Manganese nanoparticles induce blood-brain barrier disruption, cerebral blood flow reduction, edema formation and brain pathology associated with cognitive and motor dysfunctions

Nanoparticles affect blood-brain barrier (BBB) and brain edema formation resulting in sensory-motor dysfunction. Exposure of Mn nanoparticles from industrial sources in humans could target basal ganglia resulting in Parkinson's disease. In present investigation, Mn exposure on brain pathology in a rat model was examined. Rats received Mn nanoparticles (30-40nm size) in a dose of 10 or 20mg/kg, i.p. once daily for 7 days and behavioral dysfunctions on Rota Rod performance, inclined plane angle and grid-walking tests as well as gait performances were examined. In addition, BBB breakdown to Evans blue and radioiodine, brain edema formation and neural injuries were also evaluated. Mn nanoparticles treated rats exhibited cognitive and motor dysfunction on the 8th day. At this time, BBB disruption, reduction in cerebral blood flow (CBF), brain edema formation and brain pathology were most marked in the sensory-motor cortex, hippocampus, caudate putamen, cerebellum and thalamus followed by hypothalamus, pons, medulla and spinal cord. In these brain areas, neuronal injuries using Nissl staining was clearly seen. These effects of Mn nanoparticle are dose dependent. These results are the first to demonstrate that Mn nanoparticles induce selective brain pathology resulting in cognitive and motor dysfunction, not reported earlier.