Tofacitinib Promotes Functional Recovery after Spinal Cord Injury by Regulating Microglial Polarization via JAK/STAT...

Area of Science:

• Neuroscience
• Immunology
• Pharmacology

Background:

• The JAK/STAT pathway is central to inflammation and its role in spinal cord injury (SCI) pathology requires further investigation.
• Targeting this pathway may offer a therapeutic strategy for SCI.
• The efficacy of pan-JAK inhibitors like tofacitinib (TOF) in SCI is explored.

Purpose of the Study:

• To investigate the therapeutic potential of tofacitinib (TOF) in mitigating secondary injury following spinal cord injury (SCI).
• To elucidate the underlying mechanisms by which TOF exerts its therapeutic effects in SCI.
• To evaluate the impact of TOF on neuroinflammation and neuronal survival post-SCI.

Main Methods:

• Establishment of an SCI rat model for in vivo evaluation of TOF treatment.
• Histological and behavioral analyses were conducted at various time points post-SCI.
• In vitro studies utilized primary microglia, BV2 cells, and co-cultures to assess TOF's effects on microglial activation, inflammation, and neuroprotection using western blot, qPCR, flow cytometry, and fluorescent staining.

Main Results:

• Tofacitinib (TOF) significantly improved motor dysfunction in rats with SCI.
• Early-stage TOF administration reduced neuronal apoptosis, inhibited scar formation, and promoted axonal and nerve fiber repair.
• TOF suppressed SCI-induced inflammation by inhibiting microglial activation in vivo and in vitro, demonstrating notable neuroprotective effects in vitro.

Conclusions:

• Tofacitinib (TOF) effectively regulates microglial activation through the JAK/STAT pathway, promoting motor function recovery after SCI.
• These findings underscore the significance of TOF as a potential immunotherapy for spinal cord injury.
• TOF demonstrates dual benefits of anti-inflammation and neuroprotection in the context of SCI.