Cocaine promotes oxidative stress and microglial-macrophage activation in rat cerebellum

Different mechanisms have been suggested for cocaine neurotoxicity, including oxidative stress alterations. Nuclear factor kappa B (NF-κB), considered a sensor of oxidative stress and inflammation, is involved in drug toxicity and addiction. NF-κB is a key mediator for immune responses that induces microglial/macrophage activation under inflammatory processes and neuronal injury/degeneration. Although cerebellum is commonly associated to motor control, muscular tone, and balance. Its relation with addiction is getting relevance, being associated to compulsive and perseverative behaviors. Some reports indicate that cerebellar microglial activation induced by cannabis or ethanol, promote cerebellar alterations and these alterations could be associated to addictive-related behaviors. After considering the effects of some drugs on cerebellum, the aim of the present work analyzes pro-inflammatory changes after cocaine exposure. Rats received daily 15 mg/kg cocaine i.p., for 18 days. Reduced and oxidized forms of glutathione (GSH) and oxidized glutathione (GSSG), glutathione peroxidase (GPx) activity and glutamate were determined in cerebellar homogenates. NF-κB activity, CD68, and GFAP expression were determined. Cerebellar GPx activity and GSH/GSSG ratio are significantly decreased after cocaine exposure. A significant increase of glutamate concentration is also observed. Interestingly, increased NF-κB activity is also accompanied by an increased expression of the lysosomal mononuclear phagocytic marker ED1 without GFAP alterations. Current trends in addiction biology are focusing on the role of cerebellum on addictive behaviors. Cocaine-induced cerebellar changes described herein fit with previosus data showing cerebellar alterations on addict subjects and support the proposed role of cerebelum in addiction

Image_1_Lipoic Acid and Progesterone Alone or in Combination Ameliorate Retinal Degeneration in an Experimental Model of Hereditary Retinal Degeneration.tif

<p>Retinitis pigmentosa (RP) is a group of inherited retinopathies characterized by photoreceptors death. Our group has shown the positive progesterone (P4) actions on cell death progression in an experimental model of RP. In an effort to enhance the beneficial effects of P4, the aim of this study was to combine P4 treatment with an antioxidant [lipoic acid (LA)] in the rd1 mice. rd1 and control mice were treated with 100 mg/kg body weight of P4, LA, or a combination of both on postnatal day 7 (PN7), 9, and 11, and were sacrificed at PN11. The administration of LA and/or P4 diminishes cell death in rd1 retinas. The effect obtained after the combined administration of LA and P4 is higher than the one obtained with LA or P4 alone. The three treatments decreased GFAP staining, however, in the far peripheral retina, and the two treatments that offered better results were LA and LA plus P4. LA or LA plus P4 increased retinal glutathione (GSH) concentration in the rd1 mice. Although LA and P4 are able to protect photoreceptors from death in rd1 mice retinas, a better effectiveness is achieved when administering LA and P4 at the same time.</p

Quantification of Microvascular Lesions in the Central Retinal Field: Could It Predict the Severity of Diabetic Retinopathy?

Diabetic retinopathy (DR) is a neurodegenerative disease characterized by the presence of microcirculatory lesions. Among them, microaneurysms (MAs) are the first observable hallmark of early ophthalmological changes. The present work aims to study whether the quantification of MAs, hemorrhages (Hmas) and hard exudates (HEs) in the central retinal field could have a predictive value on DR severity. These retinal lesions were quantified in a single field NM-1 of 160 retinographies of diabetic patients from the IOBA’s reading center. Samples included different disease severity levels and excluded proliferating forms: no DR (n = 30), mild non-proliferative (n = 30), moderate (n = 50) and severe (n = 50). Quantification of MAs, Hmas, and HEs revealed an increasing trend as DR severity progresses. Differences between severity levels were statistically significant, suggesting that the analysis of the central field provides valuable information on severity level and could be used as a clinical tool to assess DR grading in the eyecare routine. Even though further validation is needed, counting microvascular lesions in a single retinal field can be proposed as a rapid screening system to classify DR patients with different stages of severity according to the international classification