Shape effect of cerium oxide nanoparticles on mild traumatic brain injury

Abstract

The catalytic performance and therapeutic effect of nanoparticles varies with shape. Here, we investigated and compared the therapeutic outcomes of ceria nanospheres (Ceria NSs) and ceria nanorods (Ceria NRs) in an in vivo study of mild traumatic brain injury (mTBI). In vivo TBI was induced in a mouse model of open head injury using a stereotaxic impactor. Outcomes including cytoprotective effects, cognitive function, and cerebral edema were investigated after retro-orbital injection of 11.6 mM of ceria nanoparticles. Ceria nanoparticles significantly reduced fluoro-jade B (FJB)-positive cells and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells, and restored mRNA levels of superoxide dismutase 1 (SOD1) and SOD2. They also decreased the cyclooxygenase-2 (COX-2) expression compared with the untreated control group. Comparing the two nanomaterials, Ceria NRs showed less stable and high-energy (100) and (110) planes, which increased the number of active sites. The Ce3+/Ce4+ molar ratio of Ceria NRs (0.40) was greater than that of Ceria NSs (0.27). Ceria NRs (0.059 ± 0.021) appeared to exhibit better anti-inflammatory effect than Ceria NSs (0.133 ± 0.024), but the effect was statistically insignificant (p = 0.190). Ceria nanoparticles also improved cognitive impairment following mTBI compared with the control group, but the effect did not differ significantly according to the nanoshape. However, Ceria NRs (70.1 ± 0.5%) significantly decreased brain water content compared with Ceria NSs (73.7 ± 0.4%; p = 0.0015), indicating a more effective reduction in brain edema (p = 0.0015). Compared with Ceria NSs, the Ceria NRs are more effective in alleviating cerebral edema following in vivo mTBI.

Morphology‐controlled therapeutic activity of cerium oxide nanoparticles for mild traumatic brain injury

“…In CeO x NRs, (1 0 0) and (1 1 0) planes are predominately exposed. 5 For particles with the size of 3-10 nm, CeO x NPs predominantly have truncated octahedral morphology with (1 0 0) and (1 1 1) facets. 38 CeO x NCs have six (1 0 0) faces.…”

“…24 The (1 0 0) and (1 1 0) facets provide more active sites than (1 1 1) because of their lower stability and higher energy; therefore, the biomedical activity of nanocrystals with exposed (1 0 0) and (1 1 0) planes is better than that of the crystal with (1 1 1) exposed crystal plane. 5 Accordingly, CeO x NRs and CeO x NCs can show better biomedical performance than CeO x NPs. Second, the Ce 3+ /Ce 4+ molar ratio on the cerium oxide surfaces plays an essential role in bioactivity.…”

“…24 Previously, we reported that cerium oxide nanorods (CeO x NRs) were more effective in reducing cerebral edema than cerium oxide nanospheres (CeO x NSs) in in vivo mild TBI. 5 In addition, CeO x NRs showed better antiinflammatory effect than CeO x NSs in in vivo TBI. 25 In-line with these studies, we tested the ability of CeO x NRs with two different aspect ratios to reduce neuroinflammation and oxidative stress, and alleviate cognitive impairment after mild TBI in in vivo and in vitro models.…”

Mild Traumatic Brain Injury and Subsequent Acute Pulmonary Inflammatory Response

“…However, in general, the absence of intracranial hemorrhage is often called mild TBI in clinical practice. Thus, our results may reflect a slightly more severe form than actual clinically mild TBI, although we performed a well-established and commonly used mild TBI model [ 19 ]. Third, several factors such as the anesthetic agent and microaspiration might influence the experimental results.…”

The Therapeutic Role of Nanoparticle Shape in Traumatic Brain Injury : An in vitro Comparative Study

“…The mixture was naturally cooled to ambient temperature, and Ceria NSs were precipitated by adding ethanol (75 mL). The obtained product was collected by centrifugation and washed repeatedly with ethanol, and then dried under vacuum for 24 hours for further use [ 20 ].…”