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Objective To examine the relationship between periodontitis and subclinical intracranial atherosclerosis. The association of periodontitis with preclinical markers of atherosclerosis in other vascular territories was also explored. Material and methods This was a cross-sectional study where 97 elderly subjects with a previous history of hypertension received an ultrasonographic evaluation to assess subclinical atherosclerosis in different vascular territories: (1) cerebral [pulsatility (PI) and resistance index (RI) of the middle cerebral artery], (2) carotid [intima-media thickness (IMT)], and (3) peripheral [ankle-brachial index (ABI)]. Additionally, participants underwent a full-mouth periodontal assessment together with blood sample collection to determine levels of inflammatory biomarkers (leukocytes, fibrinogen, and erythrocyte sedimentation rate), lipid fractions (total cholesterol and high- and low-density lipoprotein), and glucose. Results Sixty-one individuals had periodontitis. Compared to subjects without periodontitis, those with periodontitis showed higher values of PI (1.24 ± 0.29 vs 1.01 ± 0.16), RI (0.70 ± 0.14 vs 0.60 ± 0.06), and IMT (0.94 ± 0.15 vs 0.79 ± 0.15) (all p < 0.001). No statistically significant differences were found neither for ABI or for other clinical and biochemical parameters. An independent association was found between periodontitis and increased intracranial atherosclerosis (ORadjusted = 10.16; 95% CI: 3.14–32.90, p < 0.001) and to a lesser extent with thicker carotid IMT (ORadjusted = 4.10; 95% CI: 1.61–10.48, p = 0.003). Conclusions Periodontitis is associated with subclinical atherosclerosis in both intracranial and carotid arteries in elderly subjects with hypertension. Clinical relevance The association of periodontitis with intracranial atherosclerosis implies that periodontitis patients might have greater chances to develop ischemic stroke in the future.

Current pharmacological therapies for treating obesity are of limited efficacy. Genetic ablation or loss of function of AMP-activated protein kinase alpha 1 (AMPKα1) in steroidogenic factor 1 (SF1) neurons of the ventromedial nucleus of the hypothalamus (VMH) induces feeding-independent resistance to obesity due to sympathetic activation of brown adipose tissue (BAT) thermogenesis. Here, we show that body weight of obese mice can be reduced by intravenous injection of small extracellular vesicles (sEVs) delivering a plasmid encoding an AMPKα1 dominant negative mutant (AMPKα1-DN) targeted to VMH-SF1 neurons. The beneficial effect of SF1-AMPKα1-DN-loaded sEVs is feeding-independent and involves sympathetic nerve activation and increased UCP1-dependent thermogenesis in BAT. Our results underscore the potential of sEVs to specifically target AMPK in hypothalamic neurons and introduce a broader strategy to manipulate body weight and reduce obesity.

The National Institutes of Health Stroke Scale (NIHSS) is commonly used to evaluate stroke neurological deficits and to predict the patient’s outcome. Neurological instability (NI), defined as the variation of the NIHSS in the first 48 h, is a simple clinical metric that reflects dynamic changes in the area of the brain affected by the ischemia. We hypothesize that NI may represent areas of cerebral instability known as penumbra, which could expand or reduce brain injury and its associated neurological sequels. In this work, our aim was to analyze the association of NI with the functional outcome at 3 months and to study clinical biomarkers associated to NI as surrogate biomarkers of ischemic and inflammatory penumbrae in ischemic stroke (IS) patients. We included 663 IS patients in a retrospective observational study. Neutral NI was defined as a variation in the NI scale between − 5 and 5% (37.1%). Positive NI is attributed to patients with an improvement of > 5% NI after 48 h (48.9%), while negative NI is assigned to patients values lower than − 5% (14.0%). Poor outcome was assigned to patients with mRS ≥ 3 at 3 months. We observed an inverse association of poor outcome with positive NI (OR, 0.35; 95%CI, 0.18–0.67; p = 0.002) and a direct association with negative NI (OR, 6.30; 95%CI, 2.12–18.65; p = 0.001). Negative NI showed a higher association with poor outcome than most clinical markers. Regarding good functional outcome, positive NI was the marker with the higher association (19.31; CI 95%, 9.03–41.28; p

Background Wake-up ischemic stroke (IS) has been usually excluded from acute stroke therapy options for being outside of the safe treatment window. We identified risk factors, and clinical or molecular biomarkers that could be therapeutic targets for wake-up stroke prevention, thus hopefully leading to a decrease in its mortality and disability in medium to long-term outcome. Methods 4251 ischemic stroke (IS) patients from a prospectively registered database were recruited; 3838 (90.3%) had known onset-symptom time, and 413 (9.7%) were wake-up strokes. The main endpoint was to analyze the association between different serum biomarkers with wake-up IS episodes and their progression. Leukocytes count, serum levels of C-reactive protein, fibrinogen, interleukin 6 (IL-6), and vitamin D were analyzed as inflammation biomarkers; N-terminal pro-B-type Natriuretic-Peptide and microalbuminuria, used as atrial/endothelial dysfunction biomarkers; finally, glutamate levels as excitotoxicity biomarker. In addition, demographic, clinical and neuroimaging variables associated with the time-evolution of wake-up IS patients and functional outcome at 3 months were evaluated. Good and poor functional outcome were defined as mRS ≤2 and mRS > 2 at 3 months, respectively. Results Wake-up IS showed a poorer outcome at 3-months than in patients with known on-set-symptom time (59.1% vs. 48.1%; p p p p p = 0.394). No difference in DWI volume at admission was found (49.3 ± 96.9 ml in wake-up IS patients vs. 51.7 ± 98.2 ml in awake IS patients; p = 0.895). Conclusions Inflammatory biomarkers are the main factors that are strongly associated with wake-up IS episodes. Wake-up IS is associated with lower vitamin D levels. These data indicate that vitamin D deficiency could become a therapeutic target to reduce wake-up IS events.

Background Studying the impact of demographic changes and progress in the management of stroke patients is necessary in order to organize care structures for the coming years. Consequently, we analyzed the prognostic trends of patients admitted to the Stroke Unit of a tertiary hospital in the last ten years. Methods The University Clinical Hospital of Santiago de Compostela is the referral hospital for stroke in a catchment area that accounts for 16.5% of the population of Galicia. Data from patients admitted to the Stroke Unit were registered prospectively. A multinomial logistic regression was performed to determine the influence of new trends in demographic factors and in the management of patients with acute stroke. For the expected trend of progression, a 2008–2011 and 2012–2017 time series model was made by selecting the most appropriate model. Results In the last 10 years, the age of stroke onset has only increased in women (from 74.4 ± 2.2 years in 2008 to 78.8 ± 2.1 years in 2017; p = 0.037), and the same happens with the severity of neurological symptoms (ischemic stroke (IS), p