Transient Seizure Clusters and Epileptiform Activity Following Widespread Bilateral Hippocampal Interneuron Ablation.

Interneuron loss is a prominent feature of temporal lobe epilepsy in both animals and humans and is hypothesized to be critical for epileptogenesis. As loss occurs concurrently with numerous other potentially proepileptogenic changes, however, the impact of interneuron loss in isolation remains unclear. For the present study, we developed an intersectional genetic approach to induce bilateral diphtheria toxin-mediated deletion of Vgat-expressing interneurons from dorsal and ventral hippocampus. In a separate group of mice, the same population was targeted for transient neuronal silencing with DREADDs. Interneuron ablation produced dramatic seizure clusters and persistent epileptiform activity. Surprisingly, after 1 week seizure activity declined precipitously and persistent epileptiform activity disappeared. Occasional seizures (≈1/day) persisted to the end of the experiment at 4 weeks. In contrast to the dramatic impact of interneuron ablation, transient silencing produced large numbers of interictal spikes, a significant but modest increase in seizure occurrence and changes in EEG frequency band power. Taken together, findings suggest that the hippocampus regains relative homeostasis-with occasional breakthrough seizures-in the face of an extensive and abrupt loss of interneurons.

Complex Morphologic Analysis of Cerebral Aneurysms Through the Novel Use of Fractal Dimension as a Predictor of Rupture Status: A Proof of Concept Study.

BACKGROUND: Aneurysm morphology has been correlated with rupture. Previous reports identified several morphologic indices that predict rupture status, but they measure only specific qualities of the morphology of an aneurysm in a semiquantitative fashion. Fractal analysis is a geometric technique whereby the overall complexity of a shape is quantified through the calculation of a fractal dimension (FD). By progressively altering the scale of measurement of a shape and determining the number of segments required to incorporate the entire shape, a noninteger value for the dimension of the shape is derived. We present a proof-of-concept study to calculate the FD of an aneurysm for a small cohort of patients with aneurysms in 2 specific locations to determine whether FD is associated with aneurysm rupture status. METHODS: Twenty-nine aneurysms of the posterior communicating and middle cerebral arteries were segmented from computed tomography angiograms in 29 patients. FD was calculated using a standard box-counting algorithm extended for use with three-dimensional shapes. Nonsphericity index and undulation index (UI) were used to validate the data against previously reported parameters associated with rupture status. RESULTS: Nineteen ruptured and 10 unruptured aneurysms were analyzed. Through logistic regression analysis, lower FD was found to be significantly associated with rupture status (P = 0.035; odds ratio, 0.64; 95% confidence interval, 0.42-0.97 per FD increment of 0.05). CONCLUSIONS: In this proof-of-concept study, we present a novel approach to quantify the geometric complexity of intracranial aneurysms through FD. These data suggest an association between FD and patient-specific aneurysm rupture status.

Hippocampal interneurons are direct targets for circulating glucocorticoids.

The hippocampus has become a significant target of stress research in recent years because of its role in cognitive functioning, neuropathology, and regulation of the hypothalamic-pituitary-adrenal (HPA) axis. Despite the pervasive impact of stress on psychiatric and neurological disease, many of the circuit- and cell-dependent mechanisms giving rise to the limbic regulation of the stress response remain unknown. Hippocampal excitatory neurons generally express high levels of glucocorticoid receptors (GRs) and are therefore positioned to respond directly to serum glucocorticoids. These neurons are, in turn, regulated by neighboring interneurons, subtypes of which have been shown to respond to stress exposure. However, GR expression among hippocampal interneurons is not well characterized. To determine whether key interneuron populations are direct targets for glucocorticoid action, we used two transgenic mouse lines to label parvalbumin-positive (PV+) and somatostatin-positive (SST+) interneurons. GR immunostaining of labeled interneurons was characterized within the dorsal and ventral dentate hilus, dentate cell body layer, and CA1 and CA3 stratum oriens and stratum pyramidale. While nearly all hippocampal SST+ interneurons expressed GR across all regions, GR labeling of PV+ interneurons showed considerable subregion variability. The percentage of PV+, GR+ cells was highest in the CA3 stratum pyramidale and lowest in the CA1 stratum oriens, with other regions showing intermediate levels of expression. Together, these findings indicate that, under baseline conditions, hippocampal SST+ interneurons are a ubiquitous glucocorticoid target, while only distinct populations of PV+ interneurons are direct targets. This anatomical diversity suggests functional differences in the regulation of stress-dependent hippocampal responses.