BackgroundCentral pain (CP) is a common clinical problem in patients with spinal cord injury (SCI). Recent studies found the pathogenesis of CP was related to the remodeling of the brain. We investigate the roles of iron overload and subsequent oxidative stress in the remodeling of the brain after SCI.MethodsWe established a rat model of central pain after SCI. Rats were divided randomly into four groups: SCI, sham operation, SCI plus deferoxamine (DFX) intervention, and SCI plus nitric oxide synthase (NOS) inhibitor treatment. Pain behavior was observed and thermal pain threshold was measured regularly, and brain levels of iron, transferrin receptor 1 (TfR1), ferritin (Fn), and lactoferrin (Lf), were detected in the different groups 12 weeks after establishment of the model.ResultsRats demonstrated self-biting behavior after SCI. Furthermore, the latent period of thermal pain was reduced and iron levels in the hind limb sensory area, hippocampus, and thalamus increased after SCI. Iron-regulatory protein (IRP) 1 levels increased in the hind limb sensory area, while Fn levels decreased. TfR1 mRNA levels were also increased and oxidative stress was activated. Oxidative stress could be inhibited by ferric iron chelators and NOS inhibitors.ConclusionsSCI may cause intracranial iron overload through the NOS–iron-responsive element/IRP pathway, resulting in central pain mediated by the oxidative stress response. Iron chelators and oxidative stress inhibitors can effectively relieve SCI-associated central pain.

BackgroundCentral pain (CP) is a common clinical problem in patients with spinal cord injury (SCI). Recent studies found the pathogenesis of CP was related to the remodeling of the brain. We investigate the roles of iron overload and subsequent microglia activate in the remodeling of the brain after SCI.MethodsAn SCI-induced CP model was established in Sprague-Dawley rats that were randomly assigned to SCI, sham operation, deferoxamine (DFX), minocycline, and nitric oxide synthase inhibitor treatment groups. At 12 weeks, pain behavior and thermal pain threshold were evaluated in each group, and iron transferrin receptor (TfR)1 and ferritin (Fn) mRNA, as well as iron-regulatory protein (IRP)1, FN, lactoferrin, and nuclear factor (NF)-κB protein levels in the rat brains were measured. Microglia proliferation and differentiation and IRP1 expression were evaluated by immunohistochemistry.ResultsAutophagy was observed in rats after SCI, accompanied by reduced latency of thermal pain, increased iron content and IRP1 and NF-κB levels in the hindlimb sensory area, hippocampus, and thalamus, and decreased Fn levels in the hindlimb sensory area. TfR1 mRNA expression was upregulated in activated microglia. Treatment with an iron-chelating agent, or inhibitors of nitric oxide synthase or microglia suppressed microglia proliferation.ConclusionsSCI may induce intracranial iron overload, which activates microglia via NF-κB signaling. Microglia secrete inflammatory factors that induce neuronal damage and lead to CP. Treatment with an iron-chelating agent or NF-κB or microglia inhibitors can relieve CP resulting from SCI.

Although many studies have focused on the effects of elevated atmospheric CO 2 on algal growth, few of them have demonstrated how CO 2 interacts with carbon absorption capacity to determine the algal competition at the population level. We conducted a pairwise competition experiment of Phormidium sp., Scenedesmus quadricauda, Chlorella vulgaris and Synedra ulna. The results showed that when the CO 2 concentration increased from 400 to 760 ppm, the competitiveness of S. quadricauda increased, the competitiveness of Phormidium sp. and C. vulgaris decreased, and the competitiveness of S. ulna was always the lowest. We constructed a model to explore whether interspecific differences in affinity and flux rate for CO 2 and HCO 3 − could explain changes in competitiveness between algae species along the gradient of atmospheric CO 2 concentration. Affinity and flux rates are the capture capacity and transport capacity of substrate respectively, and are inversely proportional to each other. The simulation results showed that, when the atmospheric CO 2 concentration was low, species with high affinity for both CO 2 and HCO 3 − (HCHH) had the highest competitiveness, followed by the species with high affinity for CO 2 and low affinity for HCO 3 − (HCLH), the species with low affinity for CO 2 and high affinity for HCO 3 − (LCHH) and the species with low affinity for both CO 2 and HCO 3 − (LCLH); when the CO 2 concentration was high, the species were ranked according to the competitive ability: LCHH > LCLH > HCHH > HCLH. Thus, low resource concentration is beneficial to the growth and reproduction of algae with high affinity. With the increase in atmospheric CO 2 concentration, the competitive advantage changed from HCHH species to LCHH species. These results indicate the important species types contributing to water bloom under the background of increasing global atmospheric CO 2 , highlighting the importance of carbon absorption characteristics in understanding, predicting and regulating population dynamics and community composition of algae.