Total rupture of Achilles tendon induces inflammatory response and glial activation on the spinal cord of mice

Rupture of Achilles tendon is a common accident affecting professional and recreational athletes. Acute and chronic pain are symptoms commonly observed in patients with rupture. However, few studies have investigated whether Achilles tendon rupture is able to promote disorders in the central nervous system (CNS). Therefore, the current study aimed to evaluate nociceptive alterations and inflammatory response in the L5 lumbar segment of Balb/c mice spinal cord after Achilles tendon rupture. We found increased algesia in the paw of the ruptured group on the 7th and 14th days post-tenotomy compared with the control group. This phenomenon was accompanied by overexpression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase-2 (NOS-2) as well as hyperactivation of astrocytes and microglia in nociceptive areas of L5 spinal cord as evidenced by intense GFAP and IBA-1 immunostaining, respectively. Biochemical studies also demonstrated increased levels of nitrite in the L5 spinal cord of tenotomized animals compared with the control group. Thus, we have demonstrated for the first time that total rupture of the Achilles tendon induced inflammatory response and nitrergic and glial activation in the CNS in the L5 spinal cord region.

Local inhibition of nitrergic activity in tenotomized rats accelerates muscle regeneration by increasing fiber area and decreasing central core lesions

Muscular atrophy is a progressive degeneration characterized by muscular proteolysis, loss of mass and decrease in fiber area. Tendon rupture induces muscular atrophy due to an intrinsic functional connection. Local inhibition of nitric oxide synthase (NOS) by Nω-nitro-L-arginine methyl ester (L-NAME) accelerates tendon histological recovery and induces functional improvement. Here we evaluate the effects of such local nitrergic inhibition on the pattern of soleus muscle regeneration after tenotomy. Adult male Wistar rats (240 to 280 g) were divided into four experimental groups: control (n=4), tenotomized (n=6), vehicle (n=6), and L-NAME (n=6). Muscular atrophy was induced by calcaneal tendon rupture in rats. Changes in muscle wet weight and total protein levels were determined by the Bradford method, and muscle fiber area and central core lesion (CCL) occurrence were evaluated by histochemical assays. Compared to tenotomized (69.3±22%) and vehicle groups (68.1%±17%), L-NAME treatment induced an increase in total protein level (108.3±21%) after 21 days post-injury. A reduction in fiber areas was observed in tenotomized (56.3±1.3%) and vehicle groups (53.9±3.9%). However, L-NAME treatment caused an increase in this parameter (69.3±1.6%). Such events were preceded by a remarkable reduction in the number of fibers with CCL in L-NAME-treated animals (12±2%), but not in tenotomized (21±2.5%) and vehicle groups (19.6±2.8%). Altogether, our data reveal that inhibition of tendon NOS contributed to the attenuation of atrophy and acceleration of muscle regeneration.

Therapeutic concentration of morphine reduces oxidative stress in glioma cell line

Morphine is a potent analgesic opioid used extensively for pain treatment. During the last decade, global consumption grew more than 4-fold. However, molecular mechanisms elicited by morphine are not totally understood. Thus, a growing literature indicates that there are additional actions to the analgesic effect. Previous studies about morphine and oxidative stress are controversial and used concentrations outside the range of clinical practice. Therefore, in this study, we hypothesized that a therapeutic concentration of morphine (1 μM) would show a protective effect in a traditional model of oxidative stress. We exposed the C6 glioma cell line to hydrogen peroxide (H2O2) and/or morphine for 24 h and evaluated cell viability, lipid peroxidation, and levels of sulfhydryl groups (an indicator of the redox state of the cell). Morphine did not prevent the decrease in cell viability provoked by H2O2 but partially prevented lipid peroxidation caused by 0.0025% H2O2 (a concentration allowing more than 90% cell viability). Interestingly, this opioid did not alter the increased levels of sulfhydryl groups produced by exposure to 0.0025% H2O2, opening the possibility that alternative molecular mechanisms (a direct scavenging activity or the inhibition of NAPDH oxidase) may explain the protective effect registered in the lipid peroxidation assay. Our results demonstrate, for the first time, that morphine in usual analgesic doses may contribute to minimizing oxidative stress in cells of glial origin. This study supports the importance of employing concentrations similar to those used in clinical practice for a better approximation between experimental models and the clinical setting.

Mercurio y neurotoxicidad / Mercury and neurotoxicity

Introducción y objetivo. El mercurio es un metal ampliamente utilizado hoy día en cientos de aplicaciones. Este metal ha demostrado ser sumamente tóxico para el ser humano, especialmente para el sistema nervioso central, tanto por la exposición a sus aplicaciones cotidianas (p. ej., las amalgamas dentales), como por exposiciones ambientales. Desdichadamente, la mayor parte de la investigación desarrollada sobre este metal es relativamente reciente, y quedan todavía muchos interrogantes por responder. El objetivo de este trabajo es revisar todo lo que se conoce hasta ahora sobre los mecanismos de acción de este metal. Desarrollo. Para ello, se discuten los hallazgos científicos más recientes sobre los procesos tóxicos activados, como las alteraciones en el citoesqueleto celular, la toxicidad genética o la producción de compuestos relacionadas con la neurodegeneración. Conclusiones. Un prolongado período de latencia, una sintomatología esquiva y la activación de mecanismos tóxicos generalizados, demandan urgentemente la aplicación de grandes esfuerzos en investigación básica para ayudarnos a discernir lo más claramente posible la forma de actuación de este metal. Este conocimiento nos proporcionará no sólo el camino para la obtención de terapias, sino la esperanza de desarrollar biomarcadores que posibiliten un diagnóstico precoz y fiable del daño producido y de la susceptibilidad individual

Introduction and aims. Mercury is a metal that is widely used in hundreds of applications nowadays. This metal has proved to be extremely toxic in humans, especially for the central nervous system, both in cases of exposure from everyday applications (e.g. dental fillings) and from environmental exposure. Unfortunately, most of the research carried out on this metal is relatively recent and many questions remain unanswered. The aim of this work is to review all the knowledge we have at the present time about the mechanisms of action of this metal. Development. To do so, we discuss the latest scientific findings about the toxic processes that are activated, as well as its effects on the cellular cytoskeleton, its genotoxicity or the production of compounds that have been linked to neurodegeneration. Conclusions. Its prolonged period of latency, ambiguous symptoms and the activation of generalised toxic mechanisms call for urgent efforts to be made in basic research to help determine as clearly as possible the way this metal acts in the body. This knowledge will provide us not only with the way to obtain therapies but also with the hope of developing biomarkers that make it possible to carry out early and reliable diagnoses of the damage done and of individual susceptibility