Recommendations guide for experimental animal models in stroke research.

INTRODUCTION: The progress of effective therapies for stroke has become a challenging task for both researchers and clinicians. Some pitfalls in clinical trials might have their origins in the pre-clinical experimental ischaemic models for the evaluation of potential neuro-protective agents. METHODS: We aim to standardise the methods for the development of stroke animal models throughout Spain, to produce document with appropriate recommendations and best practice in order to improve experimental methods in the field of stroke research. RESULTS: Members of several experienced stroke research groups prepared a guide with recommendations in the application of focal cerebral ischaemic models. The main features of this guide are based on the selection of the most appropriate animal model, taking in account the objective of the study, the species, strain, age, sex of animals, as well as risk factors. The experimental design must include a sham control group and the sample size calculation. Animal randomisation and blind analysis, masked assessment of outcomes, monitoring of body temperature and cerebral blood flow, and the reporting of reasons for excluding animals from the study, as well as the mortality rate, are other main points to fulfil in the application of stroke models. CONCLUSIONS: Standardised methods are essential to increase the success of the pre-clinical findings in the stroke neuroprotection field to be able to translate to the clinical practice.

Diagnosis of canine echinococcosis: comparison of coproantigen and serum antibody tests with arecoline purgation in Uruguay.

Echinococcus granulosus is one of the most important and widespread of the helminth zoonoses. Diagnosis of E. granulosus infection in dogs currently relies on arecoline dosing and detailed examination of the purge for adult worms. Two immunodiagnostic tests (ELISA) based on genus specific coproantigen detection or serum antibody (IgG, IgA and IgE) detection were compared against arecoline purgation for the detection of Echinococcus in naturally infected dogs in Uruguay. The coproantigen ELISA had a sensitivity of 76.9% compared with 34.6% for the serum IgG ELISA when assessed against 26 purge positive dogs (purge worm count range 1-4331). Coproantigen reactivity was positively correlated (r = 0.65) to purge worm count, with a threshold at over 20 worms. There was no positive correlation of antibody levels with worm counts. In 26 matched Echinococcus positive dog samples, the overall sensitivity of serological detection increased to 69.2% when seroreactivity for IgA and IgE antibodies were included and to 96.2% for both coproantigen and antibody assays combined. The detection of current infection of individual dogs with E. granulosus by coproantigen ELISA has the potential to replace arecoline purgation, while specific serum antibody detection should be useful in assessing Echinococcus exposure in dog populations.

Echinococcus granulosus infections of dogs in the Durazno region of Uruguay.

The prevalence and distribution of Echinococcus granulosus in domestic dogs was examined in three dog populations in the Durazno region of Uruguay. The prevalence was 19.7 per cent in 704 dogs successfully purged with arecoline hydrobromide. Higher prevalences were detected in dogs from the rural area (30.0 per cent) and the village of La Paloma (25.9 per cent) than in the town of Sarandi del Yi (7.9 per cent). The frequency distribution of E granulosus was overdispersed (k, the negative binomial parameter = 0.08), with only a few animals harbouring heavy infections. The results of a questionnaire showed that the prevalence was greatest in male dogs, in dogs that were not kennelled, in dogs that had access to fields and in dogs that were not dosed with praziquantel. Dogs that were given raw sheep offal by their owners were no more likely to be parasitised than other dogs; this may reflect the inaccuracy of the owners' replies, or that the dogs were being infected outside their home.

[Prevalence of gallbladder lithiasis in a Uruguayan population]. / Prevalencia de litiasis vesicular en una población uruguaya.

Ultrasound examinations were carried out in 693 volunteers from the health care personnel of the Hospital de Clinicas of Montevideo, with the aim of studying the prevalence of gallbladder gallstones in Uruguay, the proportion of symptomatic and asymptomatic people and its association to some definite risk factors. The prevalence found was 10.4%, which, according to the sample's size, is representative of the general population with a confidence of 99%. Sixty five per cent of gallstones carriers were asymptomatic. A statistically significant association with the following factors was found: people between 31 and 50 years old, slight obesity, and, for women, to have children. A marked tendency with the following factors was found, though it was not statistically significant: female sex, and a familiar history of mother carrying gallstones. Considering all these factors as a whole, the probability of having gallstones reached 19%. Results are discussed and compared with those of foreign publications. It is concluded that uruguayan people with more possibilities of having gallstones are: women between 31 and 50 years old, obese, with children, and whose mother has or had the same disease.

[Imaging techniques for studying functional recovery following a stroke: I. Methodological aspects]. / Tecnicas de imagen para el estudio de la recuperacion funcional tras el ictus: I. Aspectos metodologicos.

Many patients that survive stroke have to face serious functional disabilities for the rest of their lives, which is a personal drama for themselves and their relatives, and an elevated charge for society. Thus functional recovery following stroke should be a key objective for the development of new therapeutic approaches. In this series of two works we review the strategies and tools available nowadays for the evaluation of multiple aspects related to brain function (both in humans and research animals), and how they are helping neuroscientist to better understand the processes of restoration and reorganization of brain function that are triggered following stroke. We have mainly focused on magnetic resonance applications, probably the most versatile neuroimaging technique available nowadays, and that everyday surprises us with new and exciting applications. But we tackle other alternative and complementary techniques, since a multidisciplinary approach allows a wider perspective over the underlying mechanisms behind tissue repair, plastic reorganization of the brain and compensatory mechanisms that are triggered after stroke. The first of the works of this series is focused on methodological aspects that will help us to understand how it is possible to assess brain function based on different physical and physiological principles. In the second work we will focus on different practical issues related to the application of the techniques here discussed.

[Comparison of the lesion produced by permanent focal cerebral ischaemia in three animal models using magnetic resonance imaging]. / Comparacion de la lesion producida en tres modelos animales de isquemia cerebral focal permanente mediante resonancia magnetica.

INTRODUCTION: Animal models of brain ischemia are essential to reveal the full aspects of cerebrovascular pathologies. The perfect animal model that reflects every aspect of stroke pathophysiology does not exist, hence there is a need for a proper selection of the animal model in order to interpret properly the results from experimental research. AIM: To characterize and compare the temporal evolution of three common models of focal brain ischemia using magnetic resonance imaging (MRI) techniques. MATERIALS AND METHODS: Thirty Sprague-Dawley rats were distributed into three groups, each of them submitted to one of the following surgery procedures: middle cerebral artery (MCA) intracranial suture, MCA electrocoagulation, and MCA intraluminal suture. Each rat was subjected to an MRI study at days 1, 2, 3, 4, 7 and 14 post-surgery. T2 weighted images were obtained in order to calculate both lesion volumes and edema. RESULTS: Infarct volume and edema were maximal for the intraluminal model (peaks of mean 297 ± 163 mm3 and mean 17 ± 9%, respectively) compared to intracranial suture (178 ± 62 mm3 and 9 ± 6%, respectively) and electrocoagulation (181 ± 45 mm3 and 9 ± 6%, respectively) models. DISCUSSION: The intraluminal occlusion of the MCA model, although yields in the highest mortality rate (28%), it is the more suitable for long term studies, mainly because of the absence of craniotomy. In the electrocoagulation model a non ischemic lesion region is observed which leads to an abnormal lesion evolution as compared with the other two models.

[Cognitive impairment associated to leukoaraiosis: its pathophysiology, clinical manifestations and treatment]. / Deterioro cognitivo asociado a la leucoaraiosis: fisiopatología, manifestaciones clínicas y tratamiento.

INTRODUCTION AND DEVELOPMENT: Leukoaraiosis is a radiological term which refers to white matter disturbances observed as a hypodensity in computed tomography and hyperintensity in T2-weighted magnetic resonance image. The most accepted theory to explain the mechanism of production of leukoaraiosis is chronic ischemia, due to a damage in penetrating arteries. It is an entity with increasing interest, since it is associated with the presence of cognitive impairment. Clinical manifestations in relation with cognitive functions range from mild affectation to dementia, affecting the processing speed and executive functions. CONCLUSIONS: It seems that the control of vascular risk factors slow the progression of leukoaraiosis and cognitive impairment, and although there are no really effective treatment, it seems that some drugs, such as acetylcholinesterase inhibitors or NMDA-receptor antagonists, exert a beneficial effect, although slight, in cognitive functions.

Prevalencia de litiasis vesicular en una poblacion uruguaya / Prevalence of gallbladder lithiasis in a Uruguayan population

Con el objetivo de conocer la prevalencia de L.V. en Uruguay, la proporción de sintomáticos y asintomáticos y su asociación a determinados factores de riesgo, se realizaron ecografías a 693 funcionarios del Hospital de Clínicas de Montevideo que concurrieron voluntariamente, previo llenado de un formulario. La prevalencia encontrada fue de 10,4%, de acuerdo al tamaño de la nuestra, extrapolable a la población general con una confianza del 99%. 65% de los portadores de L.V. fueron asintomáticos. Se encontró una asociación estadísticamente significativa con los siguientes factores: grupo etáreo de 31 a 50 años, obesidad leve y AP de tener hijos en caso de mujeres portadoras de la enfermedad. No fue estadísticamente significativo, pero si se comprobó una clara tendencia con los siguientes factores: sexo femenino y AF de madre portadora de L.V. Al considerar todos estos factores en conjunto, la probabilidad de tener una L.V. llegó al 19%. Se discuten los resultados y se comparan con los de publicaciones extranjeras. Se concluye que podía esbozarse un perfil del uruguayo con mayores posibilidades de tener una L.V.: mujer, entre 31 y 50 años, obesa, con hijos y cuya madre tuvo o tiene la misma enfermedad