Neuronal apoptosis suppression and efficient apoptotic cell clearance are crucial for preventing secondary spinal cord injury (SCI). The immunoreceptor CD300a is a phosphatidylserine receptor expressed on myeloid cells that modulates secondary neuronal damage by regulating efferocytosis. CD300a blockade has previously enhanced efferocytosis and improved neurological deficits in an ischemic stroke mouse model. However, the mechanisms and roles of CD300a in acute SCI remain unclear. Therefore, we evaluated the effects of CD300a regulation on acute SCI. First, an SCI model was created in CD300a-deficient mice and compared with that in wild-type mice. Second, we compared the effects of treating wild-type mice with anti-CD300a or control antibodies. The effects were evaluated over 6 weeks by analyzing behavioral outcomes using the Basso Mouse Scale and injured spinal cord tissue. Damage-associated molecular patterns (DAMPs) were evaluated in the acute phase, and oligodendrocyte apoptosis was assessed in the subacute phase of SCI to assess the effects of CD300a on inflammation and secondary injury. CD300a-deficient mice exhibited improved motor function, a reduced lesion area, and an increased residual myelin area. Immunohistochemical staining revealed reduced scarring and more surviving neurons. CD300a-deficient mice exhibited decreased extracellular DAMPs and oligodendrocyte apoptosis in the acute and subacute phases, respectively. The antibody-treated group also exhibited improved motor function, reduced lesion area, and increased residual myelin. These findings suggest that CD300a regulation mitigates SCI by suppressing DAMP release and apoptosis, thereby contributing to reduced tissue damage and functional recovery. These findings highlight CD300a regulation as a potentially effective treatment for acute SCI.
Okuwaki et al. (Tue,) studied this question.