Diabetes Aggravates Nanoparticles Induced Breakdown of the Blood-Brain Barrier Permeability, Brain Edema Formation, Alterations in Cerebral Blood Flow and Neuronal Injury. An Experimental Study Using Physiological and Morphological Investigations

摘要

The possibility that diabetes aggravates nanoparticles induced blood-brain barrier (BBB) break-down, edema formation and brain pathology was examined in a rat model. Engineered nanoparticles from metals Ag and Cu (50-60 mn) were administered (50 mg/kg, i.p.) once daily for 7 days in normal and streptozotocine induced diabetic rats. On the 8th day, BBB permeability to Evans blue and radioactive iodine (~(131)I-sodium) was examined in 16 brain regions. In these brain regions alterations in regional CBF was also evaluated using radiolabelled (~(125)I) carbonized microspheres (o.d. 15±6 μm). Regional brain edema and Na~+, K~+ and Cl~- ion analysis were done in 8 selected brain regions. Histopathology was used to detect neuronal damage employing Nissl staining. Nanoparticles treatment in diabetic rats showed much more profound disruption of the BBB to Evans blue albumin (EBA) and radioiodine in almost all the 16 regions examined as compared to the normal animals. In these diabetic animals reduction in regional cerebral blood flow (CBF) was more pronounced than in normal rats. Edema development as seen using water content and increase in Na~+ and a decrease in K~+ ion were most marked in diabetic rats as compared to normal rats after nanoparticles treatment. Cell changes in the regions of BBB disruptions were also exacerbated in diabetic rats compared to normal group after nanoparticles treatment. Taken together, these observations are the first to show that diabetic rats are more susceptible to nanoparticles induced cerebrovascular reactions in the brain and neuronal damage. The possible mechanisms and significance of the present findings are discussed.