSD1 inhibition on neuroinflammatory processes using a pharmacological approach in vitro and in vivo.
Primary bone marrow-derived macrophages and astrocyte cultures were used to assess cell-specific responses to LSD1 inhibition. Pharmacological treatment with a LSD1 inhibitor, led to a marked attenuation of pro-inflammatory responses in both cell types. In macrophages, LSD1 inhibition reduced pro-inflammatory cytokine expression and limited cell proliferation. In astrocytes, treatment decreased the acquisition of features associated with reactive states. In vivo, a controlled SCI was induced in mice followed by sustained administration of the LSD1 inhibitor. Electrophysiological analyses demonstrated improved motor conduction along descending motor pathways in treated animals. Consistent with these functional improvements, analysis of injured spinal cord tissue indicated glial reactivity and a partial restoration of tissue homeostatic support.
Together, these findings demonstrate that LSD1 inhibition can effectively reduce neuroinflammation and modulate key cellular responses after SCI. These insights advance our understanding of epigenetic regulation in neural trauma and support the development of innovative strategies to promote neural repair and functional recovery after spinal cord injury.