title: Anti-neuroinflammatory effects of the calcium channel blocker nicardipine on microglial cells: implications for neuroprotection.
abstract: OBJECTIVE
  Nicardipine is a calcium channel blocker that has been widely used to control blood pressure in severe hypertension following events such as ischemic stroke, traumatic brain injury, and intracerebral hemorrhage. However, accumulating evidence suggests that inflammatory processes in the central nervous system that are mediated by microglial activation play important roles in neurodegeneration, and the effect of nicardipine on microglial activation remains unresolved.
  
  
  RESULTS
  In the present study, using murine BV-2 microglia, we demonstrated that nicardipine significantly inhibits microglia-related neuroinflammatory responses. Treatment with nicardipine inhibited microglial cell migration. Nicardipine also significantly inhibited LPS plus IFN-γ-induced release of nitric oxide (NO), and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, nicardipine also inhibited microglial activation by peptidoglycan, the major component of the Gram-positive bacterium cell wall. Notably, nicardipine also showed significant anti-neuroinflammatory effects on microglial activation in mice in vivo.
  
  
  CONCLUSIONS
  The present study is the first to report a novel inhibitory role of nicardipine on neuroinflammation and provides a new candidate agent for the development of therapies for inflammation-related neurodegenerative diseases.
authors.affiliation: Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan; Neurosurgery Department, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan; School of Medicine, Tzu Chi University, Hualien, Taiwan.
authors.forename: Bor-Ren
authors.initials: BR
authors.lastname: Huang
authors.affiliation: Department of Bioinformatics, Asia University, Taichung, Taiwan.
authors.forename: Pei-Chun
authors.initials: PC
authors.lastname: Chang
authors.affiliation: Department of Cell and Tissue Engineering, Changhua Christian Hospital, Changhua, Taiwan.
authors.forename: Wei-Lan
authors.initials: WL
authors.lastname: Yeh
authors.affiliation: Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, United States of America.
authors.forename: Chih-Hao
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Department of Biotechnology, Asia University, Taichung, Taiwan.
authors.forename: Cheng-Fang
authors.initials: CF
authors.lastname: Tsai
authors.affiliation: Department of Physiology, School of Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Chingju
authors.initials: C
authors.lastname: Lin
authors.affiliation: Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Hsiao-Yun
authors.initials: HY
authors.lastname: Lin
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
authors.forename: Yu-Shu
authors.initials: YS
authors.lastname: Liu
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
authors.forename: Caren Yu-Ju
authors.initials: CY
authors.lastname: Wu
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan.
authors.forename: Pei-Ying
authors.initials: PY
authors.lastname: Ko
authors.affiliation: Department of Pharmacology and Institute of Medicine, College of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Shiang-Suo
authors.initials: SS
authors.lastname: Huang
authors.affiliation: Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan; Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Horng-Chaung
authors.initials: HC
authors.lastname: Hsu
authors.affiliation: Graduate Institute of Neural and Cognitive Sciences, China Medical University, Taichung, Taiwan.
authors.forename: Dah-Yuu
authors.initials: DY
authors.lastname: Lu
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D009529:Nicardipine / Q000494:pharmacology* / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D002121:Calcium Channel Blockers; D016207:Cytokines; D018696:Neuroprotective Agents; D009529:Nicardipine