Ganoderma microsporum–derived fungal immunomodulatory protein (GMI) promotes functional recovery after spinal cord injury by modulating anti-inflammation and enhancing regeneration

Spinal cord injury (SCI) causes devastating damage to the central nervous system (CNS). Ganoderma microsporum-derived immunomodulatory protein (GMI) is known for its potent anti-inflammatory and antitumor activities in various preclinical models. However, its effects and underlying mechanisms in CNS injury remain largely unexplored. In a SCI rat model, intravenous administration of GMI reduces histopathological alterations in the spinal cord and improves hindlimb motor functions. At eight weeks post-injury, GMI-treated rats exhibited restored neural morphology, enhanced neurogenesis and reduced glial scarring in the injured spinal cord. During the subacute phase of SCI, GMI accumulates at the lesion site, where it suppresses microglial activation and reduces the number of IL-1β–positive cells. Moreover, GMI attenuates the LPS/IFN-γ- induced inflammatory responses in both microglia cells and neuron/glial cultures. It also downregulates the expressions of CD80 and CD86 in IFN-γ-stimulated microglia cells. This study is the first to demonstrate the therapeutic potential of GMI following SCI, highlighting it as a promising candidate for SCI treatment.