Behavioural and Histological Effects of Preconditioning with Lipopolysaccharide in Epileptic Rats

Abstract

Sublethal stress stimuli such as systemic endotoxin treatment can induce tolerance of the brain to subsequent ischemic stress, which results in a decreased infarct size. Based on this evidence, we hypothesized that lipopolysaccharide (LPS)-induced preconditioning could protect hippocampal neurons in epileptic rats. To test this hypothesis, the anticonvulsant effect of a low dose of LPS against seizures elicited by pilocarpine hydrochloride was measured. Using the pilocarpine model of temporal lobe epilepsy and LPS-preconditioning, we also investigated hippocampal pathology in the rat brain. Based on the behavioural observations conducted, it can be assumed that the preconditioning procedure used may decrease seizure excitability in epileptic rats. However, determination of the seizure excitability threshold needs to be elaborated. Qualitative and quantitative analyses of histological brain sections in the LPS-preconditioned rats showed markedly decreased intensity of neurodegenerative changes in the CA1, CA3 and DG hippocampal fields. The tendency was observed in all the periods of the pilocarpine model of epilepsy. We suggest that preconditioning with LPS may have neuroprotective effects in the CA1, CA3 and DG hippocampal sectors; however, it has no influence on the course of the seizures in rats in the pilocarpine model of epilepsy.

A Functional Role for Microglia in Epilepsy

“…Furthermore, we observed a trend toward reduced seizure activity in LPS preconditioned mice, similarly to what other groups have reported (Sayyah et al, 2003, Akarsu et al, 2006, Arican et al, 2006, Dmowska et al, 2010. These data would suggest that LPS activated microglia were providing some protection to the hippocampus, perhaps by controlling the spread of seizure activity.…”

“…There are a few examples in the literature where preconditioning microglia with LPS modulates seizures including our own, and this will be discussed in more detail in the next section (Sayyah et al, 2003, Akarsu et al, 2006, Arican et al, 2006, Dmowska et al, 2010, Mirrione et al, 2010, Yang et al, 2010a. One mechanism that may contribute to the positive effects attributed to LPS preconditioning is through enhanced neurotrophin release (Nakajima et al, 2001a).…”

“…In kindling, LPS was inhibitory but only when it was administered daily for 16 days, as it blunted the acquisition of kindled behavioral seizures (Sayyah et al, 2003). Neuronal protection from cell death in hippocampal CA1, CA3 and DG was observed with LPS preconditioning 72 hours prior to seizure induction, although seizure behavior was not affected at this low dose of LPS (Dmowska et al, 2010). Importantly, one study addressed the time course of LPS delivery prior to seizure induction and demonstrated complex effects (Akarsu et al, 2006).…”

Various ketogenic diets can differently support brain resistance against experimentally evoked seizures and seizure-induced elemental anomalies of hippocampal formation

“…Moreover, taking into account the elemental data obtained for normal and seizure experiencing rats on ketogenic and standard diets it can be presumed that this effect results from KD2 diet preconditioning action on nerve tissue, protecting in turn the brain from seizure propagation and subsequent damages. A similar phenomenon was observed following ischemia [46] or seizures [47] both preceded by slight inflammation. Most likely, within the thirty days period of the dietary treatment, an internal rearrangement in the hippocampal formation occurred and resulted in the observed changes of its elemental content.…”

Prevention or Modification of Epileptogenesis after Brain Insults: Experimental Approaches and Translational Research

“…Pilocarpine and SE itself are also known to induce neuroinflammatory responses (Voutsinos-Porche et al, 2004;Vezzani and Granata, 2005;Marchi et al, 2007), but the adaptive immune response to lithium clearly differentiates the lithium-pilocarpine model from all other SE models. However, with respect to the effects of inflammation on SE, it is also important to note that administration of the proinflammatory bacterial endotoxin lipopolysaccharide 72 h before pilocarpine did not potentiate its convulsant activity (Dmowska et al, 2010).…”