J Neuroinflamm
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Randomized Controlled Trial Multicenter Study
The effect of intravenous interleukin-1 receptor antagonist on inflammatory mediators in cerebrospinal fluid after subarachnoid haemorrhage: a phase II randomised controlled trial.
Interleukin-1 (IL-1) is a key mediator of ischaemic brain injury induced by stroke and subarachnoid haemorrhage (SAH). IL-1 receptor antagonist (IL-1Ra) limits brain injury in experimental stroke and reduces plasma inflammatory mediators associated with poor outcome in ischaemic stroke patients. Intravenous (IV) IL-1Ra crosses the blood-brain barrier (BBB) in patients with SAH, to achieve cerebrospinal fluid (CSF) concentrations that are neuroprotective in rats. ⋯ IL-1Ra appears safe in SAH patients. The concentration of IL-6 was lowered to the degree expected, in both CSF and plasma for patients treated with IL-1Ra.
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Spinal cord injuries remain a critical issue in experimental and clinical research nowadays, and it is now well accepted that the immune response and subsequent inflammatory reactions are of significant importance in regulating the damage/repair balance after injury. The role of macrophages in such nervous system lesions now becomes clearer and their contribution in the wound healing process has been largely described in the last few years. ⋯ Indeed, recent data show that neutrophils are required for promoting functional recovery after spinal cord trauma. In this review, we gathered recent evidence concerning the role of neutrophils in spinal cord injuries but also in some other neurological diseases, highlighting the need for further understanding the different mechanisms involved in spinal cord injury and repair.
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The immune system response and inflammation play a key role in brain injury during and after a stroke. The acute immune response is responsible for secondary brain tissue damage immediately after the stroke, followed by immunosuppression due to sympathetic nervous system activation. ⋯ The pneumonia-related inflammatory state can release a bystander autoimmune response against central nervous system antigens, thereby initiating a vicious circle. The aim of this review is to summarize the relationship between ischemic stroke, sympathetic nervous system activation and pulmonary infection.
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Visual prognosis after an open globe injury is typically worse than after a closed globe injury due, in part, to the immune response that ensues following open globe trauma. There is a need for an animal model of open globe injury in order to investigate mechanisms of vision loss and test potential therapeutics. ⋯ Ocular blast injury in the DBA/2 J mouse recapitulates damage that is characteristic of open globe injuries with the advantage of a physically intact globe that prevents complications from infection. The injury was more severe in DBA/2 J mice than in C57Bl/6 J mice, which have an intact ocular immune privilege. Early injury to the outer retina mostly recovers over time. In contrast, inner retinal dysfunction seems to drive later vision loss.
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Several lines of evidence suggest that CCL2 could initiate the hyperalgesia of neuropathic pain by causing central sensitization of spinal dorsal horn neurons and facilitating nociceptive transmission in the spinal dorsal horn. The cellular and molecular mechanisms by which CCL2 enhances spinal pain transmission and causes hyperalgesia remain unknown. The substantia gelatinosa (lamina II) of the spinal dorsal horn plays a critical role in nociceptive transmission. An activated spinal microglia, which is believed to release pro-inflammatory cytokines including TNF-α, plays an important role in the development of neuropathic pain, and CCL2 is a key mediator for spinal microglia activation. In the present study, we tested the hypothesis that spinal CCL2 causes the central sensitization of substantia gelatinosa neurons and enhances spinal nociceptive transmission by activating the spinal microglia and augmenting glutamatergic transmission in lamina II neurons. ⋯ In summary, our results suggest that an intrathecal injection of CCL2 causes thermal hyperalgesia by augmenting the excitatory glutamatergic transmission in substantia gelatinosa neurons through a presynaptic mechanism and facilitating nociceptive transmission in the spinal dorsal horn. Further studies show that intrathecal co-administration of minocycline, a specific inhibitor of microglial activation, or WP9QY, a selective TNF-α antagonist, completely inhibited CCL2 potentiation of glutamatergic transmission in substantia gelatinosa neurons and CCL2-induced heat hyperalgesia. The results of the present study suggest that peripheral nerve injury-induced upregulation of the spinal CCL2 level causes the central sensitization of substantia gelatinosa neurons by activating spinal microglia and that TNF-α mediates CCL2-induced thermal hyperalgesia and augmentation of glutamatergic transmission in lamina II neurons.