Exposure to carbon black nanoparticles increases seizure susceptibility in male mice

Abstract

Carbon black nanoparticles (CBNPs) can enter the central nervous system through blood circulation and olfactory nerves, affecting brain development or increasing neurological disease susceptibility. However, whether CBNPs exposure affects seizure is unclear. Herein, mice were exposed to two different doses of CBNPs (21 and 103 μg/animal) based on previous studies and the maximum exposure limitation (4 mg/m³) in occupational workplaces set by the Chinese government. In the pentylenetetrazol (PTZ) and kainic acid (KA) seizure models, high-dose CBNPs exposure increased seizure susceptibility in both models and increased spontaneous recurrent seizure (SRS) frequency in the KA model. In vivo local field potential (LFP) recording in KA model mice revealed that both low-dose and high-dose CBNPs exposure increased seizure-like event (SLE) frequency in the SRS interval but shortened SLE duration. Intriguingly, H&E staining and Nissl staining on brain tissue revealed that CBNPs exposure did not cause significant brain tissue morphology or neuronal damage. Detection of inflammatory factors, such as TNF-α, TGF-β1, IL-1β, and IL-6, in brain tissue showed that only high dose of CBNPs exposure increased the expression of cortical TGF-β1. By using the primary cultured neurons, we observed that CBNPs exposure not only significantly decreased the expression of the neuronal marker MAP2 but also enhanced the levels of action potential frequency in the neurons. In general, CBNPs exposure can affect abnormal epileptic discharges during the seizure interval and enhance susceptibility to frequent seizures. Our findings suggest that minimizing CBNPs exposure may be a potential way to prevent or ease seizure.

Keywords:

• Carbon black nanoparticles
• epilepsy
• seizure susceptibility
• field potential

Author contributions

MH, ZZ, and CC performed the CBNPs exposure experiments; MH and XJ performed the behavioral experiments in PTZ and KA seizure models; MH, XT, and ZZ performed the experiments in the LFP recording; SZ, XJ, and XQ performed the ELISA and staining experiments; YG performed the cell patch clamp experiments; SZ and CC performed the immunofluorescence experiments; XW, XT, and CC designed the experiment and supervised the experimental process; MH, XT, and CC analyzed the experimental data and wrote the manuscript. All authors revised and approved the final version of the manuscript.

Disclosure statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Additional information

Funding

This research was partially supported by National Natural Science Foundation of China [81602820, 81703187, 81903358]; Foundation and Frontier Research Program of Chongqing Municipal Science and Technology Commission [cstc2017jcyjAX0162]; China Postdoctoral Science Foundation funded project [2017M612925 and 2018T110951]; Science and Technology Research Program of Chongqing Education Commission [KJQN201800434 and KJQN201900419]; Commission of Science and Technology of Yuzhong district of Chongqing [20160101]. Cultivating Fund of the First Affiliated Hospital of Chongqing Medical University [PYJJ2019-201].