Cerebrospinal Fluid from Patients After Craniotomy with the Appearance of Interleukin-6 Storm Can Activate Microglia to Damage the Hypothalamic Neurons in Mice.

We monitored CSF (cerebrospinal fluid) for Th1/Th2 inflammatory cytokines in a patient with unexplained postoperative disturbance of consciousness after craniotomy and found that the level of IL-6 (interleukin-6) concentrations was extremely high, meeting the traditional criteria for an inflammatory cytokine storm. Subsequently, the cerebrospinal fluid specimens of several patients were tested, and it was found that IL-6 levels were increased in different degrees after craniotomy. Previous studies have focused more on mild and long-term IL-6 elevation, but less on the effects of this short-term IL-6 inflammatory cytokine storm. Cerebrospinal fluid rich in IL-6 may play a significant role in patients after craniotomy. The objective is to explore the degree of IL-6 elevation and the incidence of IL-6 inflammatory cytokine storm in patients after craniotomy, as well as the effect of IL-6 elevation on the brain. In this study, the levels and clinical manifestations of inflammatory factors in cerebrospinal fluid after craniotomy were statistically classified, and the underlying mechanisms were discussed preliminarily. CSF specimens of patients after craniotomy were collected, IL-6 level was measured at 1, 5, and 10 days after operation, and cognitive function was analyzed at 1, 10, and 180 days after surgery. Craniotomy mouse model, cerebrospinal fluid of patients with the appearance of IL-6 storm after craniotomy, and IL-6 at the same concentration stimulation model were established. Behavioral tests, fluorescence in situ hybridization (FISH), pathological means, western blot, and ELISA (enzyme-linked immune-sorbent assay) were performed for verification. CSF from patients after craniotomy caused disturbance of consciousness in mice, affected neuronal damage in the hypothalamus, activation of microglia in the hypothalamus, and decreased expression of barrier proteins in the hypothalamus and brain. The large amount of interleukin-6 in CSF after craniotomy was found to be mainly derived from astrocytes. The IL-6 level in CSF after craniotomy correlated inversely with patients' performance in MoCA test. High levels of IL-6 in the cerebrospinal fluid derived from astrocytes after craniotomy may lead to disruption of the brain-cerebrospinal fluid barrier, most notably around the hypothalamus, which might result in inflammatory activation of microglia to damage the hypothalamic neurons and impaired cognitive function/more gradual cognitive repairment in patients after craniotomy with the appearance of IL-6 storm.

Application of electromagnetic disturbance technology in predicting ventriculoperitoneal shunt dependency after aneurysm-associated subarachnoid hemorrhage.

BACKGROUND: The aim of this study was to evaluate the predictive power of electromagnetic disturbance technology in patients with hydrocephalus after subarachnoid hemorrhage. METHODS: This prospective, observational cohort study was conducted at The First Affiliated Hospital of Zhengzhou University and Nanfang Hospital. A total of 155 patients with subarachnoid hemorrhage (SAH) were enrolled in this study. Disturbance coefficients were recorded using a continuous sinusoidal signal in real time after SAH. The patients were divided into two groups: hydrocephalus group (patients who underwent shunt insertion within a month after SAH) and non-hydrocephalus group (patients without need for a ventriculoperitoneal shunt). We used SPSS to draw a ROC Curve to assess the ability of disturbance coefficients to predict the probability of hydrocephalus. RESULTS: Hydrocephalus occurred in 37 patients after SAH. The average disturbance coefficient of patients with hydrocephalus decreased by 25.14±9.78, and the disturbance coefficient of patients with no hydrocephalus decreased by 6.58±10.10 (one aspect of the present invention is a system of non-invasively monitoring hydrocephalus, cerebral edema, and intracranial bleeding comprising of a source emitting electromagnetic waves to brain tissue, a detector detecting said wave that propagates through said tissue, a signal conditioning unit amplifying and filtering said wave, a quadrature detector estimating magnitude and phases of said wave, and a parameter estimator calculating the complex wave number, relative attenuation coefficient (RAC), relative phase shift (RPS), wave speed change (WSC), and travel-time difference (TTD) of said brain, and assessing status of hydrocephalus and cerebral edema). The difference was statistically significant (t=9.825, P<0.001). The decrease in disturbance coefficient can be used to predict the occurrence of hydrocephalus, and if the disturbance coefficient decreases by more than 15.5 (sensitivity, 92.37%; specificity, 86.49%), it can be used to indicate the occurrence of hydrocephalus. CONCLUSIONS: The disturbance coefficient can predict the occurrence of hydrocephalus. The greater decline of the disturbance coefficient, the greater probability of occurrence of intracranial hydrocephalus. Hydrocephalus can be early detected. However, the CT scan is necessary to confirm the occurrence of hydrocephalus. Early diagnosis and early treatment may improve the prognosis of patients with hydrocephalus after subarachnoid hemorrhage.

Identification of Novel Cerebrospinal Fluid Biomarkers for Cognitive Decline in Aneurysmal Subarachnoid Hemorrhage: A Proteomic Approach.

Background: Cognitive impairment commonly occurs in aneurysmal subarachnoid hemorrhage (aSAH) survivors. Cerebrospinal fluid (CSF) biomarkers have been proven useful in several central neurological disorders. No such diagnostic biomarkers are available for predicting cognitive impairment after aSAH to date. Here, we aimed to identify novel CSF biomarkers for cognitive deficits after aSAH using an in-depth proteomic approach. Methods: We applied mass spectrometry with data independent acquisition (DIA) quantification to identify biomarker candidates in CSF samples from a well-characterized cohort comprising patients with impaired cognition (n = 9) and patients with intact cognition (n = 9). The potential biological processes and signaling pathways associated with differential proteins were analyzed using R software. The candidates were further validated in a larger independent cohort (n = 40) using ELISA. The diagnostic utility of these proteins was investigated by using receiver operating characteristic curve analysis. Results: In total, we identified 628 proteins. The discovery cohort revealed that 115 proteins were differentially expressed in cognitive impairment patients compared to patients with intact cognition (P < 0.05). Independent cohort replication confirmed NCAM2, NPTXR, NRXN2, RELN, and CNTN2 as sensitive and specific candidate biomarkers for disorders of cognition. Lower CSF levels of all biomarker candidates, except RELN, were associated with more pronounced cognitive decline. Conclusion: We identified and validated five CSF biomarkers for cognitive impairment in aSAH patients. These particular proteins have important predictive and discriminative potential for cognitive impairment in aSAH and could be potential targets for early disease intervention.

Activation of Age-Related Nuclear Factor-κB Signaling Pathway Leads to Chronic Inflammation and Pituitary Fibrosis.

OBJECTIVE: The purpose of the present study was to investigate the mechanism of pituitary fibrosis in elderly people. METHODS: First, 20 pituitary glands obtained from 11 elderly people and 9 young people were studied using Masson's trichrome staining for fibrosis detection. Second, pituitary glands from 12 male rats, including 6 aged rats (OM group) and 6 young rats (YM group), were also studied. Western blotting was performed to detect collagen 1 and phosphorylation of the nuclear factor (NF)-κB subunit p65 in the OM and YM groups. The levels of 8 proinflammatory cytokines (interleukin [IL]-1α, IL-1ß, IL-2, IL-4, IL-6, IL-8, interferon-γ, and tumor necrosis factor-α) in the rat pituitary glands were detected using liquid suspension chip technology. Enzyme-linked immunosorbent assays were performed to detect the growth hormone (GH) levels in the venous blood samples from the rats. Next, 12 aged rats were randomly divided into 2 groups: the QNZ (Q)+OM and normal physiological saline (N)+OM groups. The Q+OM and N+OM groups had undergone intervention by intraperitoneally injection of QNZ and physiological saline (1 mg/kg) for 28 days, respectively. Finally, biochemical and histological examinations were performed, including Masson's trichrome staining for fibrosis, Western blotting for phosphorylation of p65, Millipore multiplex bead arrays (Millipore, Billerica, Massachusetts, USA) for proinflammatory cytokine levels, and enzyme-linked immunosorbent assays for GH secretion. RESULTS: Fibrosis was detected in the elderly patient group. Collagen 1, phosphorylation of the NF-κB signaling pathway, and the proinflammatory cytokine levels showed a significant increase in the OM group. Compared with the N+OM group, pituitary fibrosis was alleviated in the Q+OM group, with an increase in GH secretion and decreased proinflammatory cytokine levels and NF-κB. CONCLUSIONS: Pituitary fibrosis was found in the elderly group, and the pathological change was antagonized by decreasing the proinflammatory cytokine levels using QNZ and further increasing GH secretion.

Incidence and Possible Predictors of Sodium Disturbance After Craniopharyngioma Resection Based on QST Classification.

OBJECTIVE: Serum sodium abnormalities are one of the most common manifestations after radical craniopharyngioma (CP) excision. The aim of this study was to report the incidence and possible predictors of serum sodium disturbance and explore features of sodium destabilization manifestation among QST classification results after CP resection. METHODS: A retrospective analysis was performed of clinical, biochemical, radiologic, and operative data for 134 successive patients who underwent primary CP removal between September 2016 and March 2018. Univariate and multivariate analyses were conducted to determine predictors. RESULTS: Sixty patients (44.8%) experienced hyponatremia and 67 patients (50%) hypernatremia; the median time of onset was 6 days and the first day after surgery, respectively. The incidence, onset, severity, and type of sodium disturbance among different types of CP differed significantly based on statistical tests (P < 0.05). Sodium disturbance was more common and severe in patients with type T tumors (P < 0.05). Age, tumor type, and preoperative diabetes insipidus were independent prognostic factors for obvious disorders of serum sodium. CONCLUSIONS: Hyponatremia/hypernatremia is common after primary CP resection. The site of tumor origin has a direct effect on the growth pattern of CP, which may serve as a useful index for anticipating sodium perturbation after surgery. The level of sodium in children and patients with type T tumors, preoperative diabetes insipidus should be monitored closely throughout hospitalization.