Ischemic strokes are major causes of death and disability. Searching for potential therapeutic strategies to prevent and treat stroke is necessary, given the increase in overall life expectancy. Epidemiological reports indicate that metformin is an oral antidiabetic medication that can reduce the incidence of ischemic events in patients with diabetes mellitus. Its mechanism of action has not been elucidated, but metformin pleiotropic effects involve actions in addition to glycemic control. AMPK activation has been described as one of the pharmacological mechanisms that explain the action of metformin and that lead to neuroprotective effects. Most experiments done in the cerebral ischemia model, via middle cerebral artery occlusion in rodents (MCAO), had positive results favoring metformin's neuroprotective role and involve several cellular pathways like oxidative stress, endothelial nitric oxide synthase activation, activation of angiogenesis and neurogenesis, autophagia, and apoptosis. We will review the pharmacological properties of metformin and its possible mechanisms that lead to neuroprotection in cerebral ischemia.

Introducción. En la medicina tradicional colombiana se usa la infusión de toda la planta llamada "mastranto" u "oreja de perro" (Salvia scutellarioides) por sus efectos antihipertensivos y diuréticos. Hasta ahora no se han hecho estudios experimentales para validar los efectos reportados. Objetivos. Determinar el efecto de S. scutellarioides en la diuresis y concentración de electrolitos urinarios utilizando un modelo en ratas. Materiales y métodos. Veinticuatro ratas Sprague-Dawley machos fueron repartidas al azar en cuatro grupos homogéneos: el grupo 1 recibió solución salina normal; el grupo 2, furosemida (10 mg/kg), y los grupos 3 y 4, S. scutellarioides (1 g/kg y 2 g/kg, respectivamente). Todos los tratamientos se administraron en un volumen de 25 ml/kg de peso del animal. Las ratas se colocaron en una jaula metabólica durante seis horas, y se cuantificó la excreción urinaria y los electrolitos en orina. Resultados. La administración de S. scutellarioides en dosis de 1 y 2 g/kg produjo un aumento significativo de la diuresis comparado con la del grupo control (p<0,01). El efecto diurético se manifestó principalmente a partir de la cuarta hora de administración de S. scutellarioides. La administración de S. scutellarioides en ambas dosis produjo un incremento en la excreción urinaria de potasio y cloro. Conclusiones. El estudio corrobora la aparente actividad diurética de S. scutellarioides reportada por médicos tradicionales, lo que podría explicar su posible efecto antihipertensivo. Se requieren más estudios para determinar el perfil farmacológico y la toxicidad de la planta.Palabras clave: diuréticos, Lamiaceae, Salvia, etnofarmacología, fitoterapia, medicina herbaria. Diuretic effect of an infusion of the herbal plant, Salvia scutellarioides, in rats.Introduction. In the Colombian traditional medicine, an infusion made of the entire plant Salvia scutellarioides (known locally as mastranto or oreja de perro (dog's ear)) is used for its antihypertensive and diuretic effects. However, experimental studies have never been done to validate the reported effects. Objective. In the current study, a rat model was used to determine the effect of S. scutellarioides on rat diuresis and urinary electrolytes concentration. Materials and methods. Twenty-four male Sprague-Dawley rats were distributed in four groups: Group 1-normal saline solution, Group 2-furosemide (10mg/kg), Groups 3 and 4 with S. scutellarioides infusion, 1g/kg and 2g/kg respectively. All treatments were administered in a volume of 25ml/kg of rat weight. After treatment, the rats were placed in a metabolic cage for 6 hours. During this period, urinary excretion was monitored and quantified. At the end of 6 hours, the urinary electrolyte concentrations were measured. Results. The administration of S. scutellarioides at doses of 1 and 2 g/kg produced a significant increase in diuresis when compared to the control group (p<0.01). The administration of S. scutellarioides at these doses also increased the urinary excretion of potassium and chloride. Concl...

The acute and subacute toxicity of the aqueous extract of Salvia scutellarioides (Lamiaceae) was studied in mice and rats. In the acute toxicity test, oral administration of 2g/kg of Salvia scutellarioides produced neither mortality nor changes in behavior or any other physiological activities. In subacute toxicity studies, no mortality was observed when the two doses of 1 or 2g/kgday of aqueous extract of Salvia scutellarioides extract were administered orally for a period of 28 days. In the blood chemistry analysis, no significant changes occurred, including glucose, creatinine, blood urea nitrogen (BUN), aspartate transaminase (AST), alanine transaminase (ALT), potassium, sodium, chloride, calcium, phosphorus, conjugated billirrubin, total billirrubin, total cholesterol, high density lipoprotein (HDL), triglycerides, total protein, albumin, prothrombin time (PT) and thromboplastin partial time (PTT) of both sexes. Hematological analysis showed no differences in any of the parameters examined (WBC count, platelet and hemoglobin estimation) in either the control or treated group of both sexes. The urinalysis was negative for glucose, ketonic bodies, casts, red blood cells, and albumin in the control and treatment groups. There were no significant differences in the body and organ weights between controls and treated animals of both sexes. Pathologically, neither gross abnormalities nor histopathological changes were observed.

The principal aim in the management of patients with cerebral contusion (CC) following severe traumatic brain injury (TBI) is the prevention, amelioration, and treatment of secondary neuronal dysfunction and pathology. Distinguishing between irreversibly damaged and surviving tissue could have considerable therapeutic and prognostic implications for patients. To characterize structurally the neuronal compartment of the contused region in samples derived from patients who suffered severe TBI and were subjected to decompressive craniectomy, we used NeuN, a neuronal marker. We determined that NeuN "patches", sectors with loss of NeuN immunoreactivity (NeuN-IR), represented 25% of the area among the analyzed cases. We also found a 67% decrease in NeuN levels via Western blot. Tissue adjoining patches of NeuN-IR were considered "preserved" due to the apparent normal density of neurons and conservation of the six cortical layers. Nevertheless, these sectors retained only 39% of their neurons with the classical pattern described for normal NeuN-IR. Using Fluorojade we identified a 16-fold increase in density of moribund neurons in "preserved" sectors when compared to controls. Additionally these abnormalities were enhanced 5-fold in "patches" of NeuN-IR when compared to preserved regions. Therefore, NeuN/Fluorojade abnormalities are indicative of different cell fates characteristic of CC tissue. This analysis addressed exclusively the neuronal compartment and provides new insights into the degenerative state of neurons in the contused region that is likely to contribute to clinical outcome and differentiate TBI from ischemia.

Most of the medical practice has not been proven by controlled clinical trials, and there are no plans to conduct such trials in order to decrease clinician uncertainty. This happens partly due to the difficulty of making designs with scientific and ethical validity, the costs of this type of research and the time required to generate results, which can be several years. Clinical trials do not have the capability to generate information that allows to make decisions in some sectors of clinical care and public health, such as when an epidemic occurs. Therefore, medical science is based on observational studies, past practices and therapeutic tradition (1). Observation of clinical data that have defined a clinical behavior precedes the clinical trial. The knowledge about scurvy, the fact that this pathology is considered a nutritional deficiency and its treatment with citrus fruits, originated thanks to the collection of clinical data on sailors, soldiers and prisoners of the British Crown in the 18th and 19th centuries (2). This clinical information, which was collected uniformly and served to produce new knowledge, is what is now known as Real World Data (RWD). A modern definition of RWD would be one that talks about data obtained by any non-interventionist methodology that is collected prospectively and retrospectively from observations of routine clinical practice, and which comes from various sources including data from patients, doctors, hospitals, payers, social data, etc (3).

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