Journal Article

Anti-Neuroinflammatory Effects of the Calcium Channel Blocker Nicardipine on Microglial Cells: Implications for Neuroprotection

Lu, Dah-Yuu, Hsu, Horng-Chaung, Huang, Shiang-Suo, Yeh, Wei-Lan, Chang, Pei-Chun, Wu, Caren Yu-Ju, Lin, Chingju, Liu, Yu-Shu, Tsai, Cheng-Fang, Lin, Hsiao-Yun, Lee, Chih-Hao, Ko, Pei-Ying, Huang, Bor-Ren

2014

Overview

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. 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. 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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Activation / Alzheimer's disease / Alzheimers disease / Analysis / Animals / Biology / Biotechnology / Blood pressure / Blood Pressure - drug effects / Bone surgery / Brain / Brain injuries / Calcium / Calcium Channel Blockers - pharmacology / Calcium Channel Blockers - therapeutic use / Calcium channels / Cell Line / Cell migration / Cell walls / Central nervous system / COX-2 inhibitors / Cyclooxygenase-2 / Cytokines - metabolism / Gene Expression Regulation - drug effects / Head injuries / Hemorrhage / Hospitals / Hypertension / Hypoxia / Immunoglobulins / In vivo methods and tests / Inflammation / Inflammation - drug therapy / Inflammation - metabolism / Inflammation - pathology / Inflammation - physiopathology / Inhibition / Interferon / Ischemia / Kinases / Laboratory animals / Lipopolysaccharides / Medicine / Mice / Microglia / Microglia - drug effects / Microglia - metabolism / Microglia - pathology / Microglial cells / Nervous system / Nervous system diseases / Neurodegeneration / Neurodegenerative diseases / Neurological diseases / Neuroprotection / Neuroprotective Agents - pharmacology / Neuroprotective Agents - therapeutic use / Nicardipine - pharmacology / Nicardipine - therapeutic use / Nitric oxide / Nitric-oxide synthase / Peptidoglycans / Rodents / Science / Signal Transduction - drug effects / Stroke / Studies / Traumatic brain injury / γ-Interferon