Neuroimmune response and oxidative stress in the prefrontal cortex mediate seizure susceptibility in experimental colitis in male mice.

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder. Oxidative stress and inflammatory responses have a vital role in the pathophysiology of IBD as well as seizure. IBD is associated with extraintestinal manifestations. This study aimed to explore the relationship between colitis and susceptibility to seizures, with a focus on the roles of neuroinflammation and oxidative stress in acetic acid-induced colitis in mice. Forty male Naval Medical Research Institute mice were divided into four groups: control, colitis, pentylenetetrazole (PTZ), and colitis + PTZ. Colitis was induced by intrarectal administration of acetic acid, and seizures were induced by intravenous injection of PTZ 7 days postcolitis induction. Following the measurement of latency to seizure, the mice were killed, and their colons and prefrontal cortex (PFC) were dissected. Gene expression of inflammatory markers including interleukin-1β, tumor necrosis factor-alpha, NOD-like receptor protein 3, and toll-like receptor 4, as well as total antioxidant capacity (TAC), malondialdehyde (MDA), and nitrite levels were measured in the colon and PFC. Histopathological evaluations were performed on the colon samples. Data were analyzed by t-test or one-way variance analysis. Colitis decreased latency to seizure, increased gene expression of inflammatory markers, and altered levels of MDA, nitrite, and TAC in both the colon and PFC. Simultaneous induction of colitis and seizure exacerbated the neuroimmune response and oxidative stress in the PFC and colon. Results concluded that neuroinflammation and oxidative stress in the PFC at least partially mediate the comorbid decrease in seizure latency in mice with colitis.