No abstract

The piriform cortex makes strong interconnections with limbic structures (amygdala, entorhinal cortex and hippocampus) that are involved in memory processing. These connections have also been implicated in the development of temporal lobe epilepsy. However, little is known about how neurones in this region may change during seizure genesis. Here we tested the hypothesis that in the kindling model of temporal lobe epilepsy GABAA receptor-mediated inhibition is altered in the piriform cortex. To do this we performed whole-cell patch-clamp recordings in piriform cortex brain slices obtained from non-kindled and amygdala-kindled adult rats. We found that kindling coincided with an increase in the amplitude and duration of miniature inhibitory post-synaptic currents (mIPSCs) recorded from non-pyramidal neurones, whereas the mIPSCs occurring on pyramidal (excitatory) cells did not change. Non-stationary noise analysis of mIPSCs occurring on the non-pyramidal neurones showed that inferred unitary conductance of synaptic channels were the same before and after kindling, implying that the channel number increased significantly. Immunocytochemical analysis of the inhibitory innervation showed that it was also unaltered by seizure induction. We also found that the effect of the positive modulator tetrahydrodeoxycorticosterone was reduced on the pyramidal neurones after kindling. In contrast, the potentiating effects of tetrahydrodeoxycorticosterone on non-pyramidal cells were about the same after kindling as in control (sham) rats. These data indicate that amygdala kindling causes a shift in the inhibition 'balance' between the pyramidal and non-pyramidal cells, perhaps leading to the disinhibition of pyramidal cells.

SummaryObjectiveThe ketogenic diet (KD) is a proven treatment for drug‐resistant (DR) seizures in children and adolescents. However, the relationship between seizure control and the most commonly measured metabolite of the diet, the ketone body d‐beta‐hydroxybutyrate (D‐BHB), is controversial. This study was performed to clarify the relationship because specific ketone bodies may be useful as biomarkers of diet efficacy.MethodsFamilies of children with DR seizures were approached for participation in this open‐label, prospective study when they were referred for the KD at two western Canadian children's hospitals. Inclusion criteria included documentation of DR seizures without exclusion based on age, sex, seizure, or syndrome type. Patients were excluded if they were referred for treatment of a metabolic disorder independent of seizures. Seizures were quantified via parental report and standardized as seizure frequency per 28 days. Epilepsy syndromes were identified on the basis of the medical record. Blood D‐BHB was determined by tandem mass spectrometry.ResultsA total of 23 patients were recruited from both sites. Data from five individuals were excluded because these seizures occurred in clusters, leaving 18 patients for the primary analysis. In the latter group, a clear positive correlation was present between measures of seizure frequency and D‐BHB concentrations. However, this failed to reach statistical significance, likely because of the relatively small numbers.SignificanceA trend clearly exists between seizure frequency and D‐BHB levels, so we should not be dissuaded by the lack of statistical significance because it possibly results from methodological techniques, especially sample size. These results call for a larger prospective study in which seizure frequency is assessed at the point of care in a standardized fashion so as to determine whether D‐BHB can be used as a reliable biomarker of KD efficacy.