Table 1.

Mechanisms of neurotoxicity of titanium dioxide nanoparticles in in vivo studies.

objects	administration route	mechanisms of neurotoxicity	references
rats	intravenous injection	indirect mechanism (induced by cytokines and pro-inflammatory mediators in systemic circulation)	[6]
mice	nasal administration	inflammatory response (over-proliferation in glia cells)	[29]
rats	intravenous injection	OS and angiotensin system	[22]
rats	intravenous injection	multiple (OS, inflammatory response and DNA damage)	[55]
mice	oral administration	OS (ROS and anti-oxidant enzymes disturbed)	[23]
mice	inhalation	OS (H2O2 and MDA elevated)	[24]
mice	oral administration	other mechanisms	[57]
mice	intranasal administration	inflammatory response	[30]
pregnant rats	subcutaneous injection	OS	[26]
pregnant rats	oral administration	other mechanisms (cell proliferation inhibited)	[58]
pregnant mice	subcutaneous injection	other mechanisms (disrupted dopamine systems)	[59–60]
pregnant mice	subcutaneous injection	multiple mechanisms (apoptosis, OS and neurotransmitters)	[50]
mice	nasal instillation	OS	[21]
mice	nasal instillation	multiple mechanisms (OS and inflammatory response)	[49]
mice	delivery in abdominal cavity	OS	[25]
mice	intragastric administration	other mechanisms (disturbed distributions of trace elements, enzymes and neurotransmitters)	[61]
mice	intragastric administration	multiple mechanisms (apoptosis and OS)	[54]
mice	intranasal administration	P38-Nrf-2-mediated OS	[31]
neonatal rats	lactation exposure orally	disturbed synaptic plasticity	[62]
rats	trachea administration	inflammatory response	[32]
mice	injection in abdominal cavity	genotoxicity induced by OS	[43]