Nmnat1 Modulates Mitochondrial Oxidative Stress by Inhibiting Caspase-3 Signaling in Alzheimer's Disease.

Nigrostriatal pathway disturbance is one of the major pathogenic factors in Alzheimer's disease (AD). Dopaminergic neuron dysfunction results in bradykinesia and akinesia (inability to initiate movement), indicating a significant risk factor for substantia nigra pars compacta lesions. Furthermore, the nicotinamide adenine dinucleotide (NAD+) is associated with Aß toxicity decline in AD therapy. Nicotinamide mononucleotide adenylyltransferase 1 (Nmnat1) is an essential enzyme that preserves normal neuronal function and protects neurons from insult. This study aimed to investigate the potential therapeutic effects of Nmnat1 and its underlying mechanisms in a triple-transgenic mouse model of AD (3xTgAD). Results showed that Nmnat1 improved the substantial behavioral measures of cognitive impairments compared with the 3xTgAD control. Additionally, Nmnat1 overexpression significantly increased tyrosine hydroxylase-positive neurons and anti-apoptotic protein Bcl2 and caspase-3 expression levels in 3xTgAD mice. Nmnat1 also effectively controlled SOD1 activation. In conclusion, Nmnat1 substantially decreases multiple AD-associated pathological characteristics at least partially by the increase of caspase-3 activation.

Clinical characteristics and risk score for poor clinical outcome of acute ischemic stroke patients treated with intravenous thrombolysis therapy.

BACKGROUND: Tissue plasminogen activator (t-PA) is an effective therapy for acute ischemic stroke, but some patients still have poor clinical outcome. In this study, we investigated clinical characteristics of stroke patients and determined predictors for poor clinical outcome in response to t-PA treatment. METHODS: Clinical data from 247 patients were retrospectively reviewed. Clinical parameters that were associated with survival of patients were analyzed. Areas under receiver operating characteristic curves (ROC) were used to determine the feasibility of using various combinations of the clinical parameters to predict poor clinical response. The clinical outcome was defined according to the changes in Modified Rankin Scale. RESULTS: Overall, 145 patients had improved/complete recovery, 73 had no change, and 29 had worsening conditions or died during the in-clinic period. A univariate analysis showed that baseline characteristics including age, CRP, blood glucose level, systolic blood pressure, and admission NIHSS were significantly different (p < 0.05) among patients with different clinical outcome. A further multivariate analysis was then performed. Variables associated with poor clinical outcome (worsening/death) (p < 0.1) were included in the logistic regression model. Four parameters were retained in the model: Age, CRP, Blood glucose level, and Systolic blood pressure (ACBS). To allow a convenient usage of the ACBS classifier, the parameters were put into a scoring system, and the score at 7.7 was chosen as a cut-off. The ROC curve of this ACBS classifier has an area under the curve (AUC) of 0.7788, higher than other individual parameters. The ACBS classifier provided enhanced sensitivity of 69.2% and specificity of 74.3%. CONCLUSION: The ACBS classifier provided a satisfactory power in estimating the patients' clinical outcome. After further validating, the classifier may provide important information to clinicians for making clinical decisions.

Sensitivity and Specificity of Double-Track Sign in the Detection of Transverse Sinus Stenosis: A Multicenter Retrospective Study.

BACKGROUND: Transverse sinus stenosis (TSS) is common among patients with cerebral venous sinus thrombosis. No previous studies have reported on double-track sign detected on axial Gd-enhanced T1WI in TSS. This study aimed to determine the sensitivity and specificity of the double-track sign in the detection of TSS. METHODS: We retrospectively reviewed medical records of 383 patients with transverse sinus thrombosis (TST) and 30 patients with normal transverse sinus from 5 participating hospitals in china from January 2008 to June 2014. 167 feasible transverse sinuses included in this study were categorized into TSS (n = 76), transverse sinus occlusion (TSO) (n = 52) and transverse sinus normal (TSN) groups (n = 39) according to imaging diagnosis on digital subtraction angiography (DSA) or magnetic resonance venography (MRV). Double-track sign on axial Gd-enhanced T1WI was compared among the three groups. Sensitivity and specificity of double-track sign in detection of TSS were calculated, with final imaging diagnosis of TSS on DSA or MRV as the reference standard. RESULTS: Of 383 patients with TST recruited over a 6.5-year period, 128 patients were enrolled in the study, 255 patients were excluded because of insufficient clinical data, imaging finding and delay time, and 30 matched patients with normal transverse sinus were enrolled in the control group. Therefore, double-track sign assessment was conducted in 167 available transverse sinuses of 158 patients. Of the 76 sinuses in TSS group, 51 had double-track sign. Of the other 91 sinuses in TSO and TSN groups, 3 had a false-positive double-track sign. Thus, double-track sign on axial Gd-enhanced T1WI was 67.1% (95% CI 55.3-77.2) sensitive and 96.7% (95% CI 89.9-99.1) specific for detection of TSS. CONCLUSIONS: The double-track sign on axial Gd-enhanced T1WI is highly specific and moderate sensitive for detection of TSS. Nevertheless, it could be a direct sign and might provide an early clue for TSS.