J Neuroinflamm
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The interaction between the membrane glycoprotein, CD200 and its cognate receptor CD200 receptor (CD200R), has been shown to play a role in maintaining microglia in a quiescent state. There is evidence of increased activation under resting and stimulated conditions in microglia prepared from CD200-deficient mice compared with wild-type mice, whereas activation of the receptor by CD200 fusion protein (CD200Fc) ameliorates inflammatory changes which are evident in the central nervous system (CNS) of the mouse model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE) and also in the hippocampus of aged rats. Additionally, an inverse relationship between microglial activation and expression of CD200 has been observed in animals treated with lipopolysaccharide (LPS) or amyloid-β (Aβ). ⋯ The findings suggest that activation of CD200R and Dok2 is a valuable strategy for modulating microglial activation and may have therapeutic potential in neurodegenerative conditions.
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Traumatic brain injury (TBI) induces activation of microglia. Activated microglia can in turn increase secondary injury and impair recovery. This innate immune response requires hours to days to become fully manifest, thus providing a clinically relevant window of opportunity for therapeutic intervention. Microglial activation is regulated in part by poly(ADP-ribose) polymerase-1 (PARP-1). Inhibition of PARP-1 activity suppresses NF-kB-dependent gene transcription and thereby blocks several aspects of microglial activation. Here we evaluated the efficacy of a PARP inhibitor, INO-1001, in suppressing microglial activation after cortical impact in the rat. ⋯ Treatment with a PARP inhibitor for 12 days after TBI, with the first dose given as long as 20 hours after injury, can reduce inflammation and improve histological and functional outcomes.
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The kinin B(1) receptor (B(1)R) is upregulated by pro-inflammatory cytokines and oxydative stress, which are enhanced by transient receptor potential vanilloid subtype 1 (TRPV1) activation. To examine the link between TRPV1 and B(1)R in inflammatory pain, this study aimed to determine the ability of TRPV1 to regulate microglial B(1)R expression in the spinal cord dorsal horn, and the underlying mechanism. ⋯ This study highlights a new mechanism for B(1)R induction via TRPV1 activation and establishes a link between these two pro-nociceptive receptors in inflammatory pain.
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The neuroinflammatory responses in the spinal cord following bone cancer development have been shown to play an important role in cancer-induced bone pain (CIBP). Lipoxins (LXs), endogenous lipoxygenase-derived eicosanoids, represent a unique class of lipid mediators that possess a wide spectrum of anti-inflammatory and pro-resolving actions. In this study, we investigated the effects of intrathecal injection with lipoxin and related analogues on CIBP in rats. ⋯ Taken together, the results of our study suggest that LXs and analogues exert strong analgesic effects on CIBP. These analgesic effects in CIBP are associated with suppressing the expression of spinal proinflammatory cytokines.
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Neuropathic pain in the trigeminal system is frequently observed in clinic, but the mechanisms involved are largely unknown. In addition, the function of immune cells and related chemicals in the mechanism of pain has been recognized, whereas few studies have addressed the potential role of chemokines in the trigeminal system in chronic pain. The present study was undertaken to test the hypothesis that chemokine C-C motif ligand 2 (CCL2)-chemokine C-C motif receptor 2 (CCR2) signaling in the trigeminal nucleus is involved in the maintenance of trigeminal neuropathic pain. ⋯ The data suggest that CCL2-CCR2 signaling may be involved in the maintenance of orofacial neuropathic pain via astroglial-neuronal interaction. Targeting CCL2-CCR2 signaling may be a potentially important new treatment strategy for trigeminal neuralgia.