Hydrocephalus is a severe complication that can result from intracerebral hemorrhage, especially if this hemorrhage extends into the ventricles. Our previous study indicated that the NLRP3 inflammasome mediates cerebrospinal fluid hypersecretion in the choroid plexus epithelium. However, the pathogenesis of posthemorrhagic hydrocephalus remains unclear, and therapeutic strategies for prevention and treatment are lacking. In this study, an Nlrp3−/− rat model of intracerebral hemorrhage with ventricular extension and primary choroid plexus epithelial cell culture were used to investigate the potential effects of NLRP3-dependent lipid droplet formation and its role in the pathogenesis of posthemorrhagic hydrocephalus. The data indicated that NLRP3-mediated dysfunction of the blood–cerebrospinal fluid barrier (B-CSFB) accelerated neurological deficits and hydrocephalus, at least in part, through the formation of lipid droplets in the choroid plexus; these lipid droplets interacted with mitochondria and increased the release of mitochondrial reactive oxygen species that destroyed tight junctions in the choroid plexus after intracerebral hemorrhage with ventricular extension. This study broadens the current understanding of the relationship among NLRP3, lipid droplets and the B-CSFB and provides a new therapeutic target for the treatment of posthemorrhagic hydrocephalus. Strategies to protect the B-CSFB may be effective therapeutic approaches for posthemorrhagic hydrocephalus.
BackgroundThe prognosis of hypertensive intracerebral hemorrhage (HICH) is poor at high altitudes. The objective of this study was to explore whether hyperbaric oxygen (HBO) can improve the results of computed tomography perfusion (CTP) imaging and the neurological function of patients with HICH, and influence the hemoglobin concentration.MethodThe patients with HICH were treated with puncture and drainage. Twenty-one patients (51.22% of 41 patients in total) were treated with HBO after the operation, and the other patients received conventional treatment. CTP was performed twice, and all indices were measured. Scatter plots were used to determine the effect of hemoglobin concentration on CTP imaging. Receiver operating characteristic (ROC) curves were plotted to analyze the effects of hemoglobin concentration and hematoma volume on recovery results. The patients were followed up for 6 months.ResultsForty-one patients with HICH were treated with puncture and drainage. In total, 21 were treated with HBO after the operation, and 20 received conventional treatment as the control group. No significant differences in the CBV and CBF values of the two groups were noted before treatment. After 10 days, the values of CBV and CBF in the HBO group were significantly higher than those in the control group. A scatter diagram showed there was no significant in the HBO group, but significant correlation for the CBV and CBF values in the control group’s hematoma center and margin. The ROC curves showed that hematoma volume had an influence on prognosis of the control group. The Glasgow Coma Scale (GOS) scores of the HBO group were significantly higher than those of the control group (p < 0.05).ConclusionsHBO therapy can improve the postoperative CBV and CBF values of patients with HICH and ameliorate their prognoses. There was no significant correlation between HBO group and hemoglobin concentration on admission.
Background: Neuroinflammation is a major detrimental role of secondary brain injury after spontaneously intracerebral hemorrhage (ICH). Neutrophil infiltration plays a key role in the pathophysiology of ICH, but the coming resource and mechanism is unknown. This study aims to investigate whether spleen-derived neutrophil infiltration accelerated neuroinflammation and the role of C1q classical pathway.Methods: Male C57 mice were subjected to collagenase-induced ICH. If necessary, splenectomy was performed 2 weeks prior to ICH induction or anti-C1q neutralizing antibody (50mg/kg) was injected intravenously into the tail vein 15 minutes prior. Immunohistochemistry, Propidium Iodide staining, western blotting, ELISA and qRT-PCR were used to study the change of molecular proteins, neuronal cells and inflammatory factors. 7.0T animal MRI was used to assess hydrocephalus.Results: At 0h, 6h, 12h, 24h and 48h post ICH induction, we found a significant increasing tendency of microglia activation and neutrophil infiltration around hematoma and that C1q upregulation was correlated with neuronal decrease, which peaked at 24h after ICH. Here, we demonstrated spleen atrophy and upregulation of neutrophil in spleen 24h after ICH. Splenectomy prior to ICH mice resulted in significant decrease of microglia and neutrophil infiltration compared with that in group of sham-splenectomy. Moreover, both anti-C1q antibody and splenectomy significantly attenuated neutrophil infiltration and neuron death, restored synapse VGAT, alleviated hydrocephalus and inflammatory factors, such as IL-1β, TNF-α and IL-6 after ICH.Conclusion: The study demonstrated that spleen is a major source of brain neutrophil infiltration after ICH. C1q-targeted inhibition of classic complement pathway could prevent spleen-derived neutrophil infiltration and attenuate ICH induced neuroinflammation, which provides a novel therapeutic approach for hemorrhagical stroke.
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