MicroPET Outperforms Beta-Microprobes in Determining Neuroreceptor Availability under Pharmacological Restriction for Cold Mass Occupancy.

Both non-invasive micro-positron emission tomography (μPET) and beta-microprobes have the ability to determine radiotracer kinetics and neuroreceptor availability . Beta-microprobes were proposed as a cost-effective alternative to μPET, but literature revealed conflicting results most likely due to methodological differences and inflicted tissue damage. The current study has three main objectives: (i) evaluate the theoretical advantages of beta-microprobes; (ii) perform μPET imaging to assess the impact of (beta-micro)probe implantation on relative tracer delivery (R1) and receptor occupancy (non-displaceable binding potential, BP) in the rat brain; and (iii) investigate whether beta-microprobe recordings produce robust results when a pharmacological restriction for cold mass dose (tracer dose condition) is imposed.

Accelerated high-frequency repetitive transcranial magnetic stimulation enhances motor activity in rats.

High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) is currently accepted as an evidence-based treatment option for treatment-resistant depression (TRD). Additionally, HF-rTMS showed beneficial effects on psychomotor retardation in patients. The classical HF-rTMS paradigms however are unlikely to replace electroconvulsive therapy, a more potent alternative for TRD albeit with important side-effects.

Rat brain normalization templates for robust regional analysis of [11C]ABP688 positron emission tomography/computed tomography.

A methodology to generate rat brain templates for spatial normalization of positron emission tomographic (PET)/computed tomographic (CT) images is described and applied to generate three different templates for imaging of [11C]ABP688, a PET ligand binding to the metabotropic glutamate 5 receptor. The templates are based on functional (PET), structural (CT), and combined PET and CT information, respectively. The templates are created from a test-retest study under normal conditions and are used to assess the different templates by using them in the analysis pipeline of a test-retest and a blocking experiment.

The [18F]FDG μPET readout of a brain activation model to evaluate the metabotropic glutamate receptor 2 positive allosteric modulator JNJ-42153605.

Using [(18)F]fluorodeoxyglucose μ-positron emission tomography ([(18)F]FDG μPET), we compared subanesthetic doses of memantine and ketamine on their potential to induce increases in brain activation. We also studied the reversal effect of the well-known metabotropic glutamate receptor (mGluR)-2/3 agonist LY404039 [(-)-(1R,4S,5S,6S)-4-amino-2-sulfonylbicyclo[3.1.

N-acetylcysteine- and MK-801-induced changes in glutamate levels do not affect in vivo binding of metabotropic glutamate 5 receptor radioligand 11C-ABP688 in rat brain.

Unlabelled: Abnormal glutamate transmission is involved in various neurologic disorders, such as epilepsy, schizophrenia, and Parkinson disease. At present, no imaging techniques are capable of measuring acute fluctuations in endogenous glutamate levels in vivo. We evaluated the potential of (11)C-ABP688, a PET ligand that binds to an allosteric site of the metabotropic glutamate 5 receptor, in rats by using small-animal PET and β-microprobes after pharmacologic challenges with N-acetylcysteine (NAc) and MK-801.

Quantifying the effect of repetitive transcranial magnetic stimulation in the rat brain by μSPECT CBF scans.

Background: Repetitive transcranial magnetic stimulation (rTMS) is used to treat neurological and psychiatric disorders such as depression and addiction amongst others. Neuro-imaging by means of SPECT is a non-invasive manner of evaluating regional cerebral blood flow (rCBF) changes, which are assumed to reflect changes in neural activity.

Objective: rCBF changes induced by rTMS are evaluated by comparing stimulation on/off in different stimulation paradigms using microSPECT of the rat brain.

Automatic detection of epileptic seizures on the intra-cranial electroencephalogram of rats using reservoir computing.

Introduction: In this paper we propose a technique based on reservoir computing (RC) to mark epileptic seizures on the intra-cranial electroencephalogram (EEG) of rats. RC is a recurrent neural networks training technique which has been shown to possess good generalization properties with limited training.

Materials: The system is evaluated on data containing two different seizure types: absence seizures from genetic absence epilepsy rats from Strasbourg (GAERS) and tonic-clonic seizures from kainate-induced temporal-lobe epilepsy rats.

Repeated assessment of larynx compound muscle action potentials using a self-sizing cuff electrode around the vagus nerve in experimental rats.

Rationale: Vagus nerve stimulation (VNS) is an adjunctive treatment for patients with refractory epilepsy. In more than 30% of the patients VNS has no therapeutic effect. The goal of this study was to find an objective parameter that can be used as an indicator of effective stimulation of the vagus nerve.

Increased hippocampal noradrenaline is a biomarker for efficacy of vagus nerve stimulation in a limbic seizure model.

Vagus nerve stimulation (VNS) is an effective adjunctive treatment for medically refractory epilepsy. In this study, we measured VNS-induced changes in hippocampal neurotransmitter levels and determined their potential involvement in the anticonvulsive action of VNS, to elucidate the mechanism of action responsible for the seizure suppressing effect of VNS in an animal model for limbic seizures. We used in vivo intracerebral microdialysis to measure VNS-induced changes in hippocampal extracellular concentrations of noradrenaline, dopamine, serotonin and GABA in freely moving, male Wistar rats.

A novel implantable vagus nerve stimulation system (ADNS-300) for combined stimulation and recording of the vagus nerve: pilot trial at Ghent University Hospital.

Purpose: Vagus nerve stimulation (VNS) is an established treatment for refractory epilepsy. The ADNS-300 is a new system for VNS that includes a rechargeable stimulus generator and an electrode for combined stimulation and recording. In this feasibility study, three patients were implanted with ADNS-300 for therapeutic VNS.

Suppression of hippocampal epileptic seizures in the kainate rat by Poisson distributed stimulation.

Purpose: Hippocampal deep brain stimulation (DBS) is an experimental therapy for patients with pharmacoresistant temporal lobe epilepsy (TLE). Despite the successful clinical application of DBS, the optimal stimulation parameters are undetermined. We evaluate the efficacy of a new form of DBS, using continuous stimuli with Poisson distributed intervals (Poisson distributed stimulation, PDS) in the kainate (KA) rat model, a validated model for human TLE.

Continuous local intrahippocampal delivery of adenosine reduces seizure frequency in rats with spontaneous seizures.

Purpose: Despite different treatment options for patients with refractory epilepsy such as epilepsy surgery and neurostimulation, many patients still have seizures and/or drug-related cerebral and systemic side effects. Local intracerebral delivery of antiepileptic compounds may represent a novel strategy with specific advantages such as the option of higher local doses and reduced side effects. In this study we evaluate the antiepileptic effect of local delivery of adenosine in the kainic acid rat model, a validated model for temporal lobe epilepsy.

Hippocampal deep brain stimulation induces decreased rCBF in the hippocampal formation of the rat.

Deep brain stimulation (DBS) is a promising experimental approach to treat various neurological disorders. However, the optimal stimulation paradigm and the precise mechanism of action of DBS are unknown. Neuro-imaging by means of Single Photon Emission Computed Tomography (SPECT) is a non-invasive manner of evaluating regional cerebral blood flow (rCBF) changes, which are assumed to reflect changes in neural activity.

Comparison of hippocampal Deep Brain Stimulation with high (130Hz) and low frequency (5Hz) on afterdischarges in kindled rats.

Hippocampal Deep Brain Stimulation (DBS) is proposed as an experimental treatment for refractory epilepsy, but the optimal stimulation parameters are undetermined. High frequency hippocampal DBS at 130Hz is effective in both animals and patients with epilepsy. Low frequency stimulation (approximately 5Hz) is assumed to have anti-epileptic properties but the efficacy is highly debated.

Unconditioned adult-derived neurosphere cells mainly differentiate towards astrocytes upon transplantation in sclerotic rat hippocampus.

Purpose: Cell transplantation is being investigated as an alternative treatment for medically refractory temporal lobe epilepsy (TLE). In this study the fate of adult-derived neurosphere cells was evaluated after transplantation in the lesioned hippocampus of the intrahippocampal kainic acid (KA) model for TLE.

Methods: Neurosphere-forming cells were derived from the subventricular zone (SVZ) of transgenic green fluorescent protein (GFP) reporter mice and expanded in culture.

Electrical stimulation for the treatment of epilepsy.

Despite the advent of new pharmacological treatments and the high success rate of many surgical treatments for epilepsy, a substantial number of patients either do not become seizure-free or they experience major adverse events (or both). Neurostimulation-based treatments have gained considerable interest in the last decade. Vagus nerve stimulation (VNS) is an alternative treatment for patients with medically refractory epilepsy, who are unsuitable candidates for conventional epilepsy surgery, or who have had such surgery without optimal outcome.

High frequency deep brain stimulation in the hippocampus modifies seizure characteristics in kindled rats.

Purpose: This experimental animal study evaluates the effect of high frequency deep brain stimulation (HFS DBS) on seizures in the Alternate Day Rapid Kindling model for temporal lobe epilepsy (TLE). The target for HFS is the hippocampus, as this structure is often presumed to be the seizure focus in human TLE.

Methods: Rats (n = 12) were fully kindled in the hippocampus according to the Alternate Day Rapid Kindling protocol.

Neuromodulation with levetiracetam and vagus nerve stimulation in experimental animal models of epilepsy.

Epilepsy is a neurological disorder consisting of recurrent seizures, resulting from excessive, uncontrolled electrical activity in the brain. Epilepsy treatment is successful in the majority of the cases; however; still one third of the epilepsy patients are refractory to treatment. Besides the ongoing research on the efficacy of antiepileptic treatments in suppressing seizures (anti-seizure effect), we want to seek for therapies that can lead to plastic, neuromodulatory changes in the epileptic network.

Rapid kindling in preclinical anti-epileptic drug development: the effect of levetiracetam.

Purpose: This study assesses the use of the serial day Rapid Kindling with Recurrent Hippocampal Seizures (RKRHS) model in drug testing by investigating the anti-epileptic effect of levetiracetam (LEV), a novel anti-epileptic drug (AED) with a unique preclinical profile.

Methods: Male Wistar rats (n=16) were implanted with a stimulation/recording electrode unit in the right hippocampus and epidural recording electrodes. One week later, all rats received 12 stimulations each day for several consecutive days according to the serial day RKRHS protocol, until they were fully kindled.