PMID- 30232777 OWN - NLM STAT- MEDLINE DCOM- 20190829 LR - 20210109 IS - 1559-1182 (Electronic) IS - 0893-7648 (Print) IS - 0893-7648 (Linking) VI - 56 IP - 6 DP - 2019 Jun TI - Diltiazem Promotes Regenerative Axon Growth. PG - 3948-3957 LID - 10.1007/s12035-018-1349-5 [doi] AB - Axotomy results in permanent loss of function after brain and spinal cord injuries due to the minimal regenerative propensity of the adult central nervous system (CNS). To identify pharmacological enhancers of axon regeneration, 960 compounds were screened for cortical neuron axonal regrowth using an in vitro cortical scrape assay. Diltiazem, verapamil, and bromopride were discovered to facilitate axon regeneration in rat cortical cultures, in the presence of chondroitin sulfate proteoglycans (CSPGs). Diltiazem, an L-type calcium channel blocker (L-CCB), also promotes axon outgrowth in adult primary mouse dorsal root ganglion (DRG) and induced human sensory (iSensory) neurons. FAU - Huebner, Eric A AU - Huebner EA AD - F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, MA, 02115, USA. AD - Cellular Neuroscience, Neurodegeneration and Repair Program, Departments of Neurology and Neuroscience, Yale University School of Medicine, New Haven, CT, 06520, USA. FAU - Budel, Stephane AU - Budel S AD - Cellular Neuroscience, Neurodegeneration and Repair Program, Departments of Neurology and Neuroscience, Yale University School of Medicine, New Haven, CT, 06520, USA. FAU - Jiang, Zhaoxin AU - Jiang Z AD - Cellular Neuroscience, Neurodegeneration and Repair Program, Departments of Neurology and Neuroscience, Yale University School of Medicine, New Haven, CT, 06520, USA. FAU - Omura, Takao AU - Omura T AD - F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, MA, 02115, USA. FAU - Ho, Tammy Szu-Yu AU - Ho TS AD - F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, MA, 02115, USA. FAU - Barrett, Lee AU - Barrett L AD - F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, MA, 02115, USA. FAU - Merkel, Janie S AU - Merkel JS AD - Yale Center for Molecular Discovery, Yale University, West Haven, CT, 06516, USA. FAU - Pereira, Luis M AU - Pereira LM AD - Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital and Harvard Medical School, Boston, MA, 02115, USA. FAU - Andrews, Nick A AU - Andrews NA AD - F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, MA, 02115, USA. FAU - Wang, Xingxing AU - Wang X AD - Cellular Neuroscience, Neurodegeneration and Repair Program, Departments of Neurology and Neuroscience, Yale University School of Medicine, New Haven, CT, 06520, USA. FAU - Singh, Bhagat AU - Singh B AD - F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, MA, 02115, USA. FAU - Kapur, Kush AU - Kapur K AD - F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, MA, 02115, USA. FAU - Costigan, Michael AU - Costigan M AD - F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, MA, 02115, USA. AD - Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital and Harvard Medical School, Boston, MA, 02115, USA. FAU - Strittmatter, Stephen M AU - Strittmatter SM AD - Cellular Neuroscience, Neurodegeneration and Repair Program, Departments of Neurology and Neuroscience, Yale University School of Medicine, New Haven, CT, 06520, USA. stephen.strittmatter@yale.edu. FAU - Woolf, Clifford J AU - Woolf CJ AUID- ORCID: 0000-0001-9840-596X AD - F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, MA, 02115, USA. clifford.woolf@childrens.harvard.edu. LA - eng GR - U01 EY027256/EY/NEI NIH HHS/United States GR - R01 NS042304/NS/NINDS NIH HHS/United States GR - T32 GM007205/GM/NIGMS NIH HHS/United States GR - R01 NS033020/NS/NINDS NIH HHS/United States GR - R01 NS039962/NS/NINDS NIH HHS/United States GR - UL1 TR001102/TR/NCATS NIH HHS/United States GR - T32 NS007473/NS/NINDS NIH HHS/United States GR - R35 NS097283/NS/NINDS NIH HHS/United States PT - Journal Article DEP - 20180919 PL - United States TA - Mol Neurobiol JT - Molecular neurobiology JID - 8900963 RN - 0 (Amides) RN - 0 (Calcium Channel Blockers) RN - 0 (Calcium Channels, L-Type) RN - 0 (Chondroitin Sulfate Proteoglycans) RN - 0 (Pyridines) RN - 138381-45-0 (Y 27632) RN - EE92BBP03H (Diltiazem) SB - IM MH - Amides/pharmacology MH - Animals MH - Axons/drug effects/*physiology MH - Calcium Channel Blockers/pharmacology MH - Calcium Channels, L-Type/metabolism MH - Chondroitin Sulfate Proteoglycans/metabolism MH - Diltiazem/*pharmacology MH - Drug Synergism MH - Ganglia, Spinal/drug effects/metabolism MH - Humans MH - Mice, Inbred C57BL MH - Nerve Regeneration/*drug effects MH - Pyridines/pharmacology MH - Rats, Sprague-Dawley PMC - PMC6424671 MID - NIHMS1507586 OTO - NOTNLM OT - Axon regeneration OT - Chondroitin sulfate proteoglycans OT - Cortical neurons OT - Diltiazem OT - Scrape assay OT - Sensory neurons COIS- Conflict of Interest: The authors declare that they have no conflict of interest. EDAT- 2018/09/21 06:00 MHDA- 2019/08/30 06:00 PMCR- 2020/06/01 CRDT- 2018/09/21 06:00 PHST- 2018/06/18 00:00 [received] PHST- 2018/09/11 00:00 [accepted] PHST- 2018/09/21 06:00 [pubmed] PHST- 2019/08/30 06:00 [medline] PHST- 2018/09/21 06:00 [entrez] PHST- 2020/06/01 00:00 [pmc-release] AID - 10.1007/s12035-018-1349-5 [pii] AID - 10.1007/s12035-018-1349-5 [doi] PST - ppublish SO - Mol Neurobiol. 2019 Jun;56(6):3948-3957. doi: 10.1007/s12035-018-1349-5. Epub 2018 Sep 19.