Chronic treatment with nanoparticles exacerbate hyperthermia induced blood-brain barrier breakdown, cognitive dysfunction and brain pathology in the rat. Neuroprotective effects of nanowired-antioxidant compound H-290/51.

The possibility that chronic exposure of nanoparticles may alter stress reaction and brain pathology following hyperthermia was examined in a rat model. Engineered nanoparticles from Ag or Cu (approximately equal to 50-60 nm) were administered (30 mg/kg, i.p.) once daily for 1 week in young male rats. On the 8th day these animals were subjected to 4 h heat stress at 38 degrees C in a BOD incubator. In these animals stress symptoms, blood-brain barrier (BBB) permeability, cognitive and motor functions and brain pathology were examined. Subjection of nanoparticle treated rats to heat stress showed exacerbation of stress symptoms i.e., hyperthermia, salivation and prostration and exhibited greater BBB disruption, brain edema formation, impairment of cognitive and motor functions and brain damage compared to normal animals. This enhanced brain pathology in heat stress was most marked in animals that received Ag nanoparticles compared to Cu treatment. Treatment with antioxidant compound H-290/51 either 30 min or 60 min after heat stress did not alter hyperthermia induce brain pathology in nanoparticle treated rats. Whereas, administration of nanowired-H-290/51 after 30 min or 60 min heat stress markedly attenuated BBB disruption, sensory motor function and brain pathology. These results suggest that chronic nanoparticles treatment exacerbate hyperthermia induced brain pathology that is significantly attenuated by nanowired but not normal H-290/51 compound. Taken together, our observations suggest that nano-wired drug delivery of H-290/51 is a promising approach to induce neuroprotection in hyperthermia induced brain pathology, not reported earlier.