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In Situ Visualization of Axon Growth and Growth Cone Dynamics in Acute Ex Vivo Embryonic Brain Slice Cultures
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Diltiazem Promotes Regenerative Axon Growth
Eric A Huebner1,2, Stéphane Budel2, Zhaoxin Jiang2
1F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
Molecular Neurobiology
|September 21, 2018
Summary
Researchers screened compounds to find drugs that help regenerate axons after central nervous system (CNS) injury. Diltiazem, verapamil, and bromopride showed promise in promoting axon regrowth in damaged neurons.
Area of Science:
- Neuroscience
- Regenerative Medicine
- Pharmacology
Background:
- Adult central nervous system (CNS) injuries cause permanent function loss due to limited nerve regeneration.
- Chondroitin sulfate proteoglycans (CSPGs) inhibit axon regrowth in the CNS.
Purpose of the Study:
- To identify pharmacological compounds that enhance axon regeneration.
- To investigate potential treatments for CNS injuries.
Main Methods:
- Screened 960 compounds for their ability to promote cortical neuron axonal regrowth.
- Utilized an in vitro cortical scrape assay.
- Tested promising compounds on rat cortical cultures and mouse dorsal root ganglion (DRG) neurons.
Main Results:
- Diltiazem, verapamil, and bromopride were identified as facilitators of axon regeneration.
- Diltiazem, an L-type calcium channel blocker (L-CCB), demonstrated axon outgrowth promotion in rat cortical cultures, iSensory neurons, and adult primary mouse DRG neurons, even with CSPGs present.
Conclusions:
- Diltiazem, verapamil, and bromopride represent potential therapeutic agents for promoting CNS axon regeneration.
- L-type calcium channel blockers show promise in overcoming inhibitory molecules like CSPGs to enhance neural repair.
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