Formation of intraneuronal iron deposits following local release from nanostructured silica injected into rat brain parenchyma.

Nanostructured materials with controllable properties have been used to cage and release various types of compounds. In the present study, iron-loaded nanostructured sol-gel SiO-Fe materials were prepared and injected into the rat brain to develop a method for gradual iron delivery into the neurons with the aims to avoid acute iron toxicity and develop an animal model of gradual, metal-induced neurodegeneration. Nanoparticles were prepared by the traditional method of hydrolysis and condensation reactions of tetraethyl orthosilicate at room temperature and subsequent heat treatment at 200 °C. FeSO was added during the silica preparation. The resulting materials were characterized by UV-VIS and infrared spectroscopies, X-ray diffraction, and N adsorption-desorption. An ferrous sulfate release test was carried out in artificial cerebrospinal fluid as the release medium showing successful ferrous sulfate loading on nanostructured silica and sustained iron release during the test time of 10 h. Male Wistar rats administered with SiO-Fe nanoparticles in the () showed significant intraneuronal increase of iron, in contrast to the animals administered with FeSO that showed severe neuronal loss, 72 h post-treatment. Both treatments induced lipid fluorescent product formation in the ventral midbrain, in contrast to iron-free SiO and PBS-only injection controls. Circling behavior was evaluated six days after the intranigral microinjection, considered as a behavioral end-point of brain damage. The apomorphine-induced ipsilateral turns in the treated animals presented significant differences in relation to the control groups, with FeSO administration leading to a dramatic phenotype, compared to a milder impact in SiO-Fe administrated animals. Thus, the use of SiO-Fe nanoparticles represents a slow iron release system useful to model the gradual iron-accumulation process observed in the of patients with idiopathic Parkinson's disease.