Optical coherence tomography in patients with Wilson's disease.

BACKGROUND: Morphological changes of retina in patients with Wilson's disease (WD) can be found by optical coherence tomography (OCT), and such changes had significant differences between neurological forms (NWD) and hepatic forms (HWD) of WD. The aim of this study was to evaluate the relationship between morphological parameters of retina and brain magnetic resonance imaging (MRI) lesions, course of disease, type of disease, and sexuality in WD. METHODS: A total of 46 WD patients and 40 health controls (HC) were recruited in this study. A total of 42 WD patients were divided into different groups according to clinical manifestations, course of disease, sexuality, and brain MRI lesions. We employed the Global Assessment Scale to assess neurological severity of WD patients. All WD patients and HC underwent retinal OCT to assess the thickness of inner limiting membrane (ILM) layer to retinal pigment epithelium layer and inner retina layer (ILM to inner plexiform layer, ILM-IPL). RESULTS: Compared to HWD, NWD had thinner superior parafovea zone (108.07 ± 6.89 vs. 114.40 ± 5.54 µm, p < .01), temporal parafovea zone (97.17 ± 6.65 vs. 103.60 ± 4.53 µm, p < .01), inferior parafovea zone (108.114 ± 7.65 vs. 114.93 ± 5.84 µm, p < .01), and nasal parafovea zone (105.53 ± 8.01 vs. 112.10 ± 5.44 µm, p < .01) in inner retina layer. Course of disease influenced the retina thickness. Male patients had thinner inner retina layer compared to female patients. CONCLUSION: Our results demonstrated that WD had thinner inner retina layer compared to HC, and NWD had thinner inner retina layer compared to HWD. We speculated the thickness of inner retina layer may be a potential useful biomarker for NWD.

Elderly onset of MELAS in a male: A case report.

Background: Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) is one of the most common maternally inherited mitochondrial diseases which rarely affects elderly people. Case presentation: We reported the case of a 61-year-old male patient with MELAS. He was experiencing acute migraine-like headaches as the first symptoms. Laboratory data showed elevated lactate and creatine kinase levels. Brain magnetic resonance imaging (MRI) found a high signal intensity lesion in the left occipital-temporal-parietal lobe on diffusion-weighted imaging (DWI). Magnetic resonance angiography (MRA) revealed reversible vasoconstriction of the middle cerebral arteries and superficial temporal arteries. A muscle biopsy suggested minor muscle damage. A genetic study revealed a mitochondrial DNA A3243G mutation. Conclusion: Elderly onset of MELAS is rare and easily misdiagnosed as an ischemic stroke. MELAS with the onset of stroke-like episodes should be considered in adult or elderly patients with imaging findings that are atypical for cerebral infarction. The use of multimodal MRI in the clinical diagnosis of MELAS could be extremely beneficial.

Clinical features and power spectral entropy of electroencephalography in Wilson's disease with dystonia.

OBJECTIVE: To study the clinical features and power spectral entropy (PSE) of electroencephalography signals in Wilson's disease (WD) patients with dystonia. METHODS: Several scale evaluations were performed to assess the clinical features of WD patients. Demographic information and electroencephalography signals were obtained in all subjects. RESULTS: 34 WD patients with dystonia were recruited in the case group and 24 patients without dystonia were recruited in the control group. 20 healthy individuals were included in the healthy control group. The mean body mass index (BMI) in the case group was significantly lower than that in the controls (p < .05). The case group had significantly higher SAS, SDS, and Bucco-Facial-Apraxia Assessment scores (p < .05). Total BADS scores in the case group were lower than those in the control group (p < .01). Note that 94.11% of the case group presented with dysarthria and 70.59% of them suffered from dysphagia. Dysphagia was mainly related to the oral preparatory stage and oral stage. Mean power spectral entropy (PSE) values in the case group were significantly different (p < .05) from those in the control group and the healthy group across the different tasks. CONCLUSIONS: The patients with dystonia were usually accompanied with low BMI, anxiety, depression, apraxia, executive dysfunction, dysarthria and dysphagia. The cortical activities of the WD patients with dystonia seemed to be more chaotic during the eyes-closed and reading tasks but lower during the swallowing stages than those in the control group.

A rare brainstem anaplastic astrocytoma.

Background: Anaplastic astrocytoma (AA) is rarely observed in the brainstem and the clinical symptoms and imaging manifestations vary, which present a great challenge to accurate clinical diagnosis. Case description: A 56-year-old woman, with a month-long history of nausea and vomiting, was first diagnosed with acute cerebral infarction and demyelinating disease. The patient showed negative results on enhanced magnetic resonance and 18F-fluorodeoxyglucose positron emission tomography-computed tomography, and the clinical symptoms were not typical, leading to early misdiagnosis. Conclusion: Finally, the patient was diagnosed with AA by pathological biopsy.

A patient with hereditary transthyretin amyloidosis involving multiple cranial nerves due to a rare p.(Phe84Ser) variant.

We report a 30-year-old man involving gastrointestinal symptoms, vitreous opacity, and multiple cranial neuropathies. Transthyretin-related hereditary amyloidosis genetic testing revealed a rare c.251T > C variant p.(Phe84Ser). Only four cases with this variant have been reported before.

Prognostic value of platelet/lymphocyte ratio and CAMI-STEMI score for major adverse cardiac events in patients with acute ST segment elevation myocardial infarction after percutaneous coronary intervention: A prospective observational study.

ABSTRACT: The aim of this study was to investigate the predictive value of the platelet-to-lymphocyte ratio (PLR) and the China Acute Myocardial Infarction registry-ST segment elevation myocardial infarction (CAMI-STEMI) score for major adverse cardiovascular events (MACE) in ST-segment elevation myocardial infarction (STEMI) patients undergoing percutaneous coronary intervention (PCI) within 6 months.We enrolled STEMI patients who received emergency PCI in the First Hospital of Lianyungang from January 2016 to December 2019. The clinical characteristics of the patients, the PLR, and the CAMI-STEMI score were recorded. The MACE included heart failure, nonfatal re-infarction, recurrent angina pain, re-hospitalization for cardiovascular-related illness, repeat PCI, coronary artery bypass grafting, and all-cause mortality. According to the incidence of MACE during the follow-up the patients were divided into the MACE group (96 cases, 24.8%) and the non-MACE group (291 cases, 75.2%).The PLR, 147.62 (121.13-205.20) in MACE group, was 111.19 (90.23-146.42) in the non-MACE group in comparison, the PLR was higher in MACE group than that in non-MACE group (P < .01). Multivariate regression analysis showed that PLR (odds ratio (OR) = 1.007, 95% confidence interval (CI) 1.002-1.012, P < .01) and CAMI-STEMI score (OR = 1.575, 95% CI: 1.311-1.892, P < .01) were independent predictors of MACE. Besides, I-BIL was also an independent predictor of MACE (OR = 1.007, 95% CI: 1.011-1.146, P = .021). Reciever-operating characteristic curve showed that the area under curve of PLR was 0.704 (95%CI 0.644-0.763, P < .001). The cutoff value was 112.6, the sensitivity and specificity were 84.4% and 51.9%, respectively.PLR and CAMI-STEMI scores were independent risk factors of MACE after PCI in STEMI patients.

Persistence with medical treatment for Wilson disease in China based on a single center's survey research.

BACKGROUND: Wilson's disease (WD) is one of the few hereditary diseases that can be successfully treated with medicines. We conduct this survey research to assess treatment persistence among patients with WD and try to identify what factors affect the treatment persistence. METHODS: We employed WeChat which is the most popular social software in China to carry out this anonymous questionnaire research. The questionnaire included medication adherence scale. We also collected available medical records related to demographic and clinical characteristics. All the patients were divided into group of persistence with drug treatment (PDT) and nonpersistence with drug treatment (n-PDT). RESULTS: We collected 242 qualified questionnaires. Only 66.5% of patients were PDT during the mean 12.6 years of follow-up. In PDT group, better outcomes were observed: improvement (78.3%) and no change (16.1%) versus those in n-PDT (55.6%; and 28.4%, respectively). In PDT group, only nine patients deteriorated (6.8%) in comparison with 13 patients in n-PDT (16.0%). The adverse events (AEs) in PDT group were significantly less than those in n-PDT group. There were no significant differences in clinical type, gender, age, education level, and family knowledge about WD between the two groups. There were significant differences in AEs and family position toward treatment. CONCLUSION: Medication Adherence of Chinese WD patients was low. One third of the patients (33.5%) were unable to PDT, and it had an important negative effect on clinical outcome. AEs and family support had an important impact on treatment persistence.

MicroRNA-488-3p Regulates Neuronal Cell Death in Cerebral Ischemic Stroke Through Vacuolar Protein Sorting 4B (VPS4B).

BACKGROUND: Ischemic stroke, which often occurs with high morbidity, disability, and mortality, is a main cause of brain disease. In various types of human diseases, it is found that microRNAs (miRNAs) are considered as gene regulators. Increasing studies have proved that fluctuation of miRNAs, in the pathologies of ischemic stroke, plays a vital role. However, the accurate regulatory mechanism of cerebral ischemic stroke by miRNAs is still unclear. In this research, we investigated the inhibition mechanism of miR-488-3p on neuronal death through targeting vacuolar protein sorting 4B (VPS4B) in cerebral ischemia/reperfusion (I/R) injury. METHODS: Western blot and qRT-PCR were utilized to detect the miR-488-3p level and VPS4B expression. The cell counting kit-8 (CCK-8) assay was utilized to measure the function of miR-488-3p in cell death induced by oxygen glucose deprivation/reoxygenation (OGD/R). After middle cerebral artery occlusion/reperfusion (MCAO/R), the impact of miR-488-3p on infarct volume in mouse brain was assessed. The targets of miR-488-3p were confirmed by luciferase analysis and bioinformatics software. RESULTS: The miR-488-3p level remarkably reduced in primary neuronal cells administrated with OGD/R. Similarly, it also decreased in the mouse brain administrated with MCAO/R. Additionally, the up-regulation of miR-488-3p expression suppressed the death of neuronal cells and restrained ischemic brain infarction in ischemia-stroked mice. Besides, the results showed that VPS4B, which could be inhibited by miR-488-3p, was a direct target of miR-488-3p. This research revealed that the inhibition of VPS4B protected the neuronal cells in ischemic stroke both in vitro as well as in vivo. Meanwhile, this inhibition strengthened positive impact generated by miR-488-3p on ischemic injury. CONCLUSION: Overall, miR-488-3p played a critical role on neuroprotective function via reducing VPS4B protein level. These results performed a new underlying curative target for the treatment of cerebral ischemic stroke.

DIM mitigates the development of experimental autoimmune encephalomyelitis by maintaining the stability and suppressive function of regulatory T cells.

Recent studies have revealed that indoles, dietary ligands of the aryl hydrocarbon receptor (AhR), have immunomodulatory characteristics of balancing the differentiation of regulatory T cells (Tregs) and Th17 cells in multiple autoimmune diseases. In this study, we aimed to investigate the potency of the indole, 3,3'-diindolylmethane (DIM), on the stability and suppressive function of Tregs in experimental autoimmune encephalomyelitis (EAE). Furthermore, we used the AhR antagonist CH223191 to verify that DIM exerts its effects on Tregs through the activation of AhR. We found that DIM treatment significantly alleviated the severity of EAE by maintaining the stability and suppressive function of Tregs instead of facilitating the differentiation of Tregs. Thus, these DIM-treated Tregs might indirectly inhibit the generation of Th17 cells and the production of proinflammatory cytokines. And we confirmed the critical role of AhR in the EAE model. Our study further investigated the mechanisms by which dietary indoles promote Treg activity in the EAE model. DIM may act as a novel therapeutic to restrain autoimmune inflammation in multiple sclerosis.

Giant "heart appearance-like sign" on MRI in bilateral ponto-medullary junction infraction: case report.

BACKGROUND: Bilateral medial medullary infarction (MMI) is uncommon and bilateral medial pons infarction (MPI) is even rarer. "Heart appearance" on magnetic resonance imaging (MRI) is a characteristic presentation of bilateral medial medullary infarction (MMI). CASE PRESENTATION: We present 67-year-old Chinese diabetic and hypertensive female patient affected with "heart appearance-like" infarction in bilateral ponto-medullary junction on MRI. Abnormal signal was observed in the bilateral ponto-medullary junction on T1, T2, fluid-attenuated inversion recovery and apparent diffusion coefficient (ADC). The whole brain digital subtraction angiography (DSA) showed the basilar artery and vertebral artery remained intact. Therefore, we speculated that the bilateral ponto-medullary junction infarction might be caused by the deep perforating branch of the basilar artery. CONCLUSIONS: As far as we know, the "heart appearance-like" infraction in bilateral ponto-medullary junction was not reported. Our case also suggests that bilateral ischemic infraction involvement of the medulla and pon is possible even in the context of an intact basilar artery.

Dural Arteriovenous Fistula Complicated with Cerebral Venous Sinus Thrombosis.

BACKGROUND: Cerebral venous sinus thrombosis (CVST) is always confused with dural arteriovenous fistula (DAVF) in clinical practice; however, both of them are very rare cerebral vascular diseases. In this report, we provide one case of DAVF combined with CVST. CASE DESCRIPTION: A 75-year-old woman complained of headache with nausea and vomiting for 4 days. Magnetic resonance venography revealed filling defect in the torcular, left transverse, and sigmoid sinus, which strongly suggested sinus thrombosis. The patient underwent anticoagulation treatment for 9 days. However, the manifestation was not alleviated, magnetic resonance imaging detected the lesion was enlarged, and the midline shifted to the left. Digital subtraction angiography examination detected that one fistula classified as Borden type IA was fed by the left superficial temporal artery and drained into the left transverse and sigmoid sinus. Endovascular embolization with ethylene vinyl alcohol was conducted. CONCLUSIONS: Follow-up at 6 months indicated that the patient recovered without any sequelae.

miR-200b inhibits CD133+ glioma cells by targeting the AKT pathway.

MicroRNA-200b (miR-200b) is a tumor suppressor in multiple tumor types, including gastric cancer, breast cancer, ovarian cancer and glioma. The biological significance of a known normal and cancer stem cell marker, CD133, remains elusive. The aim of the present study was to identify the function and mechinism of miR-200b in suppressing CD133+ glioma cells. CD133+ glioma cells were sorted by flow cytometry. The expression of miR-200b, Ki67, GAP43, GFAP and CD133 were tested by reverse transcription-quantitative polymerase chain reaction. The binding of miR-200b to prominin 1 (PROM1) was certificated by luciferase reporter assay. Cell proliferation was analyzed by bromodeoxyuridine staining. The protein level of CD133, p-AKT, AKT and Notch1 was detected by western blot analysis. Analysis of glioma samples revealed that CD133 expression is negatively associated with miR-200b. PROM1, which is the gene that codes CD133, was certified to be a target of miR-200b. miR-200b expression inhibited the stemness properties and division of the CD133+ glioma cells. Our results identified a miR-200b/CD133/PI3K/Akt signaling axis, exploring the fundamental role of miR-200b and CD133 in glioma stem cell behavior.

Role of sestrin2 in H2O2-induced PC12 apoptosis.

Sestrin2 is involved in different kind of cellular response to stress conditions. However, the function of Sestrin2 in oxidative stress related neurological diseases remains unknown. In this study, we tested whether Sestrin2 has a beneficial effect on PC12 cell apoptosis induced by H2O2. We found that H2O2 induces expression of Sestrin2 in PC12 cells in a time-dependent and dose-dependent manner. We also found that Knockdown of Sestrin2 using small RNA interference promotes cell apoptosis induced by H2O2. In addition, our results show that the c-Jun NH(2)-terminal kinase (JNK)/c-Jun pathway is activated by H2O2. Inhibiting the activity of the JNK pathway and JNK siRNA transfection abolishes the increase of Sestrin2 induced by H2O2. These findings suggest that the inductive effect of Sestrin2 is mediated by the JNK/c-Jun pathway. In this study, we investigated the role of Sestrin2 in oxidative stress-induced cell apoptosis using PC12 cells as the model, implying that stimulating expression of Sestrin2 might be considered as a neuroprotective target against H2O2-induced oxidative stress.

Icariin exerts estrogen-like activity in ameliorating EAE via mediating estrogen receptor ß, modulating HPA function and glucocorticoid receptor expression.

BACKGROUND: Estrogen exerts neuroprotective and anti-inflammatory effects in EAE and multiple sclerosis (MS), but its clinical application is hindered due to side effects and risk of tumor. Phytoestrogen structurally or functionally mimics estrogen with fewer side effects than endogenous estrogen. Icariin (ICA), an active component of Epimedium extracts, demonstrates estrogen-like neuroprotective effects. However, it is unclear whether ICA is effective in EAE and what are the underlying mechanisms. OBJECTIVE: To determine the therapeutic effects of ICA in EAE and explore the possible mechanisms. METHODS: C57BL/6 EAE mice were treated with Diethylstilbestrol, different dose of ICA and mid-dose ICA combined with ICI 182780. The clinical scores and serum Interleukin-17 (IL-17), Corticosterone (CORT) concentrations were then analyzed. Western blot were performed to investigate the expressions of glucocorticoid receptor (GR), estrogen receptor alpha (ERα) and ERß in the cerebral white matter of EAE mice. RESULTS: High dose ICA is equally effective in ameliorating neurological signs of EAE as estrogen. Estrogen and ICA has no effects on serum concentrations of IL-17 in EAE. While the CORT levels were decreased by ICA at mid or high doses, the expressions of GR, ERα and ERß were up-regulated by estrogen or different doses of ICA in a dosedependent manner. Estrogen induced the elevation of ERα more markedly than ICA. In contrast, ICA at mid and high doses promoted ERß more significantly than estrogen. CONCLUSION: ICA exerts estrogen-like activity in ameliorating EAE via mediating ERß, modulating HPA function and up-regulating the expression of GR in cerebral white matter. ICA may be a promising therapeutic option for MS.

Chasing tics in the human brain: development of open, scheduled and closed loop responsive approaches to deep brain stimulation for tourette syndrome.

Tourette syndrome is a childhood-onset disorder characterized by a combination of motor and vocal tics, often associated with psychiatric comorbidities including attention deficit and hyperactivity disorder and obsessive-compulsive disorder. Despite an onset early in life, half of patients may present symptoms in adulthood, with variable degrees of severity. In select cases, the syndrome may lead to significant physical and social impairment, and a worrisome risk for self injury. Evolving research has provided evidence supporting the idea that the pathophysiology of Tourette syndrome is directly related to a disrupted circuit involving the cortex and subcortical structures, including the basal ganglia, nucleus accumbens, and the amygdala. There has also been a notion that a dysfunctional group of neurons in the putamen contributes to an abnormal facilitation of competing motor responses in basal ganglia structures ultimately underpinning the generation of tics. Surgical therapies for Tourette syndrome have been reserved for a small group of patients not responding to behavioral and pharmacological therapies, and these therapies have been directed at modulating the underlying pathophysiology. Lesion therapy as well as deep brain stimulation has been observed to suppress tics in at least some of these cases. In this article, we will review the clinical aspects of Tourette syndrome, as well as the evolution of surgical approaches and we will discuss the evidence and clinical responses to deep brain stimulation in various brain targets. We will also discuss ongoing research and future directions as well as approaches for open, scheduled and closed loop feedback-driven electrical stimulation for the treatment of Tourette syndrome.

Icariin has synergistic effects with methylprednisolone to ameliorate EAE via modulating HPA function, promoting anti-inflammatory and anti-apoptotic effects.

BACKGROUND: High-dose methylprednisolone (MP) is a clinically recommended therapeutic regimen for Multiple Sclerosis (MS), whereas some dreadful complications induced by it remain inevitable. Studies implied that estrogens might play neuroprotective and anti-inflammatory roles in EAE and MS and promote glucocorticoid efficacy. Icariin (ICA), a primary active component of Epimedium extracts, also possesses neuroprotective and estrogen-like effects with less adverse complication than estrogen. However, rare study focuses ICA's effects on MS or EAE. OBJECTIVE: Our purpose is to determine whether ICA has synergistic effects with MP in treating EAE and explore the possible mechanisms. METHODS: C57BL/6 EAE mice were received different dose of ICA combined with MP and single MP treatment. Then, the clinical scores and serum Interleukin-17 (IL-17), Corticosterone (CORT), Adrenocorticotropic Hormone (ACTH) concentrations were analyzed. Western blot and Flow Cytometry were used to investigate the expression of glucocorticoid receptor (GR) and cell apoptosis. RESULTS: ICA has cooperative effects with MP in decreasing serum IL-17 and CORT concentrations, up-regulating the expression of GR in cerebral white matter and attenuating the cell apoptosis in spinal cord, especially high-dose ICA combined with MP. CONCLUSION: ICA has synergistic effects with MP to ameliorate EAE via modulating hypothalamic-pituitary-adrenal (HPA) function, promoting anti-inflammatory and anti-apoptotic effects. ICA could be considered as a promising therapeutic option for MS.

Identification and characterization of a novel splice-site mutation in the Wilson disease gene.

This study aimed to identify aberrant transcripts of the new splice-site mutation c.3244-2A>C in the Wilson disease (WD) gene (ATPase, Cu++ transporting, beta polypeptide, ATP7B) and discuss its genotype and clinical phenotype. DNA and RNA were extracted from peripheral blood lymphocytes, amplified by polymerase chain reaction (PCR) and nested reverse transcription PCR (RT-nested PCR) to characterize the aberrant transcripts. RT-nested PCR product sequencing comparison showed that c.3244-2A>C splice-site mutation caused aberrant transcripts and formatted a new splice acceptor. Patient carrying the splice-site mutation c.3244-2A>C presented early onset age, severe clinical manifestations, and poor prognosis. WD patients with the splice-site mutation show severe clinical manifestations, indicating that aberrant transcripts have important implications for WD phenotype.

Mutational characterization of ATP7B gene in 103 Wilson's disease patients from Southern China: identification of three novel mutations.

Wilson's disease (WD) is an autosomal recessive inheritance disorder of copper metabolism due to mutations in the ATP7B gene. The distribution of ATP7B gene mutations is diverse in different population. This study aimed to examine the genotypes of the ATP7B mutant alleles in WD patients from Southern China. Genomic DNA was extracted from 103 WD patients and 60 healthy patients. Mutations were screened and detected by DNA sequencing. A total of 51 different ATP7B mutations were identified in WD patients, including six homozygous, 51 compound heterozygous, and 39 single heterozygotes. Three mutations were found to be novel, including one missense mutation (c.2549C>T) and two frameshift mutations (c.3851_3876del and c.1057delC). The most frequent mutations are Arg778Leu (18.93%), Ile1148Thr (8.74%), and Pro992Leu (4.37%). Different from the published results of early studies, Ile1148Thr was found to be the second common mutation in our cohort. The highest mutation detection rate was on exon 8 (43.69%), followed by exon 16 (24.27%), and exon 12 (17.48%). The total mutation detection rate on exon 8, 12, and 16 was 85.44%. No ATP7B gene mutation was found in healthy patients. In conclusion, we identified three novel mutations and Ile1148Thr as another hotspot mutation in WD patients from Southern China. Most of the mutations can be detected by screening exon 8, 12, and 16. Our research has further enriched the mutation spectrum of the ATP7B gene in Chinese and may help to develop genetic screening strategies of WD.

Association of transforming growth factor-ß1 gene C-509T and T869C polymorphisms with atherosclerotic cerebral infarction in the Chinese: a case-control study.

BACKGROUND: Transforming growth factor-ß1 (TGF-ß1) is a multifunctional cytokine involved in inflammation and pathogenesis of atherosclerosis. There is scant information on the relation between variations within the TGF-ß1 gene polymorphisms and risks of ischemic cerebrovascular diseases. Therefore, this case-controlled study was carried out to investigate the possible association of the TGF-ß1 gene C-509T and T869C polymorphisms, and their combined genotypes with the risk of atherosclerotic cerebral infarction (CI) in the Chinese population. RESULTS: We recruited 164 CI patients and 167 healthy control subjects who were frequency-matched for age and gender. The frequencies of the -509TT genotype and T allele gene were significantly higher in the CI group (P = 0.007, P = 0.006). The frequencies of +869CC genotype and C allele were higher in the CI group (P = 0.002, P = 0.004). In the CI group, the individuals with -509TT genotype had a significantly higher level of plasma triglyceride (TG) (P = 0.017). +869CC genotype correlated significantly with higher level of plasma low density lipoprotein cholesterol (LDL-c) in the CI group (P = 0.015). With haplotype analysis, the frequency of the -509T/+869C combined genotype was significantly higher in the CI group than in controls (P < 0.001). CONCLUSIONS: Our study suggests that C-509T and T869C gene polymorphisms in TGF-ß1 may be a critical risk factor of genetic susceptibility to CI in the Chinese population.

Super-high-dose methylprednisolone does not improve efficacy or induce glucocorticoid resistance in experimental allergic encephalomyelitis.

OBJECTIVE: To investigate whether a super-high dose (SHD) of methylprednisolone (MP) improves its efficacy or induces glucocorticoid (GC) resistance, and to explore the potential mechanisms of GC resistance in experimental allergic encephalomyelitis (EAE). METHODS: The therapeutic effects of SHD and low-dose MP were evaluated in EAE by analyzing clinical scores, pathological changes and cytokine production. Immunohistochemistry and RT-PCR were used to investigate the expression of GC receptor (GR) isoforms and splicing factor SRp30c. RESULTS: Both MP doses had similar therapeutic effects. The ratio of GRα to GRß was positively correlated with clinical score changes. However, there was no difference in the GRα/GRß ratio between SHD and low-dose MP groups. SRp30c mRNA was correlated with GRß expression. CONCLUSION: This study indicates that the GRα/GRß ratio is associated with GC sensitivity, and SRp30c may play an important role in promoting alternative splicing of GR pre-mRNA to generate GRß in EAE rats. Compared with low-dose MP, SHD MP does not improve efficacy or induce GC resistance.