miR-181b promotes angiogenesis and neurological function recovery after ischemic stroke.

Promotion of new blood vessel formation is a new strategy for treating ischemic stroke. Non-coding miRNAs have been recently considered potential therapeutic targets for ischemic stroke. miR-181b has been shown to promote angiogenesis in hypoxia and traumatic brain injury model, while its effect on ischemic stroke remains elusive. In this study, we found that overexpression of miR-181b in brain microvascular endothelial cells subjected to oxygen-glucose deprivation in vitro restored cell proliferation and enhanced angiogenesis. In rat models of focal cerebral ischemia, overexpression of miR-181b reduced infarction volume, promoted angiogenesis in ischemic penumbra, and improved neurological function. We further investigated the molecular mechanism by which miR-181b participates in angiogenesis after ischemic stroke and found that miR-181b directly bound to the 3'-UTR of phosphatase and tensin homolog (PTEN) mRNA to induce PTEN downregulation, leading to activation of the protein kinase B (Akt) pathway, upregulated expression of vascular endothelial growth factors, down-regulated expression of endostatin, and promoted angiogenesis. Taken together, these results indicate that exogenous miR-181b exhibits neuroprotective effects on ischemic stroke through activating the PTEN/Akt signal pathway and promoting angiogenesis.

Naoxintong Capsule for Secondary Prevention of Ischemic Stroke: A Multicenter, Randomized, and Placebo-Controlled Trial.

OBJECTIVE: To examine whether the combination of Naoxintong Capsule with standard care could further reduce the recurrence of ischemic stroke without increasing the risk of severe bleeding. METHODS: A total of 23 Chinese medical centers participated in this trial. Adult patients with a history of ischemic stroke were randomly assigned in a 1:1 ratio using a block design to receive either Naoxintong Capsule (1.2 g orally, twice a day) or placebo in addition to standard care. The primary endpoint was recurrence of ischemic stroke within 2 years. Secondary outcomes included myocardial infarction, death due to recurrent ischemic stroke, and all-cause mortality. The safety of drugs was monitored. Results were analyzed using the intention-to-treat principle. RESULTS: A total of 2,200 patients were enrolled from March 2015 to March 2016, of whom 143 and 158 in the Naoxintong and placebo groups were lost to follow-up, respectively. Compared with the placebo group, the recurrence rate of ischemic stroke within 2 years was significantly lower in the Naoxintong group [6.5% vs. 9.5%, hazard ratio (HR): 0.665, 95% confidence interval (CI): 0.492-0.899, P=0.008]. The two groups showed no significant differences in the secondary outcomes and safety, including rates of severe hemorrhage, cerebral hemorrhage and subarachnoid hemorrhage (P>0.05). CONCLUSION: The combination of Naoxintong Capsule with standard care reduced the 2-year stroke recurrence rate in patients with ischemic stroke without increasing the risk of severe hemorrhage in high-risk patients. (Trial registration No. NCT02334969).

Systemic immune inflammation index and system inflammation response index are potential biomarkers of atrial fibrillation among the patients presenting with ischemic stroke.

BACKGROUND: Chronic inflammatory disorders in atrial fibrillation (AF) contribute to the onset of ischemic stroke. Systemic immune inflammation index (SIII) and system inflammation response index (SIRI) are the two novel and convenient measurements that are positively associated with body inflammation. However, little is known regarding the association between SIII/SIRI with the presence of AF among the patients with ischemic stroke. METHODS: A total of 526 ischemic stroke patients (173 with AF and 353 without AF) were consecutively enrolled in our study from January 2017 to June 2019. SIII and SIRI were measured in both groups. Logistic regression analysis was used to analyse the potential association between SIII/SIRI and the presence of AF. Finally, the correlation between hospitalization expenses, changes in the National Institutes of Health Stroke Scale (NIHSS) scores and SIII/SIRI values were measured. RESULTS: In patients with ischemic stroke, SIII and SIRI values were significantly higher in AF patients than in non-AF patients (all p < 0.001). Moreover, with increasing quartiles of SIII and SIRI in all patients, the proportion of patients with AF was higher than that of non-AF patients gradually. Logistic regression analyses demonstrated that log-transformed SIII and log-transformed SIRI were independently associated with the presence of AF in patients with ischemic stroke (log-transformed SIII: odds ratio [OR]: 1.047, 95% confidence interval CI = 0.322-1.105, p = 0.047; log-transformed SIRI: OR: 6.197, 95% CI = 2.196-17.484, p = 0.001). Finally, a positive correlation between hospitalization expenses, changes in the NIHSS scores and SIII/SIRI were found, which were more significant in patients with AF (all p < 0.05). CONCLUSIONS: Our study suggests SIII and SIRI are convenient and effective measurements for predicting the presence of AF in patients with ischemic stroke. Moreover, they were correlated with increased financial burden and poor short-term prognosis in AF patients presenting with ischemic stroke.

TMEM151A Variants Cause Paroxysmal Kinesigenic Dyskinesia: A Large-Sample Study.

BACKGROUND: Paroxysmal kinesigenic dyskinesia (PKD) is the most common type of paroxysmal dyskinesias. Only one-third of PKD patients are attributed to proline-rich transmembrane protein 2 (PRRT2) mutations. OBJECTIVE: We aimed to explore the potential causative gene for PKD. METHODS: A cohort of 196 PRRT2-negative PKD probands were enrolled for whole-exome sequencing (WES). Gene Ranking, Identification and Prediction Tool, a method of case-control analysis, was applied to identify the candidate genes. Another 325 PRRT2-negative PKD probands were subsequently screened with Sanger sequencing. RESULTS: Transmembrane Protein 151 (TMEM151A) variants were mainly clustered in PKD patients compared with the control groups. 24 heterozygous variants were detected in 25 of 521 probands (frequency = 4.80%), including 18 missense and 6 nonsense mutations. In 29 patients with TMEM151A variants, the ratio of male to female was 2.63:1 and the mean age of onset was 12.93 ± 3.15 years. Compared with PRRT2 mutation carriers, TMEM151A-related PKD were more common in sporadic PKD patients with pure phenotype. There was no significant difference in types of attack and treatment outcome between TMEM151A-positive and PRRT2-positive groups. CONCLUSIONS: We consolidated mutations in TMEM151A causing PKD with the aid of case-control analysis of a large-scale WES data, which broadens the genotypic spectrum of PKD. TMEM151A-related PKD were more common in sporadic cases and tended to present as pure phenotype with a late onset. Extensive functional studies are needed to enhance our understanding of the pathogenesis of TMEM151A-related PKD. © 2021 International Parkinson and Movement Disorder Society.

Examination of Structural Variations of the Circle of Willis by 3D Time-of-Flight Magnetic Resonance Angiography.

Objectives: To explore structural variations of the circle of Willis using three-dimensional time-of-flight magnetic resonance angiography (3D-TOF-MRA), and to compare this modality with digital subtraction angiography (DSA). Methods: A total of 819 consecutive patients suspected of having cerebral vascular diseases underwent 3D-TOF-MRA, followed by DSA within 2 weeks. We report accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 3D-TOF-MRA compared with DSA. Results: The sensitivity and specificity of combined analyses were 90-100 and 98-100%, respectively. The sensitivity and NPV of 3D-TOF-MRA images for A-, C-, D-, and H-types of circle of Willis anomalies were 100%. The specificity, accuracy and sensitivity were all 100% for detecting absence of the anterior communicating artery (ACOA). Sensitivity, specificity, PPV, and NPV were all 100% for detecting F-type. The sensitivity and PPV of volume rendered (VR) images for the B-, E-, and G-types were relatively low (85.0, 86.2, and 73.8%, respectively). Maximum intensity projection (MIP) was somewhat better (88.3, 89.2, and 81.8%, respectively). Combined analyses were better still (95.8, 96.1, and 99.0%, respectively). Specificity and NPVs were high (99.3-100%). Conclusions: 3D-TOF-MRA compares well to DSA for evaluation of the structure of the circle of Willis. As 3D-TOF-MRA is a non-invasive modality, it may be preferred as a means to evaluate structural variations of the circle of Willis.

Atherosclerosis in intracranial or extracranial vessels in diabetic patients and the association with stroke subtype.

BACKGROUND: Diabetes mellitus (DM) is associated with increased prevalence and severity of atherosclerosis. This study aimed to assess the prevalence and location of atherosclerosis in intracranial and extracranial vessels in diabetic patients and to investigate their association with ischemic stroke subtype. METHODS: Diabetes patients (n=128) and nondiabetic patients (n=195) were enrolled. Brain MRI, MR angiography, and digital subtraction angiography (DSA) imaging findings in the two groups were retrospectively compared. The characteristics of atherosclerosis (prevalence, location, severity) and collateral flow in diabetic and nondiabetic patients and their association with stroke subtype were analyzed. RESULTS: Atherosclerosis in extracranial vessels was more common in diabetes patients than in nondiabetic patients (43.8% vs. 23.1%; P<0.001). Symptomatic stenoses were commonly in the proximal internal carotid artery (ICA) and proximal vertebral artery (pVA). Diabetes patients were more likely to have lacunar infarction (49.2% vs. 32.3%; P=0.002) and less likely to have large artery infarct (36.7% vs. 48.2%; P=0.042). DM (OR, 2.03; 95% CI, 1.96-4.30; P=0.006) and age >65 years (OR, 2.55; 95% CI, 1.24-5.22; P=0.011) were independent risk factors for lacunar infarct. Diabetes patients with symptomatic extracranial stenosis or occlusion, combined with good collateral circulation, had significantly higher risk of lacunar infarction than nondiabetic patients (47.8% vs. 30.5%; P=0.045). CONCLUSIONS: DM aggravates the severity of extracranial atherosclerosis. Lacunar stroke is relatively common in diabetic patients and could even be due to large artery disease (LAD).

Dysregulated Urinary Arginine Metabolism in Older Adults With Amnestic Mild Cognitive Impairment.

Background: Urine samples, which capture an individual's metabolic profile, are ideal for the exploration of non-invasive biomarkers to confirm the amnestic mild cognitive impairment (aMCI) status of patients vs. unimpaired ones. Objective: We aimed to detect differentially metabolized amino acids, which are important objectives in metabolomics, garnering particular attention in biomedical pathogenesis from the urine of aMCI patients, which may give clinicians the possibility to intervene with early treatments that curb Alzheimer's disease (AD). Methods: The study included 208 subjects, 98 of whom were aMCI patients, and 110 who were control subjects without dementia. Urine samples were taken from each participant and supernatant was obtained for analysis. The concentrations of amino acids were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: Urinary arginine levels in aMCI patients are obviously lower than in normal controls (q < 0.2 and p < 0.05). Meanwhile, aMCI patients had significant reduced urinary global arginine bioavailability ratio (GABR), and GABR in urine displayed a positive correlation with the score of CMMSE. Conclusion: Urinary dysregulated arginine metabolism that may serve as a helpful clinical diagnostic biomarker for aMCI in older adults.

No inferiority of Tonbridge thrombectomy device for acute thrombus retrial compared with Solitaire device: an experimental evaluation with a canine distal external carotid-maxillary artery occlusion model.

INTRODUCTION: Mechanical thrombectomy (MT) has been widely accepted as a safe and effective treatment for acute ischemic stroke (AIS). Development of stent retriever devices has been intensively developed over the past two decades. In this study, we compared the effectiveness and safety of a new thrombectomy device with Solitaire FR for the treatment of AIS models. METHODS: Mechanical performance of stent retrievers was tested in vitro. Thrombin-induced thrombus was pre-injected into the right distal external carotid-maxillary artery in 18 dogs to create an acute thrombus occlusion model, and these animals were divided into a Tonbridge group (n=9, with Tonbridge stent Tonbridge Medical Technology) and a Solitaire group as control (n=9, with Solitaire stent, ev3 Neurovascular). Final flow restoration, side branches, recanalization time, distal vessel embolism, and device-related complications were recorded and compared. A post-procedure angiogram was obtained at 30 and 90 days after thrombectomy. Device manipulation-related damage to the arterial walls was evaluated histologically. RESULTS: In vitro test showed that the maximum friction within the microcatheter was 0.763 for the Tonbridge device and 0.784 n for the Solitaire (P>0.05). Slight increase in radial force was noticed for the Tonbridge (0.035 N/mm vs 0.031 N/mm of Solitaire, P>0.05). Eighteen and 16 retriever attempts were done in the Tonbridge (mean 2.0 attempts) and the Solitaire (mean 1.8 attempts) groups (P=0.74). The Tonbridge device led to good flow restoration in all nine (100%) models compared with eight (88.9%) in the Solitaire group (P=0.30). Side branches' influence (P=0.39), distal thromboembolism (P=0.60), and device-related complications (P=1.00) found no difference between the two groups. The rates of disruption of the internal elastic lamina (IEL) were 8.3% (2/24) and 4.2% (1/24) of the specimens, respectively (P=0.683). TICI 2b/3 flow of the right CCA were similar between the two groups at 1 (6/6 vs 6/6) and 3 months (6/6 vs 6/6) follow-up (P>0.05). CONCLUSION: Our preliminary study indicated this new device was technically feasible and effective to be used in thrombectomy for the treatment of acute thrombus occlusion in canine models.

Edaravone Attenuates the Proinflammatory Response in Amyloid-ß-Treated Microglia by Inhibiting NLRP3 Inflammasome-Mediated IL-1ß Secretion.

BACKGROUND/AIMS: Microglial activation is an important pathological feature in the brains of patients with Alzheimer's disease (AD), and amyloid-ß (Aß) peptides play a crucial role in microglial activation. In addition, edaravone (EDA) was recently shown to suppress oxidative stress and proinflammatory cytokine production in APPswePS1dE9 (APP/PS1) mice. However, the mechanism by which EDA inhibits the Aß-induced proinflammatory response in microglia is poorly understood. METHODS: The mitochondrial membrane potential (∆ψm) was evaluated using JC-1 staining. Intracellular reactive oxygen species (ROS) and mitochondrial ROS levels were detected using CM-H2DCFDA and MitoSOXTM Red, respectively. The levels of CD11b, NLRP3, pro-caspase-1 and manganese superoxide dismutase (SOD-2) were observed by western blotting, and the levels of interleukin-1beta (IL-1ß) in culture supernatants were quantified using an ELISA kit. RESULTS: Aß induced microglia activation and mitochondrial dysfunction. In addition, mitochondrial dysfunction was associated with ROS accumulation and activation of the NLRP3 inflammasome. Importantly, Aß induced activation of the NLRP3 inflammasome, leading to caspase-1 activation and IL-1ß release in microglia. Moreover, EDA obviously attenuated the depolarization of ∆ψm, reduced mitochondria-derived ROS production and increased SOD-2 activity, resulting in the suppression of NLRP3 inflammasome-mediated IL-1ß secretion in Aß-treated microglia. CONCLUSION: EDA is a mitochondria-targeted antioxidant and exhibits anti-inflammatory effects on Aß-treated microglia.

MRI based thrombolysis for FLAIR-negative stroke patients within 4.5-6h after symptom onset.

To investigate the feasibility of DWI-FLAIR mismatch in identifying patients who might benefit from thrombolytic therapy within 4.5-6h, we analyzed the data of 105 ischemic stroke patients with known time of symptom onset who underwent MRI within 6h of stroke and thrombolysis between December 2006 and December 2013. They were divided into three groups: symptom onset within 4.5h (n=66); 4.5-6h and FLAIR images negative (n=9); and 4.5-6h and FLAIR images positive (n=30). Outcome of thrombolysis was assessed for each group by recanalization rate, National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) scores. The results showed that mismatch between positive DWI and negative FLAIR images identified patients within 4.5h of symptom onset with sensitivity, specificity, positive predictive value and negative predictive value of 40.9%, 76.9%, and 75% and 43.5%. Recanalization rate, NIHSS score and mRS score were all better in both the 0-4.5h and 4.5-6h FLAIR-negative groups than in the 4.5-6h FLAIR-positive group (p<0.05). These data demonstrate that within 4.5-6h of symptom onset, patients with negative FLAIR images may benefit from thrombolysis therapy.

Efficacy and safety comparison of DL-3-n-butylphthalide and Cerebrolysin: Effects on neurological and behavioral outcomes in acute ischemic stroke.

Cerebrolysin and DL-3-n-butylphthalide (NBP) have each shown neuroprotective efficacy in preclinical models of acute ischemic stroke (AIS) and passed clinical trials as therapeutic drugs for AIS. The present study was a clinical trial to assess and compare the efficacy and safety of NBP and Cerebrolysin in the reduction of neurological and behavioral disability following AIS. A randomized, double-blind trial was conducted with enrolment of 60 patients within 12 h of AIS. In addition to routine treatment, patients were randomly assigned to receive a 10-day intravenous administration of NBP, Cerebrolysin or placebo. National Institutes of Health Stroke Scale (NIHSS) and Barthel Index (BI) scores were used to evaluate the efficacy of the treatment in the patients with AIS at 11 and 21 days after the initiation of therapy. Adverse events were also analyzed among the three groups. After 10 days of treatment with NBP or Cerebrolysin, the NIHSS and BI scores at day 21 showed statistical differences compared with those in the placebo group (P<0.05). The improvements of NIHSS and BI scores in the NBP and Cerebrolysin groups were higher than those in the placebo group at days 11 and 21 (P<0.05). A statistically significant difference in the improvement of 21-day NIHSS scores was observed between the two treatment groups (P<0.05). No significant difference was found among the three groups with regard to the rate of adverse events. Favorable outcomes and good safety were observed in the patients with moderate AIS treated with NBP or Cerebrolysin. The results indicate that NBP may be more effective than Cerebrolysin in improving short-term outcomes following AIS. This trial is registered at ClinicalTrials.gov with clinical trial identifier number NCT02149875.

The serum levels of MMP-9, MMP-2 and vWF in patients with low doses of urokinase peritoneal dialysis decreased uremia complicated with cerebral infarction.

To investigate the effect of MMP-9, MMP-2 and vWF in patients with low doses of urokinase peritoneal dialysis decreased uremia complicated with cerebral infarction. 112 cases of uremia complicated with cerebral infarction were randomly divided into the peritoneal dialysate with urokinase treatment group (66 cases) and the conventional treatment group (46 cases). At the same time, 50 cases of healthy people who were more than 45 years old were enrolled in the control group. The basic treatment in both treatment groups was the same. In urokinase therapy group based on the conventional treatment, urokinase was added into peritoneal dialysis fluid, and changes of serum MMP-9, MMP-2 and vWF were observed by drawing blood at different time points within 8 weeks. The changes of serum MMP-2, MMP-9 and vWF were detected by enzyme-linked immunosorbent assay. At the time of the onset of uremia complicated with cerebral infarction patients the serum MMP-9, MMP-2, vWF were significantly higher (P<0.05, P<0.05, P<0.01). Conventional antiplatelet therapy in brain protection only reduce MMP-9 to the normal range (P>0.05) within 8 weeks. But the MMP-2 and vWF cannot be reduced to the normal range (P<0.01, P<0.01). Low doses of urokinase can reduce MMP-9 (7 d) and MMP-2 (14 d) to the normal range (P>0.05, P>0.05) at the early stage and decrease the vWF to a normal range within 8 weeks (P>0.05). At the time of the onset of uremia complicated with cerebral infarction patients the serum MMP-9, MMP-2 and vWF increased significantly. Low doses of urokinase dialysis can reduce serum MMP-9, MMP-2, and vWF in acute uremia complicated with cerebral infarction without recurrence of cerebral infarction and cerebral hemorrhagic transformation, indicating that low dose of urokinase peritoneal dialysis may have a certain effect on the early treatment of this disease.

Sodium Chloride Increases Aß Levels by Suppressing Aß Clearance in Cultured Cells.

Recent studies suggest that high-salt diet is associated with cognitive decline in human and mouse. The fact that genetic factors account for less than 50% cases of sporadic Alzheimer's disease (AD) highlights the important contribution of environmental factors, such as high-salt diet, in AD pathogenesis. However, whether and how high-salt diet fits the "amyloid cascade" hypothesis remains unexplored. Here, we show sodium chloride (NaCl) could increase Aß levels in the medium of HEK293 cells overexpressing amyloid precursor protein (APP) or C99 fragment. NaCl treatment dose not affect APP level, gamma secretase level or activity. Instead, NaCl treatment suppresses the capacity of cells to clear Aß and reduces Apolipoprotein E (ApoE) level. Finally, NaCl treated THP-1 or BV2 cells are inefficient in clearing Aß when co-cultured with rat primary neurons. Our study suggests that high-salt diet may increase AD risk by directly modulating Aß levels.

Timing of recanalization and outcome in ischemic-stroke patients treated with recombinant tissue plasminogen activator.

BACKGROUND: Intravenous administration of recombinant tissue plasminogen activator (rtPA) is approved treatment for acute ischemic stroke <3 h of symptom onset. PURPOSE: To determine the impact of the timing and degree of recanalization on clinical outcome after rtPA infusion in patients. MATERIAL AND METHODS: Seventy-five patients with ischemic stroke in the middle cerebral artery territory treated with intravenous rtPA within 3 h were studied consecutively. Magnetic resonance imaging (MRI), including magnetic resonance angiography (MRA), before, 6 h, and 24 h after thrombolytic therapy was undertaken. Depending on the MRA results acquired 6 h after rtPA infusion, recanalization was graded as: early recanalization (ER), delayed recanalization (DR), and no recanalization (NR). Clinical outcome was assessed using the National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS). RESULTS: Of patients in the ER, DR and NR groups, 71.4% (15/21), 13.3% (2/15), and 30.7% (12/39), respectively, showed dramatic improvement in NIHSS score 7 days after rtPA administration compared with those scores upon hospital admission. The 6-h and 24-h NIHSS scores and 3-month mRS scores of ER patients were significantly lower than those of the other two groups (P < 0.05). The 24-h, 7-d NHISS and mRS scores of DR patients were significantly higher than NR patients (P = 0.001, 0.002, 0.049, respectively). Three patients in the DR group died during follow-up. CONCLUSION: These data suggest that DR is associated with clinical deterioration. Patients treated with rtPA thrombolysis should be under close observation for 6-24 h. Corresponding treatment should be considered once DR appears.

Guillain-Barré syndrome associated with Japanese encephalitis virus infection in China.

Abstract Guillain-Barré syndrome (GBS) is preceded by an infection in about two-thirds of patients. However, the infectious organism is often not identified. GBS secondary to Japanese encephalitis virus (JEV) infection has been reported only in India. Herein, we report a case of GBS preceded by JEV infection in China. A 23-year-old male had generalized weakness, numbness in the extremities, and bilateral facial nerve paralysis. One week prior, he had a high fever with headache, and several days later, he developed facial diplegia and sensory disturbances. Physical examination revealed facial diplegia and a weak gag reflex, quadriparesis more pronounced distally, generalized hyporeflexia, and no Babinski sign. JEV IgM and hepatitis B surface antibody (HbsAb) tests were positive. Other tests for hepatitis B infection were negative. Nerve electrophysiology suggested an acute demyelinating sensorimotor polyradiculoneuropathy. His cerebrospinal fluid was clear, the leukocyte count was 5 × 10(6)/L (normal range: 0-5 × 10(6)/L), protein 0.62 g/L (normal range: 0.15-0.45 g/L), and JEV IgM was weakly positive. He was diagnosed with GBS associated with a recent JEV infection. Intravenous (IV) immunoglobulins combined with IV methylprednisone was administered for 5 days, and at the 3-month follow-up, a complete neurological recovery was noted. GBS may be associated with JEV infection. GBS exhibits a good response to intravenous immunoglobulin or plasma exchange and has a good prognosis making prompt diagnosis important.

Glycogen synthase kinase-3 regulates production of amyloid-ß peptides and tau phosphorylation in diabetic rat brain.

The pathogenesis of diabetic neurological complications is not fully understood. Diabetes mellitus (DM) and Alzheimer's disease (AD) are characterized by amyloid deposits. Glycogen synthase kinase-3 (GSK-3) plays an important role in the pathogenesis of AD and DM. Here we tried to investigate the production of amyloid-ß peptides (A ß) and phosphorylation of microtubule-associated protein tau in DM rats and elucidate the role of GSK-3 and Akt (protein kinase B, PKB) in these processes. Streptozotocin injection-induced DM rats displayed an increased GSK-3 activity, decreased activity and expression of Akt. And A ß 40 and A ß 42 were found overproduced and the microtubule-associated protein tau was hyperphosphorylated in the hippocampus. Furthermore, selective inhibition of GSK-3 by lithium could attenuate the conditions of A ß overproduction and tau hyperphosphorylation. Taken together, our studies suggest that GSK-3 regulates both the production of A ß and the phosphorylation of tau in rat brain and may therefore contribute to DM caused AD-like neurological defects.

Clinicopathological features of Churg-Strauss syndrome with severe nerve degeneration: a case report.

Churg-Strauss syndrome (CSS) is a rare autoimmune vasculitis of unknown etiology that involves small- and medium-sized blood vessels. Its onset is thought to be associated with adult-onset asthma, and vasculitis typically involves vessels in the lungs. However, due to increased blood and tissue eosinophilia, vasculitis may result in the involvement multiple systems of (neurological, skin, etc.). We report a case of CSS with manifestations that included skin purpura and severe peripheral nerve degeneration in a 56-year-old woman with a recent history of asthma. After the treatment with methylprednisolone and standard immunosuppressive therapy, her rashes resolved, there were no acute asthma attacks, and the numbness in her lower limbs improved.

The -1123G>C variant of PTPN22 gene promoter is associated with latent autoimmune diabetes in adult Chinese Hans.

The protein tyrosine phosphatase non-receptor 22 (PTPN22) gene encodes for lymphoid protein tyrosine phosphatase. Recent studies demonstrated the association between the +1858T, -1123G>C variants of PTPN22 gene and type 1 diabetes mellitus in Caucasian and Japanese populations. This study examined the relationship between the polymorphism of PTPN22 gene and latent autoimmune 1 diabetes in adults (LADA) in Chinese Hans. We studied 229 adult Chinese patients with LADA (LADA group) and 210 healthy volunteers (control group). The -1123G>C and +1858C>T polymorphisms of PTPN22 gene were determined by PCR-restriction fragment length polymorphism method. Further, genotypic/allelic frequencies and clinical characteristics were compared between two groups. There was a significant difference of frequencies of the -1123G>C polymorphism between LADA and control groups (OR = 1.99, 95% CI = 1.24-3.2; P = 0.001). However, no significant differences in the +1858C>T genotypic (CC, CT) and allelic (C, T) frequencies were found. Furthermore, the frequencies of the -1123 GC, CC genotype in male patients with LADA were significantly higher compared with male healthy volunteers (OR = 1.65, 95% CI = 1.21-2.26; P = 0.005). The analysis of covariance demonstrated no difference between glycosylated hemoglobin, body mass index, duration of diabetes, C-peptide, and GAD-Ab titer between the group carrying GC/CC and the group without allele C. In conclusion, the -1123G>C promoter polymorphism of PTPN22 gene, but not the +1858C>T variant, is associated with LADA in adult Chinese Hans.

An experimental study of artificial murine bladder reflex arc established by abdominal reflex.

BACKGROUND: The neurogenic bladder dysfunction caused by spinal cord injury is difficult to treat clinically. The aim of this research was to establish an artificial bladder reflex arc in rats through abdominal reflex pathway above the level of spinal cord injury, reinnervate the neurogenic bladder and restore bladder micturition. METHODS: The outcome was achieved by intradural microanastomosis of the right T13 ventral root to S2 ventral root with autogenous nerve grafting, leaving the right T13 dorsal root intact. Long-term function of the reflex arc was assessed from nerve electrophysiological data and intravesical pressure tests during 8 months postoperation. Horseradish peroxidase (HRP) tracing was performed to observe the effectiveness of the artificial reflex. RESULTS: Single stimulus (3 mA, 0.3 ms pulses, 20 Hz, 5-second duration) on the right T13 dorsal root resulted in evoked action potentials, raised intravesical pressures and bladder smooth muscle, compound action potential recorded from the right vesical plexus before and after the spinal cord transaction injury between L5 and S4 segmental in 12 Sprague-Dawley rats. There were HRP labelled cells in T13 ventral horn on the experimental side and in the intermediolateral nucleus on both sides of the L6-S4 segments after HRP injection. There was no HRP labelled cell in T13 ventral horn on the control side. CONCLUSION: Using the surviving somatic reflex above the level of spinal cord injury to reconstruct the bladder autonomous reflex arc by intradural microanastomosis of ventral root with a segment of autologous nerve grafting is practical in rats and may have clinical applications for humans.

Unilateral amyloid-beta25-35 injection into the rat amygdala increases the expressions of aberrant tau phosphorylation kinases.

BACKGROUND: Neuropathologically, Alzheimer disease (AD) is characterized by the presence of extracellular plaques enriched in beta-amyloid peptides; however, the mechanism by which it results in the neurotoxicity is uncertain. The purpose of this study was to investigate whether it would prompt the progress of Alzheimer disease via enhancement of aberrant phosphorylated tau that results from its increased kinase gene expression. METHODS: Twenty-four male rats were divided into three groups, and each group had 8 rats: control, sham-operated, and Abeta(25-35) injected AD model groups. AD rat models were created by unilateral injections of Abeta(25-35) into the amygdala. The hyperphosphorylated tau protein was estimated by immunohistochemistry with paired helical filament-1 (PHF-1) antibody and paired helical filament-tau (AT8) antibody. The expressions of glycogen synthase kinase-3beta (GSK-3beta) and p38 mitogen-activated protein kinase (P(38)MAPK) mRNA were observed by in situ hybridization. RESULTS: Compared with the control and sham-operated groups, the evaluation of paired AT8 and paired helical filament-1 (PHF-1) in the cortexes and hippocampus of the AD model group showed the numbers of AT8 and PHF-1 positive cells, as well as the optical density (OD) values of the proteins were significantly higher (AT8: in CA2: 0.318 +/- 0.037 vs. 0.135 +/- 0.028, 0.136 +/- 0.031; in frontal cortex: 0.278 +/- 0.040 vs. 0.130 +/- 0.028, 0.190 +/- 0.037. PHF-1: in CA2: 0.386 +/- 0.034 vs. 0.139 +/- 0.010, 0.193 +/- 0.041; in frontal cortex: 0.395 +/- 0.050 vs. 0.159 +/- 0.030, 0.190 +/- 0.044, respectively, P < 0.01); the number of GSK-3beta mRNA and P(38)MAPK mRNA positive cells of the AD model group, as well as the OD values, also increased significantly in the cortexes, hippocampus (GSK-3beta-mRNA: in CA2: 0.384 +/- 0.012 vs. 0.190 +/- 0.015, 0.258 +/- 0.064; in frontal cortex: 0.398 +/- 0.018 vs. 0.184 +/- 0.031, 0.218 +/- 0.049. P(38)MAPK mRNA: in CA2: 0.409 +/- 0.038 vs. 0.161 +/- 0.041, 0.189 +/- 0.035; in frontal cortex: 0.423 +/- 0.070 vs. 0.160 +/- 0.032, 0.203 +/- 0.053, respectively, P < 0.01). CONCLUSION: Unilateral injection of Abeta(25-35) into the rat amygdala increases the generation of aberrant phosphorylated tau by increasing GSK-3beta and P(38)MAPK gene expression, that accelerates the process of Alzhemer's disease.