Predictive factors for delayed hyponatremia after transsphenoidal surgery in patients with pituitary adenomas.

Objective: The aim of this study was to evaluate the incidence and duration of delayed hyponatremia and to assess the factors influencing the development of delayed hyponatremia after transsphenoidal surgery (TSS) in pituitary adenomas. Methods: We retrospectively analyzed the clinical data of patients with pituitary adenoma who underwent TSS. Univariable and multivariable statistics were carried out to identify factors independently associated with the occurrence of delayed hyponatremia. Results: Of the 285 patients with pituitary adenoma who underwent microscopic TSS, 44 (15.4%) developed postoperative-delayed hyponatremia and 241 (84.6%) did not. The onset of delayed hyponatremia occurred an average of 5.84 days post-surgery and persisted for an average of 5.36 days. Logistic regression analysis showed the highest risk of delayed hyponatremia in patients with significant change in tumor cavity height (odds ratio (OR), 1.158; 95% CI, 1.062, 1.262; P = 0.001), preoperative hypothalamus-pituitary-thyroid axis hypofunction (OR, 3.112; 95% CI, 1.481, 6.539; P = 0.003), and significant difference in blood sodium levels before and 2 days after TSS (OR, 1.101; 95% CI, 1.005, 1.206; P = 0.039). Conclusions: Preoperative hypothyroidism, difference in blood sodium levels before and 2 days after TSS, and the change in tumor cavity height after TSS played important roles in predicting postoperative-delayed hyponatremia onset in patients with pituitary adenomas.

The Difference Between Preoperative and Postoperative Pituitary Stalk Deviation Angles Can Predict Delayed Hyponatremia After Transsphenoidal Surgery.

OBJECTIVE: Our aim was to assess the factors influencing the development of delayed hyponatremia after transsphenoidal surgery (TSS) for pituitary adenomas and analyze the effect of the difference between preoperative and postoperative pituitary stalk deviation angles on delayed hyponatremia. METHODS: A retrospective study was performed on the clinical data of patients with pituitary adenomas who were treated with TSS at a single institution. On the basis of the observation of indicators such as pituitary stalk deviation angle and length of "measurable pituitary stalk" on magnetic resonance imaging, we determined the predictors of postoperative delayed hyponatremia through univariate and multivariate analyses. RESULTS: Microscopic TSS was performed in 422 patients with pituitary adenoma, of whom 66 experienced postoperative delayed hyponatremia. Logistic regression analysis showed that the risk of delayed hyponatremia was greater for patients with a large difference between preoperative and postoperative pituitary stalk deviation angle (odds ratio = 1.040, 95% confidence interval: 1.018-1.051; P < 0.001) and a large difference in the "measurable pituitary stalk" (odds ratio = 1.128, 95% confidence interval: 1.011-1.258; P = 0.032), and patients with high blood sodium on the second day after surgery have a lower probability of developing delayed hyponatremia. CONCLUSIONS: This study is the first to suggest the important role of the difference between preoperative and postoperative pituitary stalk deviation angles in predicting the development of delayed hyponatremia after TSS for pituitary adenomas.

Skull hemophilia pseudotumor: A case report.

BACKGROUND: In this study, a rare case with hemophilia pseudotumor in the skull was reported. CASE PRESENTATION: The case was a 34-year-old male patient who was admitted to the hospital, with the complaint of dizziness for more than 1 month. The physical examination indicated that the patient was conscious, who could give right answers to the questions. Moreover, there was a bulge on the left frontal-temporal parietal bone. The head CT showed abnormal density lesions on the left frontal-temporal parietal bone, with multiple irregular calcifications within the border. Skull MRI showed a large clump-like mixed signal at the top of the left frontal ridge. After admission, the patient was subjected to complete preoperative preparation and surgical treatment. Neurological navigation was used to determine the extent of skull defect before surgery to make a surgical incision. Clotting factor VIII substitution therapy was used for the intraoperative and postoperative treatments. The lesion was completely removed. CONCLUSIONS: These results suggest that the skull hemophilia pseudotumor has been rarely seen. According to imaging examination, in combination with family history, the diagnosis can be confirmed. If there is no obvious occupying effect, conservative treatment can be tried. On the contrary, if there is an obvious occupying effect, surgical treatment might be effective, and coagulation factor VIII should be supplemented during the perioperative period.

Hemoglobin enhances miRNA-144 expression and autophagic activation mediated inflammation of microglia via mTOR pathway.

Intracerebral hemorrhage promotes autophagic activation of microglia and enhances neuroinflammation. MiRNAs are key factors to autophagy, contributed to negatively and posttranscriptionally regulate gene expression and function. However, the specific miRNAs involved in the intracerebral hemorrhage mediated microglia autophagic activation are unidentified. In this experiment, microglia was treated with hemoglobin. And then, miRNA-144 expression, autophagic activation and inflammation of microglia were detected. In addition, the mTOR target of miRNA-144 and its regulation were identified. Our data demonstrated that hemoglobin promoted miRNA-144 expression and autophagic activation mediated inflammation. Additionally, miRNA-144 targeted mTOR by directly interacting with the 3' untranslated regions (UTRs), mutations of the binding sites abolish the miRNA-144 responsiveness. Overexpression of mTOR decreased autophagic activation and inflammation of microglia. Therefore, our results suggested that miRNA-144 contributed to hemoglobin mediated autophagic activation and inflammation of microglia via mTOR pathway. And miRNA based treatment provided novel therapeutical strategy for intracerebral hemorrhage.

C5a/C5aR Pathway Plays a Vital Role in Brain Inflammatory Injury via Initiating Fgl-2 in Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) is a serious emergency with high mortality and morbidity. Up to date, a limited understanding of ICH pathogenesis is difficult to implement effective therapeutic strategy. Much evidence demonstrates that the complement cascade is activated after experimental ICH. However, the exact mechanism has not been well studied in ICH. In the current study, C57BL/6J mice were injected with autologous whole blood. C5a/C5aR levels, microglia infiltration, inflammatory cytokine, and fibrinogen-like protein 2 (Fgl-2) expression in the perihematomal region were analyzed following ICH. In addition, brain water content and neurological dysfunction were detected following ICH. Our data demonstrated that ICH induced complement activation, along with an increase of C5a/C5aR levels, microglia infiltration, and inflammatory cytokine levels. However, C5aR-/- mice exhibited significant attenuation of inflammatory reaction, accompanied by a remarkable reduction of Fgl-2, brain water content, and neurological dysfunction. Furthermore, inhibiting extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 efficiently inhibited C5a-mediated Fgl-2 production following ICH. Taken together, these data suggest that C5a/C5aR plays a vital role in the ICH-induced inflammatory damage via Fgl-2, and ERK1/2 and p38 pathways also are involved in the pathogenesis of ICH. Therefore, inhibition of C5a/C5aR activation might enlarge our insights in ICH therapy.

Programmed death (PD)-1 attenuates macrophage activation and brain inflammation via regulation of fibrinogen-like protein 2 (Fgl-2) after intracerebral hemorrhage in mice.

Neuroinflammation plays an important role in the recovery of brain injury in ICH. Macrophage is the major executor in the neuroinflammation and initiates neurological defects. Programmed death 1 (PD-1) delivers inhibitory signals that regulate the balance between T cell activation, tolerance, and immunopathology. PD-1 expression by macrophages plays a pathologic role in the innate inflammatory response. However, the exact role of PD-1 on inflammatory responses following ICH has not been well identified. In this experiment, PD-1 KO (PD-1 -/-) ICH mice and Wild-type (WT) ICH mice were caused by intracranial injection of type IV collagenase. The level of macrophage activation, inflammatory cytokines and fibrinogen-like protein 2 (Fgl-2) were detected using immunofluorescence staining and ELISA assays. In addition, brain edema and neurological scores of ICH mice were also measured. Our data demonstrated that ICH promoted PD-1 expression of macrophage and enhanced inflammatory cytokines and Fgl-2 concentrations. PD-1 -/- mice exhibited significantly higher expression of the inflammatory cytokines which initiate Fgl-2, than did their wild-type (WT) littermates. As a result, macrophage activation, cerebral edema and neurological deficit scores of PD-1 -/- mice were higher. In conclusion, our data demonstrate that PD-1 plays a vital role in brain inflammation via regulation of Fgl-2 after ICH, and that manipulation of PD-1 might be a promising therapeutical target in ICH.

Sinomenine inhibits microglia activation and attenuates brain injury in intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) causes morbidity and mortality and commonly follows the reperfusion after an ischemic event. Microglial activation mediated cytokine and protease secretion contributes to brain injury in ICH. Previous studies have shown that sinomenine possesses potent immunoregulatory properties. However, little is known about its exact role in ICH. In the present study, to investigate the effect of sinomenine on microglial cells inflammation, we treated ICH-challenged BV2 microglial cells with sinomenine in vitro, and explored its neuroprotection role in intracerebral hemorrhage in vivo. Changes in inflammatory cytokines, such as TNF-α, IL-1ß and IL-6, reactive oxygen species (ROS) and NF-κB activation NF-κB were observed. In addition, the neurological deficit and cerebral water content of ICH mice were studied. The results demonstrated that sinomenine could inhibit the release of these cytokines and attenuate ROS production in a dose-dependent manner, and reduce NF-κB activation. Furthermore, sinomenine markedly inhibited cerebral water content and neurological deficit. In conclusion, our findings suggest that sinomenine played the protective effects through inhibition of microglial inflammation, and the findings also provided a novel therapy to treat ICH induced brain injury.

Relationship between apolipoprotein E, D10S1225 polymorphisms and late-onset Alzheimer's disease.

BACKGROUND: There were some papers published in the Jonrnal of Science, December 2000 suggesting that one or more important susceptibility genes for late onset Alzheimer's disease (LOAD) were located on the long arm of chromosome 10. Linkage analysis showed maximum lod score close to D10S1225 loci, which indicated the loci might contribute to the etiology of Alzheimer's disease (AD). METHODS: Fifty-nine LOAD patients and 107 controls were recruited. Apolipoprotein E (ApoE) genotypes were determined by reverse dot blotting hybridization assay. The D10S1225 was genotyped by 12% nondenaturing polyacrylamide gels electrophoresis and analyzed by silver staining. Statistical analysis was used to compare genotype and allele distributions between LOAD group and control group for ApoE and D10S1225 polymorphisms. RESULTS: ApoE epsilon 4 was significantly higher in LOAD group in comparison with the control group (chi(2) = 6.530, P = 0.011). Seven different alleles of D10S1225 have been identified. The length of these gene fragments were 178 bp, 181 bp, 184 bp, 187 bp, 190 bp, 193 bp, and 196 bp, respectively. A total of 21 different genotypes were observed. There was no relationship between D10S1225 polymorphism and LOAD (chi(2) = 4.488, P > 0.05). Conclusion This study suggests that ApoE epsilon 4 is a risk factor for LOAD, however, the results indicated that there is not any possible linkage for disequilibria with a nearby AD risk gene near D10S1225.