Background and Purpose— Recanalization of the occluded artery is a primary goal in stroke treatment. Unfortunately, endovascular treatment is not always available, and tPA (tissue-type plasminogen activator) therapy is limited by its narrow therapeutic window; importantly, the rate of early arterial recanalization after tPA administration is low, especially for platelet-rich thrombi. The mechanisms for this tPA resistance are not well known. Since neutrophil extracellular traps (NETs) have been implicated in this setting, our aim was to study whether NET pharmacological modulation can reverse tPA resistance and the role of TLR4 (Toll-like receptor 4), previously related to NET formation, in thrombosis. Methods— To this goal, we have used a mouse photothrombotic stroke model, which produces a fibrin-free thrombus composed primarily of aggregated platelets and thrombi obtained from human stroke patients. Results— Our results demonstrate that (1) administration of DNase-I, which promotes NETs lysis, but not of tPA, recanalizes the occluded vessel improving photothrombotic stroke outcome; (2) a preventive treatment with Cl-amidine, impeding NET formation, completely precludes thrombotic occlusion; (3) platelet TLR4 mediates NET formation after photothrombotic stroke; and (4) ex vivo fresh platelet-rich thrombi from ischemic stroke patients are effectively lysed by DNase-I. Conclusions— Hence, our data open new avenues for recanalization of platelet-rich thrombi after stroke, especially to overcome tPA resistance.

Ischemic brain injury causes a local inflammatory response, involving the activation of resident brain cells such as microglia and the recruitment of infiltrating immune cells. Increasing evidence supports that plasticity of the myeloid cell lineage is determinant for the specific role of these cells on stroke outcome, from initiation and maintenance to resolution of post-ischemic inflammation. The aim of this review is to summarize some of the key characteristics of these cells and the mechanisms for their recruitment into the injured brain through interactions with platelets, endothelial cells and other leukocytes. Also, we discuss the existence of different leukocyte subsets in the ischemic tissue and, specifically, the impact of different myeloid phenotypes on stroke outcome, with special emphasis on neutrophils and their interplay with platelets. Knowledge of these cellular phenotypes and interactions may pave the way to new therapies able to promote protective immune responses and tissue repair after cerebral ischemia.

The diagnosis of dementia was highly accurate in this population-based, Spanish cohort study, and our prevalence figures agree with other European surveys. Given the high cost and difficulties of population rescreening and its relatively low yield, we conclude that a single 2-phase investigation (screening followed by clinical examination) provides accurate information for most population-based prevalence studies of dementia.

Background: In Spain, stroke is a major public health concern, but large population-based studies are scarce and date from the 1990s. We estimated the incidence and in-hospital mortality of stroke through a multicentered population-based stroke register in 5 geographical areas of Spain, i.e. Lugo, Almería, Segovia, Talavera de la Reina and Mallorca, representing north, south, central (×2) and Mediterranean areas of Spain, respectively, the aim and novelty being that all methodologies were standardized, and diagnoses were verified by a neurologist using neuroimaging techniques. Methods: The register identified subjects >17 years of age who suffered a first-ever stroke or transient ischemic attack (TIA) between 1 January and 31 December 2006. Stroke and TIA were defined according to the WHO criteria. The Lausanne Stroke Registry definitions were used to classify ischemic stroke subtypes, as follows: (1) large-artery atherosclerosis (LAA); (2) cardioembolism (CE); (3) lacunar stroke or small-artery occlusion (SAO); (4) stroke of other infrequent cause (SIC), and (5) stroke of undetermined cause (UND). We used several complementary data sources such as hospital discharge registers, emergency room registers and primary care surveillance systems. Results: In the 1-year study period, we identified 2,700 first-ever cerebrovascular episodes (53% men; 2,257 strokes + 443 TIA episodes). Brain CT in the acute stage was performed in 99% of cases. Of a total of 2,257 stroke patients, 1,817 (81%) had cerebral infarction, 350 (16%) had intracerebral hemorrhage, 59 (3%) had subarachnoid hemorrhage (SAH) and 31 (1%) had unclassifiable stroke. The overall unadjusted annual incidence for all cerebrovascular events was 187 per 100,000 [95% confidence interval (CI) 180–194; incidence for men: 202, 95% CI 189–210; incidence for women: 187, 95% CI 180–194]. The subtype of ischemic stroke could be determined in 1,779 patients and was classified as LAA in 624 (35%), CE in 352 (20%), SAO in 316 (18%), SIC in 56 (3%) and UND in 431 (24%). The incidence rates per 100,000 (95% CI) standardized to the 2006 European population were as follows: all cerebrovascular events, 176 (169–182); all stroke (non-TIA), 147 (140–153); TIA, 29 (26–32); ischemic stroke, 118 (112–123); intracerebral hemorrhage, 23 (21–26), and SAH, 4.2 (3.1–5.2). Incidence rates clearly increased with age in both genders, with a peak at or above 85 years of age. The in-hospital mortality was 14%. Conclusions: Our results show that the incidence of stroke and TIA in Spain is moderate compared to other Western and European countries. However, it is expected that these figures will change due to progressively aging populations.

Background: This study sought to describe stroke prevalence in Spanish elderly populations and compare it against that of other European countries.