Midkine Overexpression Promotes Functional Recovery After Spinal Cord Injury by Enhancing Microglial Efferocytosis...

Area of Science:

• Neuroscience
• Regenerative Medicine
• Cell Biology

Background:

• Traumatic spinal cord injury (SCI) causes neuronal death and inflammation, impairing functional recovery.
• Efficient removal of apoptotic cells and control of neuroinflammation are crucial for spinal cord repair.

Purpose of the Study:

• To investigate if Midkine (MDK) improves functional recovery after SCI.
• To explore the underlying mechanisms of MDK's effects in SCI.

Main Methods:

• Established a rat model of moderate SCI.
• Utilized lentiviral vectors for MDK overexpression.
• Assessed motor function recovery through BBB scores, gait analysis, and motor evoked potentials (MEPs).
• Conducted in vivo and in vitro experiments to study microglial efferocytosis and molecular pathways.

Main Results:

• MDK overexpression significantly improved motor function, reduced neuroinflammation, decreased neuronal apoptosis, and enhanced neuroprotection.
• MDK promoted microglial efferocytosis, activated the AKT/mTOR pathway, and upregulated BDNF and LRP-1.
• MDK facilitated microglial polarization towards an anti-inflammatory M2 phenotype.
• LRP-1 was identified as a key mediator of MDK's efferocytic and neuroprotective effects.

Conclusions:

• The MDK/LRP-1/efferocytosis axis is a novel therapeutic target for SCI.
• MDK therapy can orchestrate apoptotic cell clearance, reduce neuroinflammation, and promote neuroprotection for spinal cord repair.
• Modulating LRP-1 offers precise control over microglial responses in SCI treatment.