Aiwu Zhang

Curcumin inhibits Aβ-induced microglial inflammatory responses in vitro: Involvement of ERK1/2 and p38 signaling pathways

Amyloid β (Aβ) plays an important role in Alzheimers disease (AD) by inducing microglia activation. Once activated, microglial cells promote the release of reactive species and cytokines that are known to enhance immune responses in AD brain. Thus, negative regulators of microglia activation are considered as potential therapeutic candidates for AD. Curcumin, the major yellow pigment in turmeric (Curcuma longa), is proposed for its anti-inflammatory properties. Several studies have indicated the suppressive effects of curcumin on LPS-induced microglia activation and MAPK activities. However, the effects of curcumin on Aβ-treated microglia and the possible mechanisms are still not fully understood. In the present study, we found that curcumin improved microglial viability against Aβ42 in a time- and dose-dependent manner and remarkably suppressed Aβ42-induced CD68 expression. Moreover, curcumin concentration-dependently abolished Aβ42-induced interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) production in mRNA and protein levels in microglia. Besides, curcumin exerted an inhibitory effect on phosphorylation of ERK1/2 and p38 in Aβ42-activated microglia. Further experiments indicated that blockage of ERK1/2 and p38 pathways reduced inflammatory cytokines production from microglia. These results show that curcumin suppresses ERK1/2 and p38 signaling, thus, attenuating inflammatory responses of brain microglia.

Effects of transcranial direct current stimulation on hemichannel pannexin-1 and neural plasticity in rat model of cerebral infarction.

The aim of this study was to investigate the effects of transcranial direct current stimulation (TDCS) on hemichannel pannexin-1 (PX1) in cortical neurons and neural plasticity, and explore the optimal time window of TDCS therapy after stroke. Adult male Sprague-Dawley rats (n=90) were randomly assigned to sham operation, middle cerebral artery occlusion (MCAO), and TDCS groups, and underwent sham operation, unilateral middle cerebral artery (MCA) electrocoagulation, and unilateral MCA electrocoagulation plus TDCS (daily anodal and cathodal 10 Hz, 0.1 mA TDCS for 30 min beginning day 1 after stroke), respectively. Motor function was assessed using the beam walking test (BWT), and density of dendritic spines (DS) and PX1 mRNA expression were compared among groups on days 3, 7, and 14 after stroke. Effects of PX1 blockage on DS in hippocampal neurons after hypoxia-ischemia were observed. TDCS significantly improved motor function on days 7 and 14 after stroke as indicated by reduced BWT scores compared with the MCAO group. The density of DS was decreased after stroke; the TDCS group had increased DS density compared with the MCAO group on days 3, 7, and 14 (all P<0.0001). Cerebral infarction induced increased PX1 mRNA expression on days 3, 7, and 14 (P<0.0001), and the peak PX1 mRNA expression was observed on day 7. TDCS did not decrease the up-regulated PX1 mRNA expression after stroke on day 3, but did reduce the increased post-stroke PX1 mRNA expression on days 7 and 14 (P<0.0001). TDCS increased the DS density after stroke, indicating that it may promote neural plasticity after stroke. TDCS intervention from day 7 to day 14 after stroke demonstrated motor function improvement and can down-regulate the elevated PX1 mRNA expression after stroke.

A Randomized, One‐Year Clinical Trial Comparing the Efficacy of Topiramate, Flunarizine, and a Combination of Flunarizine and Topiramate in Migraine Prophylaxis

OBJECTIVES The objective of this study was to observe the efficacy, safety, and side effects of a combination of flunarizine plus topiramate compared with either flunarizine and or toparamate alone for migraine prophylaxis. METHODS Out of 150 patients with migraine recruited into the study and randomly assigned to one of three conditions, 126 completed the trial in their group: flunarizine (39), topiramate (44), and flunarizine plus topiramate (43). Patient information was assessed at enrollment and at follow-up visits at the end of months 1-3, 6, 9, and 12. The primary measure of efficacy reduction in mean monthly migraine frequency of at least 50% as compared with baseline. Secondary efficacy parameters included reduction in mean monthly migraine days and severity of headache. Side effects were compared in the three groups by recording adverse reactions and weight changes. RESULTS The proportion whose monthly headache frequency decreased more than 50% was 66.7% (26/39) in the flunarizine group, 72.7% (32/44) in the topiramate group and 76.7% (33/43) in the combination group, respectively (P=0.593). The mean monthly days and severity of headache in the three groups also declined and was more significant in the flunarizine plus topiramate group than in the flunarizine group and the topiramate group (P<0.05). In the flunarizine group, the average weight change was 0.6kg. Topiramate was associated with a mean weight loss was of -0.9kg in the topiramate group and -0.2kg in the flunarizine plus topiramate group. CONCLUSION Flunarizine, topiramate, and the combination of flunarizine with topiramate are all effective and have good tolerability in migraine prophylaxis. Adding topiramate to flunarizine may reduce the latters impact on body weight.

Primary angiitis of the central nervous system: report of eight cases from Southern China

Background and purpose:  This study is to report the clinical, neuroimaging and pathological characteristics of patients with primary angiitis of the central nervous system (PACNS) from Southern China.

Telomerase: A Target for Therapeutic Effects of Curcumin and a Curcumin Derivative in Aβ1-42 Insult In Vitro

This study was designed to investigate whether telomerase was involved in the neuroprotective effect of curcumin and Cur1. Alzheimers disease is a consequence of an imbalance between the generation and clearance of amyloid-beta peptide in the brain. In this study, we used Aβ1-42 (10 µg/ml) to establish a damaged cell model, and curcumin and Cur1 were used in treatment groups. We measured cell survival and cell growth, intracellular oxidative stress and hTERT expression. After RNA interference, the effects of curcumin and Cur1 on cells were verified. Exposure to Aβ1–42 resulted in significant oxidative stress and cell toxicity, and the expression of hTERT was significantly decreased. Curcumin and Cur1 both protected SK-N-SH cells from Aβ1–42 and up-regulated the expression of hTERT. Furthermore, Cur1 demonstrated stronger protective effects than curcumin. However, when telomerase was inhibited by TERT siRNA, the neuroprotection by curcumin and Cur1 were ceased. Our study indicated that the neuroprotective effects of curcumin and Cur1 depend on telomerase, and thus telomerase may be a target for therapeutic effects of curcumin and Cur1.

Atorvastatin attenuates NF-κB activation in trigeminal nucleus caudalis in a rat model of migraine

Nitroglycerin-induced NF-kappaB activation in trigeminal nucleus caudalis is believed to be partly involved in the pathogenesis of migraine. Atorvastatin, an inhibitor of HMG-CoA reductase, is thought to have pleiotropic effects in various neurologic diseases. Moreover, there are several lines of evidences that atorvastatin inhibits NF-kappaB activation in peripheral blood mononuclear cells. Thus, this study aims to explore whether atorvastatin attenuates NF-kappaB activation in trigeminal nucleus caudalis in a nitroglycerin-induced migraine model. A significant increase in nuclear content of p65, an indicator of NF-kappaB activation, was detected in trigeminal nucleus caudalis in rats following injection with nitroglycerin. However, the nitroglycerin-induced NF-kappaB activation in trigeminal nucleus caudalis was attenuated by pretreatment with atorvastatin in a dose-dependent fashion. These results suggest that atorvastatin may be a novel and promising candidate for future treatment or prophylaxis of migraine via attenuating activation of NF-kappaB in trigeminal nucleus caudalis.

White matter lesions in chronic migraine with medication overuse headache: a cross-sectional MRI study.

Analgesic overuse often happens to migraine patients, especially chronic migraineurs, and migraine has been demonstrated to be associated with white matter lesions (WMLs). The aim of this study was to investigate the relationship between medication overuse headache (MOH) and WMLs in chronic migraine (CM) patients. Subjects were enrolled and divided into three groups: healthy controls, CM without MOH (CMwoMOH), and CM with MOH (CM-MOH). Most of the CM patients used non-steroidal anti-inflammatory drugs (NSAIDs) as acute headache medications. All the participants underwent magnetic resonance imaging scans and images were obtained for WML evaluation with semiquantitative scales. One hundred and forty-one participants were included, 45 of them for controls, 38 for CMwoMOH, and 58 for CM-MOH. In women, CMwoMOH patients had a higher prevalence of high WML load compared with controls and CM-MOH patients. In men, however, all the study groups showed no differences in the prevalence of high WML load. CMwoMOH women had increased risks of high deep white matter lesion (DWML) load compared with controls, while they had no risks of high periventricular white matter lesion (PVWML) load. CM-MOH women had no risks of high DWML load, but they had reduced risks of high PVWML load. The association of CM-MOH with high WML load in women was not changed when compared with CMwoMOH. Age was independently associated with high WML load among women. These data suggest that MOH caused by NSAIDs is not a risk factor for WMLs. Rather, NSAID overuse probably protects MOH patients from WMLs through anti-inflammatory effects.

Pregabalin alleviates the nitroglycerin-induced hyperalgesia in rats.

The association between the clinical use of nitroglycerin (NTG) and migraine suggests NTG as an animal model trigger for migraine. NTG-induced hyperalgesia in rats has been extensively used as a migraine model for pre-clinical research. Pregabalin is an anti-epileptic drug and may play a role in the preventive treatment of migraine; however, the mechanism of this action remains to be clarified. Herein, we performed the present study to investigate the effect of pregabalin on the NTG-induced hyperalgesia in rats. Sixty male Sprague-Dawley rats were divided equally into six groups. Thirty minutes before NTG injection, the rats were pretreated with pregabalin. von Frey hair testing was employed to evaluate tactile sensitivity. Enzyme-linked immunosorbent assay was used to analyze plasma calcitonin gene-related peptide (CGRP) levels in the jugular vein. Immunohistochemistry was applied to detect c-Fos-immunoreactive neurons and western blot was performed to detect c-Fos protein expression in trigeminal nucleus caudalis (TNC). We found that pregabalin pretreatment alleviated the NTG-induced hyperalgesia. Moreover, pregabalin suppressed peripheral CGRP release, c-Fos-immunoreactive neurons and the protein expression of c-Fos in TNC as well. These data suggest that pregabalin could alleviate the NTG-induced hyperalgesia. Further studies are required to determine the mechanisms of action for this effect.

Efficacy of intravenous propacetamol hydrochloride in the treatment of an acute attack of migraine.

BACKGROUND Triptans are a family of selective serotonin (5-HT1B/1D) receptor agonists that are widely used to treat acute migraine attacks. Their efficacy is limited by side effects and the gastrointestinal manifestations of migraine. AIM To compare the efficacy of a single intravenous administration of propacetamol, a prodrug of paracetamol (acetaminophen) with a single dose of oral rizatriptan in treating acute migraine attacks. METHODS Patients were selected from those who presented to the emergency room with a diagnosed migraine attack and who had not previously taken any analgesics. They were randomized into 2 groups: treatment with a single 1g IV dose of propacetamol or with a single oral dose of 5mg rizatriptan. Their Visual Analogue Scale (VAS) pain scores were assessed before and at 30, 60, and 120min after treatment. RESULTS The patients who received the propacetamol had significantly improved VAS scores at 60min compared to the rizatriptan group. There were no significant differences in VAS scores at 30 or 120min post-treatment. CONCLUSION Propacetamol is either equivalent or superior in efficacy to rizatriptan for treating acute migraine attacks, while having the advantage of parenteral administration in patients whose migraines are accompanied by nausea and vomiting.

Overuse of paracetamol caffeine aspirin powders affects cerebral glucose metabolism in chronic migraine patients.

Overuse of analgesic plays a prominent role in migraine chronification. Paracetamol caffeine aspirin (PCA) powders are commonly used in Chinese migraineurs. This study investigated the effects of the specific combination analgesic on cerebral glucose metabolism in chronic migraine (CM).