J Neuroinflamm
-
Neuroinflammation is an essential player in many neurological diseases including traumatic brain injury (TBI). Recent studies have identified that inflammasome complexes are responsible for inflammatory responses in many pathological conditions. Inflammasomes are intracellular multiprotein complexes which regulate the innate immune response, activation of caspase-1, production of pro-inflammatory cytokines IL-1β and IL-18, and induction of cell death (pyroptosis). Among inflammasome family members, the nucleotide-binding domain leucine-rich repeats family protein 3 (NLRP3) is the most extensively studied and its activation is induced following TBI. As a novel target, drug development targeting the formation and activation of NLRP3 inflammasome is a prospective therapy for TBI. We have recently developed a small molecule JC124 with specificity on NLRP3 inflammasome. In this study, we explored the therapeutic value of JC124 for TBI treatment. ⋯ Our data suggest that our novel NLRP3 inhibitor has a specific anti-inflammatory effect to protect the injured brain following TBI.
-
Neuropathic pain is caused by sensory nerve injury, but effective treatments are currently lacking. Microglia are activated in the spinal dorsal horn after sensory nerve injury and contribute to neuropathic pain. Accordingly, molecules expressed by these cells are considered potential targets for therapeutic strategies. Our previous gene screening study using a mouse model of motor nerve injury showed that the G-protein-coupled receptor 34 gene (GPR34) is induced by nerve injury. Because GPR34 is now considered a microglia-enriched gene, we explored the possibility that it might be involved in microglial activation in the dorsal horn in a mouse model of neuropathic pain. ⋯ Inhibition of GPR34-mediated signal by GPR34 gene deletion reduced nerve injury-induced neuropathic pain by suppressing pro-inflammatory responses of microglia without affecting their morphology. Therefore, the suppression of GPR34 activity may have therapeutic potential for alleviating neuropathic pain.
-
Activation of microglial cells plays an important role in neuroinflammation after ischemic stroke. Inhibiting the activation of microglial cells has been suggested as a potential therapeutic approach in the treatment of ischemic stroke. ⋯ LncRNA-1810034E14Rik plays an anti-inflammatory role in ischemic stroke and regulates p65 phosphorylation, making it a potential target for stroke treatment.