Objective To investigate the effect of hemoglobin on structure and function of blood-brain barrier (BBB) in rat models after intracerebral hemorrhage.Methods One hundred and eight male SD rats were randomized into normal control group (n=12),intracerebral hemoglobin injection group (Hb group,n=48) and sham-operated group (n=48); according to the different observation time points,rats in the Hb group and sham-operated group were divided into 4 subgroups (6 and 24 h,3 and 7 d after the injection,n=1 2).Histological changes and iron deposition of the brain tissues were examined with HE staining and iron staining,respectively.BBB permeability was evaluated by the permeation of Evens blue.The expressions of claudin-5 and ZO-1 in perihematomal brain tissues were detected by immunofluorescence staining and real-time fluorescence quantitative PCR.Results Evident edema and necrosis were observed in the perihematomal zone of Hb group,and iron deposition was found 3 and 7 days after the injection.The permeation of Evens blue in Hb group was significantly increased as compared with that in sham-operated group (P＜0.05).Immunofluorescence staining indicated that expressions ofclaudin-5 and ZO-1 were low and discontinuous in Hb group; the mRNA expression levels of claudin-5 and ZO-1 in Hb group were significantly lower than those in the sham-operated group (P＜0.05).Conclusion After intracerebral hemorrhage,Hb may induce the damage of BBB and participate in the course of brain edema.
Key words:
Hemoglobin; Blood-brain barrier; Tight junction; Brain edema
This study aimed to discuss the pathogenesis, clinical manifestation, diagnosis, and treatment of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis.The diagnosis and treatment of 2 cases with teratoma-associated anti-NMDAR encephalitis were summarized and the clinical data of patients reported by domestic and international studies were reviewed in this study. The 2 cases were both adolescent females who showed mental abnormalities as their main clinical manifestation. The patients were positive for anti-NMDAR antibody in their serum and cerebrospinal fluid, and gynecologic ultrasound detected ovarian teratoma. After diagnosis, the patients underwent teratoma resection, followed by pulse therapy of hormones and gamma globulin. Chemotherapy was performed to prevent tumor recurrence, and patients were in a stable condition.Teratoma-associated anti-NMDAR encephalitis is commonly seen in young women. The clinical manifestation of this disease is nonspecific, and the patients mainly have fever, psychosis, and seizure. Tumor resection and immune therapy are effective treatment strategies, and standardized chemotherapy should also be performed to prevent recurrence.
Cognitive impairment in Parkinson's disease (PD) involves the cholinergic system and cholinergic neurons, especially the nucleus basalis of Meynert (NBM/Ch4) located in the basal forebrain (BF). We analyzed associations between NBM/Ch4 volume and cortical thickness to determine whether the NBM/Ch4-innervated neocortex shows parallel atrophy with the NBM/Ch4 as disease progresses in PD patients with cognitive impairment (PD-MCI).We enrolled 35 PD-MCI patients, 48 PD patients with normal cognition (PD-NC), and 33 age- and education-matched healthy controls (HCs), with all participants undergoing neuropsychological assessment and structural magnetic resonance imaging (MRI). Correlation analyses between NBM/Ch4 volume and cortical thickness and correlation coefficient comparisons were conducted within and across groups.In the PD-MCI group, NBM/Ch4 volume was positively correlated with cortical thickness in the bilateral posterior cingulate, parietal, and frontal and left insular regions. Based on correlation coefficient comparisons, the atrophy of NBM/Ch4 was more correlated with the cortical thickness of right posterior cingulate and precuneus, anterior cingulate and medial orbitofrontal lobe in PD-MCI versus HC, and the right medial orbitofrontal lobe and anterior cingulate in PD-NC versus HC. Further partial correlations between cortical thickness and NBM/Ch4 volume were significant in the right medial orbitofrontal (PD-NC: r=0.3, P=0.045; PD-MCI: r=0.51, P=0.003) and anterior cingulate (PD-NC: r=0.41, P=0.006; PD-MCI: r=0.43, P=0.013) in the PD groups and in the right precuneus (r=0.37, P=0.04) and posterior cingulate (r=0.46, P=0.008) in the PD-MCI group.The stronger correlation between NBM/Ch4 and cortical thinning in PD-MCI patients suggests that NBM/Ch4 volume loss may play an important role in PD cognitive impairment.
The efficacy and safety of Tai-Kang-Ning (TKN) capsule, a traditional Chinese medicine formula, for the treatment of acute heroin withdrawal syndrome were investigated by conducting a double-blind, double-dummy, positive-controlled, and randomized trial. Sixty-four patients with acute heroin withdrawal syndrome were recruited. These patients were treated with either TKN or lofexidine in a fixed schedule of doses for 10 days. The results indicate that both treatments significantly reduced withdrawal symptoms by day 3, but there was no significant difference overall between lofexidine and TKN in efficacy or safety. These results demonstrate that TKN is effective in the treatment of moderate-to-severe acute heroin withdrawal syndrome with mild adverse effects.
Intracerebral hemorrhage (ICH) is a severe cerebrovascular disease with high morbidity and mortality rates. Oxidative stress and inflammation are important pathological mechanisms of secondary brain injury (SBI) after ICH. Brain and muscle Arnt-like protein 1 (BMAL1), which forms the core component of the circadian clock, was previously shown to be involved in many diseases and to participate in oxidative stress and inflammatory responses. However, the role of BMAL1 in SBI following ICH is unknown. In addition, treatments targeting miR-155 and its downstream signaling pathway may exert a beneficial effect on SBI after ICH, while miR-155 may regulate Bmal1 mRNA stability and translation. Nevertheless, researchers have not clearly determined whetheantagomir-155 upregulates BMAL1 expression and subsequently attenuates ICH-induced brain injury in rats.After establishing an ICH rat model by injecting autologous blood, the time course of changes in levels of the BMAL1 protein after ICH was analyzed. Subsequently, this study was designed to investigate the potential role and mechanisms of BMAL1 in SBI following ICH using lentiviral overexpression and antagomir-155 treatments.BMAL1 protein levels were significantly decreased in the ICH group compared to the sham group. Genetic overexpression of BMAL1 alleviated oxidative stress, inflammation, brain edema, blood-brain barrier injury, neuronal death, and neurological dysfunction induced by ICH. On the other hand, we observed that inhibiting miRNA-155 using antagomir-155 promoted the expression of BMAL1 and further activated the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway to attenuate brain injury after ICH.These results reveal that BMAL1 serves as a neuroprotective agent in ICH and upregulation of BMAL1 attenuates ICH-induced SBI. Therefore, BMAL1 may be a promising therapeutic target for SBI following ICH.
Diabetic patients are known to have an independent risk of cardiomyopathy. Hyperglycemia leads to upregulation of reactive oxygen species (ROS) and inflammatory condition that may contribute to diabetic cardiomyopathy. There are evidences that the activation of AMPK is playing pivotal role in the lipid and glucose metabolism. 2,3,5,4’-Tetrahydroxystilbene-2-O-β-D-glucoside (TSG) from Polygoni multiflori has been demonstrated to possess a variety of pharmacological activities, including antioxidant, anti-inflammatory and anti-atherosclerotic effect. The present study was sought to investigate the effect of TSG on modulating diabetic cardiomyopathy and the mechanisms involved.
Methods
A high-fat diet and low-dose streptozotocin administration were used to induce type 2 diabetes in Wistar rats. Diabetic rats were treated with TSG for 16 weeks. At the end of this study, after cardiac function measurements were performed, rats were sacrificed and their hearts were harvested for further histologic and molecular biologic analysis. Cardiac tissue was analysed by ELISA for the protein content of the cytokines TNF-alpha, IL-6, IL-1beta, and TGF-beta. Phosphorylation of AMP was analysed by western blot, and the total cardiac collagen content was analysed by Sirius red staining.
Results
Results showed that the levels of nitric oxide (NO) and superoxide dismutase (SOD) activity in plasma and myocardium in TSG-treated group were significantly higher than those in diabetic control group. The levels of malondialdehyde (MDA) in plasma and myocardium in TSG-treated group were significantly lower than those in diabetic control group. Hyperglycemia markedly enhanced cardiac production of proinflammatory cytokine IL-1 beta. TSG reduced IL-1 beta but increased TNF-alpha and IL-6 levels in the diabetic cardiomyopathy. The AMPK protein phosphorylation and expression levels were remarkably reduced in diabetic cardiac tissues. In contrast, TSG treatment significantly rescued the AMPK protein expression and phosphorylation compared to non-treated diabetic group
Conclusions
These findings indicate that the protective mechanisms of TSG on diabetic cardiomyopathy are involved in the alleviation of oxidative stress injury and regulating proinflammatory cytokines, partially via activation of AMPK protein.
Acknowledgements
This work was supported by the National Nature Science Foundation of China (NSFC) Grant 81000576 to Fei Cai, Natural Science Foundation of Hubei Province of China 2011CDB315 to Shou-yi Gan.
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