Everolimus in adult tuberous sclerosis complex patients with epilepsy: Too late for success? A retrospective study.

Objective: There is evidence that everolimus (EVE) significantly reduces seizure frequency in epilepsy patients with tuberous sclerosis complex (TSC). Given that TSC-related proliferative processes are more dynamic during brain development, seizure outcomes of patients treated with EVE may be age-related and may be less convincing in adult patients. The aim of this study was to assess the effectiveness and the safety profile of EVE in adults in clinical practice.

First clinical postmarketing experiences in the treatment of epilepsies with brivaracetam: a retrospective observational multicentre study.

Objectives: Brivaracetam (BRV) is the latest approved antiepileptic drug and acts as a synaptic vesicle protein 2A ligand. The aim of the present study was to evaluate the efficacy and tolerability of BRV in the clinical setting.

Design: Retrospective, observational multicentre study.

A deficiency of the link protein Bral2 affects the size of the extracellular space in the thalamus of aged mice.

Bral2 is a link protein stabilizing the binding between lecticans and hyaluronan in perineuronal nets and axonal coats (ACs) in specific brain regions. Using the real-time iontophoretic method and diffusion-weighted magnetic resonance, we determined the extracellular space (ECS) volume fraction (α), tortuosity (λ), and apparent diffusion coefficient of water (ADC ) in the thalamic ventral posteromedial nucleus (VPM) and sensorimotor cortex of young adult (3-6 months) and aged (14-20 months) Bral2-deficient (Bral2 ) mice and age-matched wild-type (wt) controls. The results were correlated with an analysis of extracellular matrix composition.

Altered astrocytic swelling in the cortex of α-syntrophin-negative GFAP/EGFP mice.

Brain edema accompanying ischemic or traumatic brain injuries, originates from a disruption of ionic/neurotransmitter homeostasis that leads to accumulation of K(+) and glutamate in the extracellular space. Their increased uptake, predominantly provided by astrocytes, is associated with water influx via aquaporin-4 (AQP4). As the removal of perivascular AQP4 via the deletion of α-syntrophin was shown to delay edema formation and K(+) clearance, we aimed to elucidate the impact of α-syntrophin knockout on volume changes in individual astrocytes in situ evoked by pathological stimuli using three dimensional confocal morphometry and changes in the extracellular space volume fraction (α) in situ and in vivo in the mouse cortex employing the real-time iontophoretic method.

The impact of alpha-syntrophin deletion on the changes in tissue structure and extracellular diffusion associated with cell swelling under physiological and pathological conditions.

Aquaporin-4 (AQP4) is the primary cellular water channel in the brain and is abundantly expressed by astrocytes along the blood-brain barrier and brain-cerebrospinal fluid interfaces. Water transport via AQP4 contributes to the activity-dependent volume changes of the extracellular space (ECS), which affect extracellular solute concentrations and neuronal excitability. AQP4 is anchored by α-syntrophin (α-syn), the deletion of which leads to reduced AQP4 levels in perivascular and subpial membranes.

The extracellular matrix and diffusion barriers in focal cortical dysplasias.

Focal cortical dysplasias (FCDs) of the brain are recognized as a frequent cause of intractable epilepsy. To contribute to the current understanding of the mechanisms of epileptogenesis in FCD, our study provides evidence that not only cellular alterations and synaptic transmission, but also changed diffusion properties of the extracellular space (ECS), induced by modified extracellular matrix (ECM) composition and astrogliosis, might be involved in the generation or spread of seizures in FCD. The composition of the ECM in FCD and non-malformed cortex (in 163 samples from 62 patients) was analyzed immunohistochemically and correlated with the corresponding ECS diffusion parameter values determined with the real-time iontophoretic method in freshly resected cortex (i.

Bral1: "Superglue" for the extracellular matrix in the brain white matter.

Bral1 is a link protein that stabilizes the binding between lecticans and hyaluronic acid and thus maintains the extracellular matrix assembly in the CNS. Bral1 is specifically located in the white matter around the nodes of Ranvier. Recent studies suggest its function in promoting saltatory neural conduction.

Cell death/proliferation and alterations in glial morphology contribute to changes in diffusivity in the rat hippocampus after hypoxia-ischemia.

To understand the structural alterations that underlie early and late changes in hippocampal diffusivity after hypoxia/ischemia (H/I), the changes in apparent diffusion coefficient of water (ADC(W)) were studied in 8-week-old rats after H/I using diffusion-weighted magnetic resonance imaging (DW-MRI). In the hippocampal CA1 region, ADC(W) analyses were performed during 6 months of reperfusion and compared with alterations in cell number/cell-type composition, glial morphology, and extracellular space (ECS) diffusion parameters obtained by the real-time iontophoretic method. In the early phases of reperfusion (1 to 3 days) neuronal cell death, glial proliferation, and developing gliosis were accompanied by an ADC(W) decrease and tortuosity increase.