Subacute exposure of rats by metal oxide nanoparticles through the airways: general toxicity and neuro-functional effects

In order to create an animal model of human inhalational exposure by industrial trAct metal fumes, nanoparticulate metal oxides (MnO2 , CdO2 , PbO) were synthesized and instilled into the trachea of rats 5 times a week for 6 weeks (metal doses per kg b.w.: 2.63 and 5.26 mg Mn; 0.04 and 0.4 mg Cd; 2 and 4 mg Pb). At the end, the rats’ body weight gain during the treatment was determined, the animals had an open field session to investigate their spontaneous motility, and finally spontaneous and stimulus-evoked cortical activity was recorded in urethane anaesthesia. Mn caused decrease of open field ambulation and rearing, Cd had no effect, whereas Pb caused decreased rearing and increased ambulation. Spontaneous cortical activity was shifted to higher frequencies with each metal. Cortical evoked potentials had lengthened latency, mainly with Mn and Cd; and increased frequency dependence with Cd and Pb but hardly with Mn. The effects proved indirectly that the metal content of the nanoparticles had access form the airways to the CNS. Our method seems suitable for modelling human nervous system damage due to inhaled nanoparticles

Repeated simultaneous cortical electrophysiological and behavioral recording in rats exposed to manganese-containing nanoparticles

Male Wistar rats wearing chronically implanted cortical electrodes were exposed to Mn-containing nanoparticles via the airways for 8 weeks following a 2-week pre-exposure period. The rats’ cortical electrical activity and open field motility was recorded simultaneously, in weekly repetitions. It was supposed that this technique can provide better insight in the development of Mn-induced CNS damage. Decreased motility (less distance covered, longer periods of immobility) and increased total power of cortical electrical activity developed in parallel in the first 4–5 weeks of treatment but showed little change afterwards. Both the behavioral and the electrophysiological effect were in fair correlation with the rats’ internal Mn exposure determined from brain samples. The results confirmed the non-linear dose- and time-dependence of Mn effects suggested by previous studies. Repeated simultaneous behavioral and electrophysiological recording during a longer treatment with neurotoxic metals (or other xenobiotics) seems to be a promising method