Time-dependent translocation of titanium dioxide nanoparticles to the brain: A histopathological and spectrometric study.

UNLABELLED: The surface of titanium (Ti)-based biomedical devices is a potential endogenous source of systemic exposure to titanium dioxide nanoparticles (TiO₂-NPs). Experimental evidence indicates that TiO₂-NPs can disseminate systemically and reach distant organs, including the brain; however, their long-term neurobiological effects in vivo remain poorly characterized. However, their long-term neurobiological effects remain poorly characterized and need to be further investigated in in vivo studies. The aim of this study was to evaluate the presence and temporal distribution of 5 nm TiO₂-NP deposits in the brain and histopathological changes associated with the observed deposits, and Ti levels in brain and plasma using an experimental rat model of acute (1 month) and chronic (6 and 12 months) exposure to TiNPs.

METHODS

Male Wistar rats (n = 48) were intraperitoneally injected with 5 nm TiO₂-NPs or saline solution. One, six, and 12 months post-injection, the presence of titanium particles was evaluated histologically and by scanning electron microscopy (SEM) coupled with energy-dispersive X-ray spectrometry (SEM-EDS), the occurrence of particle-associated alterations was analyzed histopathologically, and Ti concentration in brain and plasma was quantified by inductively coupled plasma-mass spectrometry (ICP-MS). Results were statistically analyzed using two-way ANOVA followed by Bonferroni post -hoc tests.

RESULTS

Histopathological analysis revealed gliosis, neuronal satellitosis, and deposits of particle-like material in the brain of exposed animals at all the time points, with no evidence of inflammatory infiltration. SEM-EDS confirmed the presence of Ti-containing particles in brain tissue. Ti concentration in both brain and plasma was significantly higher in the TiO₂-NP5 group compared with controls at all the studied times points (p < 0.05) and increased gradually with time, showing a significant rise at 12 months.

CONCLUSIONS

These findings demonstrate that 5 nm TiO₂-NPs can cross the blood-brain barrier after both acute and chronic exposure and deposit in brain tissue over time. Although no inflammatory response was observed under the experimental conditions used here, the progressive accumulation of Ti highlights the need for further studies addressing the molecular and functional consequences of long-term exposure to nanoparticles.