19 research outputs found
Reduced Adrenomedullin Parallels Microtubule Dismantlement in Frontotemporal Lobar Degeneration
AR facilitates YAP-TEAD interaction with the AM promoter to enhance mast cell infiltration into cutaneous neurofibroma
Losartan inhibits LPS-induced inflammatory signaling through a PPARÎł-dependent mechanism in human THP-1 macrophages
Degranulation of mast cells induced by gastric cancer-derived adrenomedullin prompts gastric cancer progression
The facilitative glucose transporter GLUT12: what do we know and what would we like to know?
Lack of adrenomedullin in mouse endothelial cells results in defective angiogenesis, enhanced vascular permeability, less metastasis, and more brain damage
Impairment of the Ubiquitin-Proteasome Pathway in RPE Alters the Expression of Inflammation Related Genes
Angiotensin II AT1 Receptor Blockade Ameliorates Brain Inflammation
Brain inflammation has a critical role in the pathophysiology of brain diseases of high prevalence and economic impact, such as major depression, schizophrenia, post-traumatic stress disorder, Parkinson's and Alzheimer's disease, and traumatic brain injury. Our results demonstrate that systemic administration of the centrally acting angiotensin II AT1 receptor blocker (ARB) candesartan to normotensive rats decreases the acute brain inflammatory response to administration of the bacterial endotoxin lipopolysaccharide (LPS), a model of brain inflammation. The broad anti-inflammatory effects of candesartan were seen across the entire inflammatory cascade, including decreased production and release to the circulation of centrally acting proinflammatory cytokines, repression of nuclear transcription factors activation in the brain, reduction of gene expression of brain proinflammatory cytokines, cytokine and prostanoid receptors, adhesion molecules, proinflammatory inducible enzymes, and reduced microglia activation. These effects are widespread, occurring not only in well-known brain target areas for circulating proinflammatory factors and LPS, that is, hypothalamic paraventricular nucleus and the subfornical organ, but also in the prefrontal cortex, hippocampus, and amygdala. Candesartan reduced the associated anorexic effects, and ameliorated associated body weight loss and anxiety. Direct anti-inflammatory effects of candesartan were also documented in cultured rat microglia, cerebellar granule cells, and cerebral microvascular endothelial cells. ARBs are widely used in the treatment of hypertension and stroke, and their anti-inflammatory effects contribute to reduce renal and cardiac failure. Our results indicate that these compounds may offer a novel and safe therapeutic approach for the treatment of brain disorders