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BACKGROUND: Cerebral stroke is a disease with a high disability rate and a high fatality rate. This study was undertaken to assess the risk of stroke associated pneumonia (SAP) in patients with ischemic stroke using A2DS2 score. METHODS: Altogether 1 279 patients with ischemic stroke who were treated in our department from 2009 to 2011 were retrospectively analyzed with A2DS2 score. A2DS2 score was calculated as follows: age ≥75 years=1, atrial fibrillation=1, dysphagia=2, male sex=1; stroke severity: NIHSS score 0-4=0, 5-15=3, ≥16=5. The patients were divided into three groups according to A2DS2 score: 620 in score 0 group, 383 in score 1-9 group, and 276 in score ≥10 group. The three groups were comparatively analyzed. The diagnostic criteria for SAP were as follows: newly emerging lesions or progressively infiltrating lesions on post-stroke chest images combined with more than two of the following clinical symptoms of infection: (1) fever ≥38 °C; (2) newly occurred cough, productive cough or exacerbation of preexisting respiratory tract symptoms with or without chest pain; (3) signs of pulmonary consolidation and/or wet rales; (4) peripheral white blood cell count ≥10×10(9)/L or ≤4×10(9)/L with or without nuclear shift to left, while excluding some diseases with clinical manifestations similar to pneumonia, such as tuberculosis, pulmonary tumors, non-infectious interstitial lung disease, pulmonary edema, pulmonary embolism and atelectasis. The incidence and mortality of SAP as well as the correlation with ischemic stroke site were analyzed in the three groups respectively. Mean± standard deviation was used to represent measurement data with normal distribution and Student's t test was used. The chi-square test was used to calculate the percentage for enumeration data. RESULTS: The incidence of SAP was significantly higher in the A2DS2 score≥10 group than that in the score 1-9 and score 0 groups (71.7% vs. 22.7%, 71.7% vs. 3.7%, respectively), whereas the mortality in the score≥10 group was significantly higher than that in the score 1-9 and score 0 groups (16.7% vs. 4.96%, 16.7% vs. 0.3%, respectively). The incidences of cerebral infarction in posterior circulation and cross-MCA, ACA distribution areas were significantly higher than those in the SAP group and in the non-SAP group (35.1% vs.10.1%, 11.4% vs. 7.5%, respectively). The incidence of non-fermentative bacteria infection was significantly increased in the score≥10 group. CONCLUSIONS: A2DS2 score provides a basis for risk stratification of SAP. The prevention of SAP needs to be strengthened in acute ischemic stroke patients with a A2DS2 score≥10.

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The calcium/calmodulin-dependent protein kinase kinase 2, adenosine monophosphate-activated protein kinase (CAMKK2-AMPK) pathway mediated amyloid ß42 (Aß42)-induced synaptotoxicity and blockage of CAMKK2-protected neurons against the effect of Aß42. Numerous microRNAs (miRNAs) were downregulated in response to Aß42, including miR-9, a synapse-enriched miRNA that is decreased in Alzheimer's disease. In the present study the effect of miR-9 on Aß42­triggered CAMKK2-AMPK activation and the synaptotoxic impairment was investigated. Aß42 oligomers were identified to be capable of inducing CAMKK2-AMPK pathway activation, which was attenuated by miR-9 overexpression. CAMKK2 was predicted to be a target of miR-9 using Pictar and Targetscan 6.2 Bioinformatics' algorithms. A luciferase activity assay and western blot analysis confirmed that miR-9 significantly inhibited CAMKK2 expression. Additionally, overexpression of miR-9 was sufficient to restore Aß42-induced dendritic spine loss and rescued Aß42-induced τ phosphorylation at Ser-262 mediated by the CAMKK2-AMPK pathway. The results of the present study demonstrated that miR-9 attenuated Aß-induced synaptotoxicity by targeting CAMKK2.

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Synaptic communication forms the basis of learning and memory. Disruptions of synaptic function and memory have been widely reported in many neurological diseases, such as dementia. Thus, restoration of impaired synaptic communication is a potential therapeutic approach for these diseases. In this study, we demonstrated that supplementation with berberine, a plant alkaloid with a long history of medicinal usage in Chinese medicine, effectively reverses the synaptic deficits induced by D-galactose. We also found that berberine rescued D-galactose-induced memory impairment and additionally rescued the mRNA and protein levels of Arc/Arg3.1, an important immediate early gene that is crucial for maintaining normal synaptic plasticity. Our study provides the first piece of evidence supporting the potential use of berberine in the treatment of neural diseases with synaptic/memory impairments.

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