Jing Ding

Interictal interleukin-17A levels are elevated and correlate with seizure severity of epilepsy patients.

Interleukin 17A (IL‐17A) is implicated in the pathogenesis of several neuroimmunologic diseases. We aimed to evaluate the relationship between IL‐17A and seizure severity in patients with epilepsy. Seventy patients with probable symptomatic epilepsy and 68 healthy controls were included. Interictal serum IL‐17A and related cytokine (IL‐23, IL‐6, IL‐1β, interferon gamma (IFN‐γ), and IL‐10) levels were measured. The relationship between seizure severity and cytokine concentrations was assessed by Spearman correlation and multivariate linear regression test. IL‐17A levels in the cerebrospinal fluid (CSF) were tested in 30 additional patients with epilepsy, either in the postictal or interictal period and 15 patients with idiopathic inflammatory demyelinating diseases (IIDDs). Interictal serum IL‐17A levels were significantly elevated in patients with epilepsy compared to controls. IL‐6, IFN‐γ, and IL‐1β levels were also markedly elevated. Spearman correlation analysis revealed positive correlation between IL‐17A, IL‐6 levels and Veterans Administration Seizures Frequency and Severity Rating Scale score(VA score); IFN‐γ, IL‐10 levels, and National Hospital Seizure Severity Scale (NHS3) score. In addition, IL‐17A levels correlated significantly with seizure frequency. Multivariate linear regression test showed that only IL‐17A levels were independently positively correlated with VA scores (B = 0.288, p = 0.027). Postictal IL‐17A levels in the CSF were significantly elevated compared to interictal patients and patients with IIDDs. Our results suggest that interictal IL‐17A levels correlated highly with seizure severity.

Acute phase homocysteine related to severity and outcome of atherothrombotic stroke

BACKGROUND Homocysteine (HCY) is associated with risk of stroke, but whether HCY affects stroke severity and prognosis remains controversial. We hypothesized HCY has an impact on atherothrombosis and this prospective study was aimed to explore the association between acute phase HCY with stroke severity and outcome in patients with atherothrombosis. METHODS Patients <72 h after symptom onset were categorized by the modified Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification and those typed as atherothrombosis were included. Neurologic function was assessed with National Institute of Health Stroke Score (NIHSS) <72 h after symptom onset and Modified Rankin Scale (mRS) and Barthel Index (BI) 6-month, 12-month and 18-month poststroke respectively. HCY was recorded <72 h after symptom onset. Participants were divided into hHCY (HCY>15 μmol/l) and nhHCY (HCY≤15 μmol/l). The correlation between HCY and mRS was analyzed. RESULTS 125 of 130 participants without HCY interventional therapy completed the 18-month follow-up. There was no difference in demographics, histories of hypertension, diabetes mellitus, coronary heart disease, previous cerebral vascular event, and plasma low-density lipoprotein between hHCY and nhHCY. NIHSS, mRS were significantly higher and BI was significantly lower in hHCY than in nhHCY. The 18-month recurrence rate in hHCY (21.0%) was significantly higher than that in nhHCY (6.8%). Spearman correlation analysis revealed correlation between HCY and mRS (p=0.000). By ordinal logistic regression, HCY was an independent predictor of 18-month mRS (odds ratio 1.08, 95% confidence interval 1.04-1.13, p=0.000). CONCLUSIONS Acute phase elevated HCY correlated with severity and prognosis in patients with atherothrombotic stroke.

Decreased Serum Hepcidin Concentration Correlates with Brain Iron Deposition in Patients with HBV-Related Cirrhosis

Purpose Excessive brain iron accumulation contributes to cognitive impairments in hepatitis B virus (HBV)-related cirrhotic patients. The underlying mechanism remains unclear. Hepcidin, a liver-produced, 25-aminoacid peptide, is the major regulator of systemic iron metabolism. Abnormal hepcidin level is a key factor in some body iron accumulation or deficiency disorders, especially in those associated with liver diseases. Our study was aimed to explore the relationship between brain iron content in patients with HBV-related cirrhosis and serum hepcidin level. Methods Seventy HBV-related cirrhotic patients and forty age- sex-matched healthy controls were enrolled. Brain iron content was quantified by susceptibility weighted phase imaging technique. Serum hepcidin as well as serum iron, serum transferrin, ferritin, soluble transferrin receptor, total iron binding capacity, and transferrin saturation were tested in thirty cirrhotic patients and nineteen healthy controls. Pearson correlation analysis was performed to investigate correlation between brain iron concentrations and serum hepcidin, or other iron parameters. Results Cirrhotic patients had increased brain iron accumulation compared to controls in the left red nuclear, the bilateral substantia nigra, the bilateral thalamus, the right caudate, and the right putamen. Cirrhotic patients had significantly decreased serum hepcidin concentration, as well as lower serum transferring level, lower total iron binding capacity and higher transferrin saturation, compared to controls. Serum hepcidin level negatively correlated with the iron content in the right caudate, while serum ferritin level positively correlated with the iron content in the bilateral putamen in cirrhotic patients. Conclusions Decreased serum hepcidin level correlated with excessive iron accumulation in the basal ganglia in HBV-related cirrhotic patients. Our results indicated that systemic iron overload underlined regional brain iron repletion. Serum hepcidin may be a clinical biomarker for brain iron deposition in cirrhotic patients, which may have therapeutic potential.

N-methyl-d-aspartate receptor NR2B subunit involved in depression-like behaviours in lithium chloride-pilocarpine chronic rat epilepsy model

Depression is a common comorbidity in patients with epilepsy with unclear mechanisms. This study is to explore the role of glutamate N-methyl-D-aspartate (NMDA) receptor NR1, NR2A and NR2B subunits in epilepsy-associated depression. Lithium chloride (Licl)-pilocarpine chronic rat epilepsy model was established and rats were divided into epilepsy with depression (EWD) and epilepsy without depression (EWND) subgroups based on forced swim test. Expression of NMDA receptor NR1, NR2A and NR2B subunits was measured by western blot and immunofluorescence methods. The immobility time (IMT) was significantly greater in Licl-pilocarpine model group than in Control group, which was also greater in EWD group than in EWND group. No differences of spontaneous recurrent seizure (SRS) counts over two weeks and latency were found between EWD and EWND groups. The number of NeuN positive cells was significantly less in Licl-pilocarpine model group than in Control group, but had no difference between EWD and EWND groups. The ratios of phosphorylated NR1 (p-NR1)/NR1 and p-NR2B/NR2B were significantly greater in the hippocampus in EWD group than in EWND group. Moreover, the expression of p-NR1 and p-NR2B in the CA1 subfield of hippocampus were both greater in Licl-pilocarpine model group than Control group. Selective blockage of NR2B subunit with ifenprodil could alleviate depression-like behaviours of Licl-pilocarpine rat epilepsy model. In conclusion, glutamate NMDA receptor NR2B subunit was involved in promoting depression-like behaviours in the Licl-pilocarpine chronic rat epilepsy model and might be a target for treating epilepsy-associated depression.

T2* MRI of minimal hepatic encephalopathy and cognitive correlates in vivo.

To evaluate regional brain iron deposition in minimal hepatic encephalopathy (MHE) patients using T2*‐weighted gradient‐echo imaging and to explore the relationship between T2* MR changes and cognitive performance.

Clinical risk factors for depressive symptoms in patients with epilepsy.

To investigate the relationships between demographic data, seizure‐related factors, anti‐epileptic drugs (AEDs) taking, and depressive symptoms in patients with epilepsy (PWE), determining the major clinical risk factors of depression.

Increased ratio of glutamate/glutamine to creatine in the right hippocampus contributes to depressive symptoms in patients with epilepsy

PURPOSE Our study aimed to investigate whether the glutamatergic system in the hippocampus is correlated with depressive symptoms in patients with epilepsy. METHODS Fifty patients with epilepsy were recruited and divided into three groups on the basis of their Hamilton Depression Rating Scale (HAMD) scores. Single-voxel proton magnetic resonance spectroscopy ((1)H-MRS) was carried out. Pearson correlation analysis and multiple linear regression analysis were performed to investigate any correlation between the variables of hippocampal metabolites and HAMD scores. RESULTS Proton magnetic resonance spectroscopy analysis showed that the ratio of glutamate/glutamine to creatine (Glx/Cr) in the right hippocampus was significantly increased in patients with moderate depression and correlated positively with HAMD scores. Multiple linear regression analysis showed that the ratio of Glx/Cr in the right hippocampus was an independent risk factor relating to depressive symptoms in patients with epilepsy. CONCLUSION A disturbance of the hippocampal glutamatergic system may be involved in the pathogenesis of depression in epilepsy.

Disease duration and arcuate fasciculus abnormalities correlate with psychoticism in patients with epilepsy

PURPOSE We sought to investigate the relationship between interictal personality changes and white matter abnormalities in epilepsy patients. METHODS A total of 65 individuals with epilepsy and 40 demographically matched controls were evaluated by Eysenck Personality Questionnaire (EPQ) and diffusion tensor imaging (DTI) on 3T. Fractional anisotropy (FA) values of fibers were acquired. The relationship between EPQ scores, clinical variables and FA values was confirmed by Pearson correlation analysis and multiple linear regression analysis. RESULTS Epilepsy patients had higher psychoticism scores (P score) and lower extraversion scores (E score) compared with controls. P scores were higher in patients with long duration (>10 years) and taking multiple antiepileptic drugs. No difference was found in E score according to all the clinical variables. Epilepsy patients showed significantly lower mean FA value compared with healthy controls in the bilateral uncinate fasciculus, cingulum bundle, arcuate fasciculus and forceps minor of the corpus callosum. Multivariate linear regression analysis revealed that duration of epilepsy and FA value of the right arcuate fasciculus was independent risk factors of psychoticism in epilepsy patients. CONCLUSIONS Long disease duration and impairment of arcuate fasciculus integrity may predispose the development of psychoticism in patients with epilepsy. Our results provide important insights into the pathophysiological mechanisms underlying personality change in epilepsy.

Functional network changes in the hippocampus contribute to depressive symptoms in epilepsy

PURPOSE Our study aimed to investigate the functional connectivity (FC) between the hippocampus and other brain regions in epilepsy patients with depressive symptoms. METHODS Epilepsy patients with and without depressive symptoms, assessed using the 17-item Hamilton Depression Rating Scale scores, were enrolled. Healthy volunteers were recruited as the control group. Resting state functional magnetic resonance imaging was performed, and the data were processed using Resting-State fMRI (DPARSFA2.0) software. The regional homogeneity (ReHo) values and the FC between the right hippocampus and other brain regions were analysed. RESULTS The ReHo value of the cerebellum (particularly the left cerebellar hemisphere) was significantly lower in epilepsy patients than in healthy controls, and was lower in epilepsy patients with depressive symptoms (EP + DS group) than in those without depressive symptoms (EP-DS group, p < 0.05). Additionally, the FC between the right hippocampus and the bilateral cerebellum was significantly greater in the EP + DS group than in the EP-DS group (p < 0.05). Moreover, abnormal ReHo values in the bilateral frontal lobes, including the right anterior cingulate cortex, and changes in the FC between the right hippocampus and the bilateral frontal lobes were found in the EP + DS group. Minor changes in the FC between the temporal and parietal lobes were also found in the epilepsy patients. CONCLUSION The functional right hippocampus-cerebellum circuit might contribute to the pathogenesis of depressive symptoms in epilepsy, with the exception of brain areas associated with emotion such as the frontal and temporal lobes. Modulating the hippocampus-cerebellum circuit is a potential therapeutic strategy for epilepsy patients with depressive symptoms.

Vascular Remodeling, Oxidative Stress, and Disrupted PPARγ Expression in Rats of Long-Term Hyperhomocysteinemia with Metabolic Disturbance

Hyperhomocysteinemia, a risk factor for vascular disease, is associated with metabolic syndrome. Our study was aimed at exploring the effect of long-term hyperhomocysteinemia with metabolic disturbances on vascular remodeling. We also studied oxidative stress and expression of PPARγ in the coronary arteriole as a possible mechanism underlying vascular remodeling. Rats were treated with standard rodent chow (Control) or diet enriched in methionine (Met) for 48 weeks. Plasma homocysteine, blood glucose, serum lipids, malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NO) levels were measured. Coronary arteriolar and carotid arterial remodeling was assessed by histomorphometric techniques and the expression of PPARγ in vessel wall was investigated. In Met group, an increase in the level of fasting blood glucose, serum triglyceride, total cholesterol, MDA, and NO, a decline in the serum SOD level, and increased collagen deposition in coronary and carotid arteries were found. Moreover, we detected decreased expression of PPARγ in the coronary arterioles in Met group. In summary, our study revealed metabolic disturbances in this model of long-term hyperhomocysteinemia together with vascular remodeling and suggested that impaired oxidative stress, endothelium dysfunction, and decreased PPARγ expression in the vessel wall could be underlying mechanisms.