Comparison of the performance of two depression rating scales in patients with epilepsy in southern China.

OBJECTIVE: The aim of this study was to evaluate and compare the performance of the Chinese version of the Neurological Disorder Depression Inventory for Epilepsy (CNDDI-E) with that of the depression subscale of the Hospital Anxiety and Depression Scale (C-HADS-D) as screening tools for depression in the same patients with epilepsy (PWE). METHODS: A total of 213 consecutive PWE were evaluated. Receiver operating characteristic (ROC) analysis was performed using the C-NDDI-E and C-HADS-D as predictors and the Chinese version of the Mini International Neuropsychiatric Interview (C-MINI) as the gold standard. RESULTS: The area under the curve (AUC) for the C-NDDI-E was 0.870, and the optimal cutoff score was >11 (sensitivity 85.71%, specificity 79.78%); for the C-HADS-D, the AUC was 0.804, and the optimal cutoff score was >5 (sensitivity 85.71%, specificity 62.36%). The AUC for the C-NDDI-E was larger than the AUC for the C-HADS-D, but the comparison of the AUCs revealed no significant differences (P = 0.1444). CONCLUSION: Our findings indicate that the C-NDDI-E and C-HADS-D have high validity and support the use of these screening tools for depression in PWE. Moreover, the C-NDDI-E is a better screening scale for diagnosing depression than the C-HADS-D according to the results of this study.

Striatal overexpression of ß-arrestin2 counteracts L-dopa-induced dyskinesia in 6-hydroxydopamine lesioned Parkinson's disease rats.

Prolonged administration of Levodopa (L-dopa) therapy can generate L-dopa-induced dyskinesia (LID). Accumulating evidence indicates that hyper-activation of the dopamine D1 receptor (D1R) and the cAMP signaling cascade in the medium spiny neurons (MSNs) of the striatum are involved in LID. Previous studies have shown that striatal ß-arrestin2 overexpression significantly reduces LID severity and have indicated that ß-arrestin2 may play a causal role in the dyskinesia sensitization process. L-dopa-induced changes in the expression of signaling molecules and other proteins in the striatum were examined immunohistochemically and by western blot. A rAAV (recombinant adeno-associated virus) vector was used to overexpress and ablate ß-arrestin2. We found that striatal overexpression of AAV-mediated ß-arrestin2 produced less severe AIMs (abnormal involuntary movements) in response to L-dopa, whereas selective deletion of ß-arrestin2 in the striatal neurons dramatically enhanced the severity of dyskinesia induced by L-dopa. Furthermore, no significant improvements in motor behavior (FFT: forelimb functional test) were seen with the inhibition or overexpression of ß-arrestin2. Finally, overexpression of ß-arrestin2 diminished L-dopa-induced D1R and phosphor-DARPP32/ERK levels. Viral deletion of ß-arrestin2 markedly enhanced the key biochemical markers in the direct pathway. We found that increased availability of ß-arrestin2 ameliorated dyskinesia severity with no influence on the anti-Parkinsonian action of L-dopa, suggesting a promising approach for controlling LID in Parkinson's disease. In addition, overexpression of ß-Arrestin2 prevented the development of LID by inhibiting G protein-dependent D1R and phosphor-DARPP32/ERK signaling in dyskinetic rats.

The adenosine A2A receptor antagonist SCH58261 reduces macrophage/microglia activation and protects against experimental autoimmune encephalomyelitis in mice.

Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease of the central nervous system (CNS) affecting more than 2.5 million individuals worldwide. In the present study, myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) mice were treated with adenosine receptor A2A antagonist SCH58261 at different periods of EAE development. The administration of SCH58261 at 11-28 days post-immunization (d.p.i.) with MOG improved the neurological deficits. This time window corresponds to the therapeutic time window for MS treatment. SCH58261 significantly reduced the CNS neuroinflammation including reduced local infiltration of inflammatory cells, demyelination, and the numbers of macrophage/microglia in the spinal cord. Importantly, SCH58261 ameliorated the EAE-induced neurobehavioral deficits. By contrast, the SCH58261 treatment was ineffective when administered at the beginning of the onset of EAE (i.e., 1-10 d.p.i). The identification of the effective therapeutic window of A2A receptor antagonist provide insight into the role of A2A receptor signaling in EAE, and support SCH58261 as a candidate for the treatment of MS in human.

Reliability and validity of the Chinese version of the Patient Health Questionnaire 9 (C-PHQ-9) in patients with epilepsy.

OBJECTIVE: The aim of this study was to evaluate the clinical reliability and validity of the Chinese version of the Patient Health Questionnaire 9 (C-PHQ-9) in patients with epilepsy. METHODS: A total of 213 consecutive adult patients with epilepsy were evaluated. Receiver operating characteristic (ROC) analysis was performed using C-PHQ-9 and Chinese version of Patient Health Questionnaire 2 (C-PHQ-2) as predictors and the Mini International Neuropsychiatric Interview Plus Version 5.0.0 as the gold standard. RESULTS: The C-PHQ-9 was easily understood and quickly finished by the patients. According to the gold standard, the prevalence of current major depressive disorder in this population was 16.4%. Cronbach's α coefficient for the C-PHQ-9 was 0.860. The ROC analysis showed an area under the curve (AUC) of 0.888 (95% confidence interval [CI] = 0.838-0.927). At a cutoff score of >6, the C-PHQ-9 had a sensitivity of 82.86%, a specificity of 84.27%, a positive predictive value of 50.9%, and a negative predictive value of 96.2%. The C-PHQ-2 at a cutoff score of >1 resulted in the greatest balance of sensitivity and specificity (77.14% and 75.28%, respectively). CONCLUSION: Our findings support a high reliability and validity for the C-PHQ-9 as a screening tool for the detection of current major depression in Chinese patients with epilepsy.

Analysis of risk factors for antiepileptic drug-induced adverse psychotropic effects in Chinese outpatients with epilepsy.

Antiepileptic drugs (AEDs) have adverse psychotropic effects (APEs). To explore the risk factors for AED-induced APEs, we compared Chinese outpatients with epilepsy with and without AED-induced APEs. We reviewed the medical data of outpatients with epilepsy enrolled in the Epilepsy Long-term Follow Up Registry Study (ELFURS) between January 1, 2003 and December 31, 2015. Data on demographics, comorbidities, variables related to epilepsy, AED use, and APEs were collected. APEs were determined by experienced epileptologists based on the definition of "adverse drug reaction (ADR)" proposed by the World Health Organization (WHO) in 1972, and the causality relationship between APEs and suspected medications was assessed based on the WHO-UMC scale. APEs included effects on memory, sleep, behavior, mood, psychotic symptoms, and others in this study. We divided the study population into patients with and without AED-induced APEs and then compared the differences between the two groups using univariate and multivariate methods. A total of 3074 eligible patients were included in this study (1001 patients with AED-induced APEs and 2073 patients without AED-induced APEs). Of all APEs, the effects on memory and sleep were most pronounced. The results show that the female sex (odds ratio [OR] 1.242, 95% confidence interval [CI] 1.055-1.463), psychotic disorder comorbidities (OR 1.815, 95% CI 1.159-2.841), polytherapy with AEDs (OR 1.400, 95% CI 1.061-1.847), and the duration of epilepsy (OR 1.010, 95% CI 1.000-1.020) are significant nondrug risk factors for AED-induced APEs. Recognizing risk factors for APEs may help determine optimal treatment strategies for epilepsy.

ß-arrestin2 alleviates L-dopa-induced dyskinesia via lower D1R activity in Parkinson's rats.

The cause of the L-dopa-induced dyskinesia (LID) has been ascribed to G-protein coupled receptor (GPCR) supersensitivity and uncontrolled downstream signaling. It is now supposed that ß-arrestin2 affects GPCR signaling through its ability to scaffold various intracellular molecules. We used the rAAV (recombinant adeno-associated virus) vectors to overexpress and ablation of ß-arrestin2. L-dopa-induced changes in expression of signaling molecules and other proteins in the striatum were examined by western blot and immunohistochemically. Our data demonstrated that via AAV-mediated overexpression of ß-arrestin2 attenuated LID performance in 6-OHDA-lesioned rodent models. ß-arrestin2 suppressed LID behavior without compromising the antiparkinsonian effects of L-dopa. Moreover, we also found that the anti-dyskinetic effect of ß-arrestin2 was reversed by SKF38393, a D1R agonist. On the contrary, the rat knockdown study demonstrated that reduced availability of ß-arrestin2 deteriorated LID performance, which was counteracted by SCH23390, a D1R antagonist. These data not only demonstrate a central role for ß-arrestin2/GPCR signaling in LID, but also show the D1R signal pathway changes occurring in response to dopaminergic denervation and pulsatile administration of L-dopa.

Effects of mGluR5 Antagonists on Parkinson's Patients With L-Dopa-Induced Dyskinesia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Modulation of Metabotropic glutamate receptor 5 (mGluR5) may be a novel therapeutic approach to manage Parkinson's disease (PD) Patients with L-dopa-induced dyskinesia (LID). Objectives: The objective of this meta-analysis was to evaluate the effects of mGluR5 antagonists for the treatment of LID patients. Methods: Several electronic databases were consulted up to July 30, 2017. Randomized clinical trials (RCTs) that compared mGluR5 antagonists vs. placebo in LID patients were included. Pooled weighted mean difference (WMD) with 95% confidence intervals (CIs) were calculated using random-effects models. Results: Nine trials including 776 patients met all inclusion criteria. We pooled the whole data and found apparent difference between mGluR5 antagonists and placebo in terms of mAIMS (p = 0.010). However, there was no significant improvements on antidyskinetic in terms of LFADLDS (p = 0.42) and UPDRS Part IV (p = 0.20). Meanwhile, the effect size of UPDRS part III was similar in mGluR5 antagonist groups with in placebo groups (p = 0.25). Adverse events incidence was higher with mGluR5 antagonists than with placebo, especially at the expense of increased dizziness (16.3 vs. 4.3%), visual hallucination (10.1 vs. 1.1%), or fatigue (10.1 vs. 4.8%). Conclusions: mGluR5 antagonists had a greater treatment effect on the mAIMS in LID patients, however, there was no improvements on antidyskinetic in terms of LFADLDS and UPDRS Part IV compared with placebo. According to these results, we unable to recommend mGluR5 antagonists for the routine treatment of LID patients right now.

Modulation of CaMKIIa-GluN2B interaction in levodopa-induced dyskinesia in 6-OHDA-lesioned Parkinson's rats.

Long-term treatment with L-dopa leads to involuntary aimless movements called L-dopa-induced dyskinesia (LID) has hindered its use in Parkinson's disease (PD) patients. Emerging evidence suggests a possible role of CaMKIIa and its interacting partners in the development of LID. In this study, we found that CaMKIIa was found to form complexes with GluN2B after chronic administration of L-dopa in adult rat striatal neurons. Intrastriatal injection of KN-93 significantly reduced the level of GluN2B in CaMKIIa precipitates with a dose dependent response, as well as reduced the Global ALO AIM score without ablation of the therapeutic response to L-dopa. In parallel, intrastriatal injection of MK-801 significantly alleviated the level of CaMKIIa in GluN2B precipitates compared to LID group (p < 0.01), and this is accompanied by realizing improvement of the Global ALO AIM score also without affect the efficacy of L-dopa. In summary, the present study indicated that CaMKIIa-GluN2B interaction had an important role in the development of LID. Disrupt of this link by intrastriatal infusion of KN-93 or MK-801 ameliorated dyskinesia in 6-OHDA-lesioned PD rats.

An Overview of Meta-Analyses of Endovascular Bridging Therapies for Acute Ischemic Stroke.

BACKGROUND: Acute Ischemic Stroke (AIS) is a common cause of death worldwide and the leading cause of long-term severe disability. Endovascular bridging therapies (EBT), including endovascular thrombectomy (ET) and intra-arterial thrombolytic (IAT), have been recommended to realize a favorable functional outcome for AIS patients. METHODS: An overview of meta-analyses of primary randomized controlled trial (RCT) studies was performed evaluating EBT for AIS patients compared with usual care. RESULTS: Ten meta-analyses were included in this overview. ET was associated with a higher incidence of achieving functional outcome improvement, defined as a modified Rankin scale of 0 to 1 (mRS, p = 0.003), 0 to 2 (p < 0.00001), and 0 to 3 (p = 0.005). The risk of symptomatic intracranial hemorrhage (sICH) rate and all-cause mortality were similar between the two groups. Moreover, IAT treatment was also related to significantly improved outcomes in terms of the mRS score (p < 0.05), but no significant difference in rates of sICH and mortality within 90 days. CONCLUSIONS: In conclusion, our analysis supports that EBT, regardless of format (e.g., ET or IAT), is superior to the best medical therapy alone (e.g., IVT) in terms of mRS score in patients with AIS. In addition, the safety of EBT is similar to IVT.

Garcin syndrome caused by parotid gland adenoid cystic carcinoma: A case report.

RATIONALE: Garcin syndrome is characterized by the gradual involvement, and ultimately, unilateral paralysis of at least 7 and sometimes all cranial nerves, without intracranial hypertension or any long tract signs. PATIENT CONCERNS: We report the case of a 59-year-old woman who presented with Garcin syndrome, which gradually progressed over a period of 2 years. DIAGNOSIS: A left parotid gland biopsy revealed parotid gland adenoid cystic carcinoma (PGACC) with perineural invasion of a peripheral nerve bundle and lymph node metastasis. INTERVENTIONS: The patient was treated 3 times with local-field palliative radiotherapy. OUTCOMES: She died after several months. LESSONS: To the best of our knowledge, this is the first report of PGACC presenting as Garcin syndrome. PGACC is a rare tumor with a high propensity for perineural spread, and it should be considered as a possible cause of Garcin syndrome.

A Meta-Analysis of Folic Acid in Combination with Anti-Hypertension Drugs in Patients with Hypertension and Hyperhomocysteinemia.

Folic acid is generally used to lower homocysteine concentrations and prevent stroke and cardiovascular disease (CVD) at present. However, the efficacy of therapies that lower homocysteine concentrations in reducing the risk of CVD and stroke remains controversial. Our objective was to do a meta-analysis of relevant randomized controlled trials (RCTs) to evaluate the efficacy of folic acid supplementation among patients with hypertension and Hyperhomocysteinemia (HT/HHcy). We included RCTs examining the effects of folic acid plus antihypertensive therapy compared to antihypertensive alone. Weighted Mean Difference (WMD) and Relative risk (RR) were used as a measure of the effect of folic acid on the outcome measures with a random effect model. Sixty-five studies including 7887 patients met all inclusion criteria. Among them, 49 trials reported significant effect of combination therapy for reducing SBP (systolic Blood Pressure) and DBP (Diastolic Blood Pressure) levels compared with antihypertensive alone (WMD = -7.85, WMD = -6.77, respectively). Meanwhile, folic acid supplementation apparently reduced the level of total homocysteine (WMD = 5.5). In addition, folic acid supplementation obviously reduced the risk of cardiovascular and cerebrovascular events (CVCE) by 12.9% compared with control groups. In terms of the stratified analyses, a bigger beneficial effect was seen in those RCTs with treatment duration of more than 12 weeks, a decrease in the concentration of total homocysteine of more than 25%, with folic acid fortification. Our findings indicated that folic acid supplementation was effective in the primary prevention of CVCE among HT/HHcy patients, as well as reducing the blood pressure and total homocysteine levels.

Neuroprotective properties of curcumin in toxin-base animal models of Parkinson's disease: a systematic experiment literatures review.

BACKGROUND: Curcumin (diferuloylmethane), a polyphenol extracted from the plant Curcuma longa, is widely used in Southeast Asia, China and India in food preparation and for medicinal purposes. Meanwhile, the neuroprotective actions of curcumin have been documented for experimental therapy in Parkinson's disease (PD). METHODS: In this study, we used a systematic review to comprehensively assess the efficacy of curcumin in experimental PD. Using electronic and manual search for the literatures, we identified studies describing the efficacy of curcumin in animal models of PD. RESULTS: We identified 13 studies with a total of 298 animals describing the efficacy of curcumin in animal models of PD. The methodological quality of all preclinical trials is ranged from 2 to 5. The majority of the experiment studies demonstrated that curcumin was more significantly neuroprotection effective than control groups for treating PD. Among them, five studies indicated that curcumin had an anti-inflammatory effect in the PD animal models (p < 0.05). Meanwhile, four studies showed the antioxidant capability of curcumin, by which it protected substantia nigra neurons and improved striatal dopamine levels. Furthermore, two studies in this review displayed that curcumin treatment was also effective in reducing neuronal apoptosis and improving functional outcome in animal models of PD. Most of the preclinical studies demonstrated the positive findings while one study reported that curcumin had no beneficial effects against Mn-induced disruption of hippocampal metal and neurotransmitter homeostasis. CONCLUSIONS: The results demonstrated a marked efficacy of curcumin in experimental model of PD, suggesting curcumin probably a candidate neuroprotective drug for human PD patients.

ß-Ga2O3:Cr(3+) nanoparticle: A new platform with near infrared photoluminescence for drug targeting delivery and bio-imaging simultaneously.

Multifunctional nanoparticles which integrate the therapeutic agents and bio-imaging agents into one carrier are emerging as a promising therapeutic platform. Herein, GaOOH:Cr(3+) was firstly synthesized using improved hydrothermal method (atmospheric pressure, 95 °C), and by manipulating the pH of the reaction medium, GaOOH:Cr(3+) with different sizes (125.70 nm, 200.60 nm and 313.90 nm) were synthesized. Then ß-Ga2O3:Cr(3+) nanoparticles with porous structures were developed as a result of the calcination of GaOOH:Cr(3+). The fabricated, porous ß-Ga2O3:Cr(3+) nanoparticles could effectively absorb doxorubicin hydrochloride (DOX) (loading rate: 8% approximately) and had near infrared photoluminescence with a 695 nm emission. Furthermore, ß-Ga2O3:Cr(3+) nanoparticles were coated with l-Cys modified hyaluronic acid (HA-Cys) by exploiting the electrostatic interaction and the cross-link effect of disulfide bond to improve the stability. The DOX loaded HA-Cys coated ß-Ga2O3:Cr(3+) nanoparticles (HA/ß-Ga2O3:Cr(3+)/DOX) showed an oxidation-reduction sensitive drug release behavior. The HA-Cys coated ß-Ga2O3:Cr(3+) nanoparticles showed a low cytotoxicity on MCF-7 and Hela cell lines. The cellular uptake of HA/ß-Ga2O3:Cr(3+)/DOX using the near infrared photoluminescence of ß-Ga2O3:Cr(3+) nanoparticles and the fluorescence of DOX demonstrated the HA/ß-Ga2O3:Cr(3+)/DOX could internalize into tumor cells quickly, which was affected by the size and shape of ß-Ga2O3:Cr(3+)nanoparticles.

Brain protection conferred by long-term administration of 2-(2-benzofuranyl)-2-imidazoline against experimental autoimmune encephalomyelitis.

Our previous studies showed that 2-(2-benzofuranyl)-2-imidazoline (2-BFI), a ligand to type 2 imidazoline receptor, was protective against brain and spinal cord injury caused by experimental autoimmune encephalomyelitis (EAE). In the present study, we investigated the effect of long-term administration of 2-BFI and the dose-dependent response relationship of long-term administration of 2-BFI with neuroprotection. Treatment with 2-BFI at doses of 5, 10, and 20 mg/kg for 14 days significantly reduced hind limb paralysis and the severity of EAE compared with the EAE control group. Long-term use of 2-BFI was not only safe to mice, but also dose-dependently reduced the expression of inflammatory cytokines, including TNF-α, Interferon-γ and Interleukin-17A, compared with the EAE control group. Expressions of neuronal injury markers, including cytochrome c, AIF and ß-APP, were also reduced significantly in response to long-term 2-BFI treatment. Together, these results provided new evidence to demonstrate that 2-BFI is a safe and effective candidate for further development as a therapeutic drug for treatment of multiple sclerosis.

Idazoxan reduces blood-brain barrier damage during experimental autoimmune encephalomyelitis in mouse.

We have previously shown that Idazoxan (IDA), an imidazoline 2 receptor ligand, is neuroprotective against spinal cord injury caused by experimental autoimmune encephalomyelitis (EAE) in mouse, an animal modal of multiple sclerosis (MS). However, the protective mechanism remains unclear. Here, we provided evidence to show that IDA confers neuroprotection through reduction in blood-brain barrier (BBB) damage. EAE was induced by immunizing C57 BL/6 mice with myelin oligodendrocyte glycoprotein35-55 amino acid peptide (MOG35-55). IDA was administrated for 14 days after MOG immunization at 2 mg/kg (i.p., bid). Significant reduction in BBB damage occurred in the IDA-treated group of mice compared with the saline-treated group, as evidenced by the reduction in Evan׳s blue content in the brain tissue and the reduced BBB tight junction damage viewed under a transmission electron microscope. Moreover, EAE-induced reductions in tight junction proteins (JAM-1, Occludin, Claudin-5 and ZO-1) were also significantly ameliorated in IDA-treated mice, all of which supported the notion that IDA reduced BBB damage. Interestingly, the expression levels of extracellular matrix metalloproteinase-9 (MMP-9) and the ratio of MMP-9 against tissue inhibitor of metalloproteinase-1 (TIMP-1), which is known to be associated with MS-induced BBB damage, were significantly reduced in IDA-treated group, lending further support to the hypothesis that IDA confers brain protection through reducing BBB damage. This study raised a possibility that IDA is a promising pro-drug for development against MS.

[Progress in the study of core-crosslinked polymeric micelles in drug delivery system].

The core-crosslinked polymeric micelles were used as a new drug delivery system, which can decrease the premature drug release in blood circulation, improve the stability of the micelles, and effectively transport the drug into the therapy sites. Then the drug bioavailability increased further, while the side effect reduced. Most drugs were physically entrapped or chemically covalent with the polymer in the internals of micelles. Based on the various constitutions and properties of polymeric micelles as well as the special characteristics of body microenvironment, the environment-responsive or active targeting core-crosslinked micelles were designed and prepared. As a result, the drug controlled release behavior was obtained. In the present paper, the research progress of all kinds of core-crosslinked micelles which were published in recent years is introduced. Moreover, the characteristic and application prospect of these micelles in drug delivery system are analyzed and summarized.

Chronic caffeine treatment attenuates experimental autoimmune encephalomyelitis induced by guinea pig spinal cord homogenates in Wistar rats.

Dysfunction of adenosinergic systems has been implicated in the development of multiple sclerosis in humans and experimental autoimmune encephalomyelitis (EAE) in animals. Caffeine, a non-selective antagonist of adenosine receptors, has been shown to provide protection against myelin oligodendroglia glycoprotein (MOG)-induced EAE in mice. In this study, we showed that chronic caffeine similarly imparts neuroprotection against EAE induced in rats by guinea pig spinal cord homogenates (GPSCH). GPSCH-induced EAE is characterized by extensive tissue inflammation with a typical chronic disease course. We showed that caffeine decreases the incidence of EAE and attenuates EAE pathology at behavioral, histological (inflammatory cell infiltration and demyelination) and neurochemical (expression of inflammatory cytokines) levels. The attenuation of GPSCH-induced pathology by chronic caffeine treatment was observed at doses of 10 and 30 mg/kg and during both peak and recovery phases of EAE. Furthermore, it was showed that chronic treatment with caffeine up-regulated A1 receptor and TGF-beta mRNAs and suppressed interferon-gamma mRNA in EAE rats. Together with previous reports, our data demonstrates that chronic treatment with caffeine exerts a neuroprotective effect against EAE, possibly through an A(1) receptor-mediated shift from Th1 to Th2 cell function, and provides a neurobiological basis for epidemiological investigation into the possible relationship between caffeine consumption and development of multiple sclerosis in humans.

Idazoxan attenuates spinal cord injury by enhanced astrocytic activation and reduced microglial activation in rat experimental autoimmune encephalomyelitis.

Idazoxan, an imidazoline 2 receptor (I(2)R) ligand, has been shown to protect against brain injury in several animal models of neurological disorders. In the present study we investigated the effect of idazoxan on experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. EAE was induced by immunizing Wistar rats with guinea pig spinal cord homogenates emulsified in CFA, followed by daily treatment of idazoxan (0, 0.5 mg/kg, 1.5 mg/kg, 4.5 mg/kg, i.p, bid) for 10 days. The results showed that the treatment of idazoxan (1.5 mg/kg and 4.5 mg/kg) significantly decreased the incidence and alleviated inflammatory cell infiltration and demyelination in spinal cords and cerebral cortex. Furthermore, the protective effect of idazoxan on EAE was associated with the enhanced astrocytic activation and attenuated microglial activation and with the subsequent down-regulated expression of proinflammatory cytokines IL-12p40 and IFN-gamma and up-regulated expression of anti-inflammatory cytokines IL-10 and TGF-beta(1). Thus, the daily treatment of the I(2)R ligand idazoxan for 10 days attenuates EAE pathology by differential modulation of astrocytic and microglial activations, raising a possibility that the I(2)R ligand may be a novel strategy for treating EAE.