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Hypertension is a main risk factor for the development of cerebral small vessel disease ( cSVD) - a major contributor to stroke and the most common cause of vascular dementia. Despite the increasing socioeconomic importance arising from cSVD, currently only a few specific treatment strategies with proven efficacy are known. Fundamental to the lack of specific treatments is poor understanding of the disease pathogenesis and a lack of appropriate animal models resembling all symptoms of the human disease. However, chronic hypertensive rat models have been shown to bear similarities to most key features of cSVD. Despite a significantly larger toolbox available for genotypic and phenotypic modifications compared to rats, mouse models of hypertension are unusual when modeling cSVD and associated cognitive impairment experimentally. In the present study, we therefore characterized hypertension-mediated cerebrovascular alterations and accompanying structural and functional consequences by simultaneously treating adult wild-type mice (C57 BL/6N) with Angiotensin II (Ang II) and the nitric oxide synthases inhibitor L- NAME for 4 weeks. Hypertension associated to cerebral alterations reminiscent of early-onset cSVD and vascular cognitive impairment when combined with additional Ang II bolus injections. Most importantly, preventing the elevation of blood pressure ( BP) protected from the development of cSVD symptoms and associated cognitive decline. Our data strongly support the suitability of this particular mouse model of Ang II-induced hypertension as an appropriate animal model for early-onset cSVD and hence, vascular cognitive impairment, pathologies commonly preceding vascular dementia. [ABSTRACT FROM AUTHOR]

Background and Purpose: Computed tomography perfusion (CTP) has a high diagnostic value in the detection of acute ischemic stroke in the anterior circulation. However, the diagnostic value in suspected posterior circulation (PC) stroke is uncertain, and whole brain volume perfusion is not yet in widespread use. We therefore studied the additional value of whole brain volume perfusion to non-contrast CT (NCCT) and CT angiography source images (CTA-SI) for infarct detection in patients with suspected acute ischemic PC stroke. Methods: This is a retrospective review of patients with suspected stroke in the PC in a database of our stroke center (n = 3,011) who underwent NCCT, CTA and CTP within 9 h after stroke onset and CT or MRI on follow-up. Images were evaluated for signs and pc-ASPECTS locations of ischemia. Three imaging models - A (NCCT), B (NCCT + CTA-SI) and C (NCCT + CTA-SI + CTP) - were compared with regard to the misclassification rate relative to gold standard (infarction in follow-up imaging) using the McNemar's test. Results: Of 3,011 stroke patients, 267 patients had a suspected stroke in the PC and 188 patients (70.4%) evidenced a PC infarct on follow-up imaging. The sensitivity of Model C (76.6%) was higher compared with that of Model A (21.3%) and Model B (43.6%). CTP detected significantly more ischemic lesions, especially in the cerebellum, posterior cerebral artery territory and thalami. Conclusions: Our findings in a large cohort of consecutive patients show that CTP detects significantly more ischemic strokes in the PC than CTA and NCCT alone. [ABSTRACT FROM AUTHOR]

Omitting quality characteristics in animal stroke studies leads to an overestimation of the efficacy of candidate stroke drugs. Nevertheless, the methodological quality of preclinical stroke studies is often limited. As publishing of research results in high-impact journals is an important motivation for scientists, we analyzed whether study quality predicts high-impact publishing. Animal stroke studies of neuroprotective drugs that were recently investigated in clinical phase II/III trials were included in the analysis. Data on the study quality and other important study characteristics were extracted. Regression analyses were performed to estimate the effect of the study characteristics on the journal's impact factor. We identified 117 studies that investigated 12 different drugs. Study quality was not associated with the impact factor before (β=−0.2, P=0.50) and after adjustment for other study characteristics (β=−0.3, P=0.19). There was a significant association of the number of investigated mechanisms and applied techniques with the impact factor (β=1.4, P<0.0001). Our findings show that the quality of animal experimental stroke studies is not relevant for publishing in high-impact journals. The major predictor for accepting preclinical stroke studies in high-impact journals is the complexity of the investigation into a stroke drug's mode of action. [ABSTRACT FROM AUTHOR]

Background: We have previously identified Semaphorin 6a (Sema6A) as an upregulated gene product in a gene expression screen in cortical ischemia [1]. Semaphorin 6a was regulated during the recovery phase following ischemia in the cortex. Semaphorin 6a is a member of the superfamily of semaphorins involved in axon guidance and other functions. We hypothesized that the upregulation indicates a crucial role of this molecule in post-stroke rewiring of the brain. Here we have tested this hypothesis by overexpressing semaphorin 6a in the cortex by microinjection of a modified AAV2-virus. A circumscribed cortical infarct was induced, and the recovery of rats monitored for up to 4 weeks using a well-established test battery (accelerated rotarod training paradigm, cylinder test, adhesive tape removal). We observed a significant improvement in post-ischemic recovery of animals injected with the semaphorin 6a virus versus animals treated with a control virus. We conclude that semaphorin 6a overexpressed in the cortex enhances recovery after cerebral ischemia. Semaphorin 6a may represent a novel therapeutic candidate for the treatment of chronic stroke. [ABSTRACT FROM AUTHOR]

Objectives Infections in patients with stroke are common and significantly affect outcome. Various predictors of poststroke infections were determined, such as degree of neurological impairment and implementation of therapeutic interventions. The authors investigated whether stroke location and stroke size are independent risk factors for poststroke infections. Methods 591 patients with acute stroke who were treated on our stroke unit were included in a prospective observational study. Predefined endpoints were pneumonia, urinary-tract infection (UTI) and other infections. The OR of infections was calculated for various stroke locations, stroke lateralisation and three categories of stroke size. Logistic regression models were used to adjust for factors significantly associated with poststroke infections in a single-factor analysis. Results In the single-factor analysis, the left anterior cerebral artery territory was associated with pneumonia. After adjustment for relevant covariates, this association was no longer statistically significant. Stroke lateralisation showed no association with infection frequency. The largest stroke size was positively associated with pneumonia (OR 3.5, p<0.001). The smallest lesion size was significantly less associated with the occurrence of UTI (OR 0.4, p<0.01). Conclusion In this study, lesion size is an independent risk factor for the development of poststroke infection. Particular brain regions associated with infections could not be determined. [ABSTRACT FROM AUTHOR]

Summary: Ischemic stroke causes brain damage by multiple pathways. Previous stroke trials have demonstrated that drugs targeting one or only a few of these pathways fail to improve clinical outcome after stroke. Drugs with multimodal actions have been suggested to overcome this challenge. In this review, we describe the mechanisms of action of agents approved for secondary prevention of ischemic stroke, such as antiplatelet, antihypertensive, and lipid-lowering drugs. These drugs exhibit considerable properties beyond their classical mechanisms, including neuroprotective and neuroregenerative properties. In addition, candidate stroke drugs currently studied in clinical phase III trials are described. Among these, albumin, hematopoietic growth factors, and citicoline have been identified as promising agents with multiple mechanisms. These drugs offer hope that additional treatment options for the acute phase after a stroke will become available in the near future. [Copyright &y& Elsevier]

A letter to the editor is presented on the importance of A Very Early Rehabilitation Trial for Stroke (AVERT) to translational stroke research.