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  4. The Rho-associated kinase inhibitors Y27632 and fasudil promote microglial migration in the spinal cord via the ERK signaling pathway

The Rho-associated kinase inhibitors Y27632 and fasudil promote microglial migration in the spinal cord via the ERK signaling pathway

Neural Regeneration Research, 2018 · DOI: 10.4103/1673-5374.230294 · Published: April 1, 2018

Spinal Cord InjuryNeurologyGenetics

Simple Explanation

Microglia, the main immune cells in the central nervous system, gather at injury sites and can both worsen and improve tissue damage after spinal cord injury. The study explores how inhibiting Rho-associated kinase (ROCK), an enzyme involved in inflammation, affects microglial migration, which is important for tissue repair. The research focuses on the impact of ROCK inhibitors Y27632 and fasudil on microglial movement and the mechanisms behind it. The researchers found that Y27632 and fasudil increased microglial migration and altered their shape, making them irregular with many small processes. These drugs also increased levels of phosphorylated ERK protein, a key component of a signaling pathway involved in cell growth and migration. Blocking the ERK pathway with U0126 reversed the effects of Y27632 and fasudil. The findings suggest that ROCK inhibitors Y27632 and fasudil promote microglial migration in the spinal cord through the ERK signaling pathway. By enhancing microglial migration, these inhibitors could potentially improve tissue remodeling and functional recovery after spinal cord injury.

Study Duration
Not specified
Participants
Primary cultured microglia isolated from the spinal cord of newborn Sprague-Dawley pups
Evidence Level
Level III, experimental study

Key Findings

  • 1
    Y27632 and fasudil increased microglial migration, suggesting ROCK inhibition promotes microglial motility.
  • 2
    ROCK inhibitors altered microglial morphology, leading to larger, irregularly shaped cells with more processes.
  • 3
    The ERK signaling pathway mediates the effects of Y27632 and fasudil on microglial migration and morphology, as blocking ERK with U0126 reversed these effects.

Research Summary

This study investigates the effect of ROCK inhibitors, Y27632 and fasudil, on microglial migration in the spinal cord and the underlying mechanisms. The researchers found that these inhibitors promote microglial migration and alter cell morphology through the ERK signaling pathway. The study demonstrates that Y27632 and fasudil increase microglial migration and upregulate phosphorylated ERK protein levels. Furthermore, the ERK inhibitor U0126 suppressed the effects of Y27632 and fasudil, indicating the involvement of the ERK signaling pathway. The findings suggest that ROCK inhibitors promote microglial migration in the spinal cord via the ERK signaling pathway, which may contribute to functional recovery after spinal cord injury.

Practical Implications

Therapeutic Target for SCI

The Rho/ROCK signaling pathway is a potential therapeutic target for spinal cord injury (SCI) treatment due to its involvement in microglial phagocytosis and migration.

Clinical Translation

Fasudil, already used clinically for ischemic cerebrovascular disease, could be considered for clinical trials in SCI treatment.

Drug Development

Further research into the molecular mechanisms underlying the role of ROCK in spinal cord injury could lead to the development of new drugs.

Study Limitations

  • 1
    The study was conducted in vitro using primary cultured microglia, which may not fully reflect the complex in vivo environment.
  • 2
    The specific downstream targets of the ERK signaling pathway in microglial migration were not fully elucidated.
  • 3
    The long-term effects of ROCK inhibition on microglial function and spinal cord recovery were not investigated.

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