Bacterial Lipopolysaccharide Post-Conditioning in The kainic acid animal model of Temporal Lobe epilepsy

Epilepsy Behav. 2024 Oct 27:161:110076. doi: 10.1016/j.yebeh.2024.110076. Online ahead of print.

Abstract

This study used intra-hippocampal injections of Kainic Acid (KA) in Wistar rats to induce spontaneous recurrent seizures (SRS) after a 9-day latent period. A post-conditioning protocol with LPS, injected at the same site 72 h after the initial KA insult, was employed to trigger secondary competing processes. To evaluate the post-conditioning effect of LPS, 25 animals were divided into four groups: SAL-SAL (n = 6), KA-SAL (n = 6), SAL-LPS (n = 7), and KA-LPS (n = 6). SRS occurrence and seizure duration were quantified through video monitoring from days 9 to 17, along with other ictal behaviors, such as tail-chasing and wet-dog-shakes. Behavioral assessments revealed that the KA-LPS group had preserved sucrose preference and intact long-term memory in the object recognition test, indicating reduced depressive-like behavior and cognitive preservation compared to the KA-SAL group. The forced swim test showed increased depressive-like behavior in the SAL-LPS group, with LPS mitigating these effects in the KA group. The marble-burying test showed no significant differences among groups. Animals were euthanized on day 26, and hippocampal slices were analyzed using fluoro-jade staining for cell death and immunofluorescence staining for Iba-1 (microglia) and GFAP (astrocyte) labeling. The results support the hypothesis that epileptogenesis involves a cascade of plastic changes in neural networks and that precise, timely interventions can potentially interfere with this process.

Keywords: Competing circuits; Epilepsy; Epileptogenesis; Kainic Acid; LPS; Network; Plasticity; Post-conditioning.