Drug screening in zebrafish larvae reveals inflammation-related modulators of secondary damage after spinal cord injury in mice

Spinal cord injury (SCI) in humans can lead to permanent loss of sensory and motor functions, due to wide-spread tissue damage and insufficient repair. Primary tissue damage is caused directly by the impact, and secondary damage that occurs over a wider area ensues as a consequence of the break-down of the blood-spinal cord barrier. This is often accompanied by chronic inflammation. Researchers screened drugs in zebrafish larvae to find compounds that reduce inflammation, then tested promising drugs in a mouse model of spinal cord injury. They found that Cimetidine, a common drug, reduced inflammation and improved recovery in both zebrafish and mice with spinal cord injuries. This study suggests that targeting histamine receptors with drugs like Cimetidine could be a new way to treat spinal cord injuries in humans. The zebrafish model is a useful tool for quickly finding potential treatments for SCI.

• 1
  Cimetidine, an over-the-counter H2 receptor antagonist, reduced il-1β expression in zebrafish and partially rescued impaired regeneration in the irf8 zebrafish mutant model for chronic inflammation.
• 2
  In mice, systemic treatment with Cimetidine led to significantly improved recovery of locomotor behavior as compared to controls, accompanied by decreased neuronal tissue loss and a shift towards a pro-regenerative profile of cytokine gene expression.
• 3
  Somatic mutation of hrh2b did not affect overall development of larvae (eye size, body length; Figure S4A-F) or recovery of axon bridging (Figure S4G-H).