Effects of Sodium Nitroprusside on Lipopolysaccharide-Induced Inflammation and Disruption of Blood-Brain Barrier.

In various neurodegenerative conditions, inflammation plays a significant role in disrupting the blood-brain barrier (BBB), contributing to disease progression. Nitric oxide (NO) emerges as a central regulator of vascular function, with a dual role in inflammation, acting as both a pro- and anti-inflammatory molecule. This study investigates the effects of the NO donor sodium nitroprusside (SNP) in protecting the BBB from lipopolysaccharide (LPS)-induced inflammation, using bEnd.3 endothelial cells as a model system. Additionally, Raw 264.7 macrophages were employed to assess the effects of LPS and SNP on their adhesion to a bEnd.3 cell monolayer. Our results show that LPS treatment induces oxidative stress, activates the JAK2/STAT3 pathway, and increases pro-inflammatory markers. SNP administration effectively mitigates ROS production and IL-6 expression, suggesting a potential anti-inflammatory role. However, SNP did not significantly alter the adhesion of Raw 264.7 cells to bEnd.3 cells induced by LPS, probably because it did not have any effect on ICAM-1 expression, although it reduced VCAM expression. Moreover, SNP did not prevent BBB disruption. This research provides new insights into the role of NO in BBB disruption induced by inflammation.

Synthesis and Vasorelaxant Activity of Nitrate-Coumarin Derivatives.

Due to the need for new chemical entities for cardiovascular diseases, we have synthesized a new series of nitrate-coumarins and evaluated their vasorelaxant activity in contraction-relaxation studies using rat aorta rings precontracted with phenylephrine or by depolarization with a high concentration of potassium chloride. Four of the new compounds were able to relax smooth vascular muscle with a similar profile and potency to glyceryl trinitrate (IC50 =12.73 nM) and sodium nitroprusside (IC50 =4.32 nM). Coumarin-7-yl-methyl nitrate (4), the best compound within the series, was able to relax smooth vascular muscle in the low nanomolar range (IC50 =1.92 nM). The mechanisms of action have been explored, being the activation of sGC and the opening of K+ channels involved. Our studies indicate that the new nitrate derivatives are reversible and not deleterious for aortic rings, suggesting that these compounds have a potential interest for the development of new and highly efficient vasodilator drugs.

The Gut Microbiota-Brain Axis: A New Frontier on Neuropsychiatric Disorders.

Alzheimer's disease (AD) is a progressive and incurable neurodegenerative disorder of integrative areas of the brain, characterized by cognitive decline and disability resulting in negative impacts on the family of the patients and the health care services worldwide. AD involves oxidative stress, neuroinflammation and accelerated apoptosis, accompanied by deposition of amyloid-ß peptide plaques and tau protein-based neurofibrillary tangles in the central nervous system. Among the multiple factors that contribute to the onset and evolution of this disease, aging stands out. That is why the prevalence of this disease has increased due to the constant increase in life expectancy. In the hope of finding new, more effective methods to slow the progression of this disease, over the last two decades, researchers have promoted "omics"-based approaches that include the gut microbiota and their reciprocal interactions with different targets in the body. This scientific advance has also led to a better understanding of brain compartments and the mechanisms that affect the integrity of the blood-brain barrier. This review aims to discuss recent advances related to the gut-brain-microbiota axis in AD. Furthermore, considering that AD involves psychiatric symptoms, this review also focuses on the psychiatric factors that interact with this axis (an issue that has not yet been sufficiently addressed in the literature).