Abstract
Background/ObjectiveNicardipine 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.Methodology/Principal FindingsIn 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.Conclusion/SignificanceThe 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.
Highlights
Microglia play pivotal roles in host defense and tissue repair processes in the central nervous system [1]
Nicardipine suppresses neuroinflammatory responses in microglial cells We used BV-2 microglia to study the effects of nicardipine on neuroinflammatory responses
Nicardipine inhibited an ATP-induced increase in BV-2 microglial migratory activity (Fig. 1B)
Summary
Microglia play pivotal roles in host defense and tissue repair processes in the central nervous system [1]. Neuroinflammation caused by microglial activation have both beneficial and detrimental consequences in the nervous system [2,3]. Microglial activation involves changes in cell morphology and the subsequent expression of new proteins, such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). These proinflammatory cytokines have been shown to cause neuronal damage [13,14,15,16]. Inflammatory mediators are necessary for normal neuronal cell functions, the microglial response must be tightly regulated to avoid over-activation and neurotoxic consequences [24]
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