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.