Global transgenic upregulation of KCC2 confers enhanced diazepam efficacy in treating sustained seizures.

Reduced anticonvulsant efficacy of benzodiazepines is a problem in the treatment of status epilepticus, with up to 50% of patients failing to respond to their first dose. KCC2 is a neuronal K -Cl co-transporter that helps set and maintain intracellular Cl concentrations. KCC2 functional downregulation is a potential contributor to benzodiazepine resistance.

The effect of route of administration on the enantioselective pharmacokinetics of ketamine and norketamine in rats.

Background: Ketamine has been shown to produce a rapid and potent antidepressant response in patients with treatment-resistant depression. Currently ketamine is most commonly administered as a 40-minute intravenous infusion, though it is unknown whether this is the optimal route of administration.

Aims: To determine the plasma concentration time course of the R- and S-enantiomers of ketamine and norketamine following administration of ketamine by four different routes of administration.

Acute low-dose ketamine produces a rapid and robust increase in plasma BDNF without altering brain BDNF concentrations.

Peripheral BDNF changes after ketamine administration have been proposed as a biomarker for brain BDNF changes. However, published data are conflicting and come from studies in paired animal groups. This study determined the time course of plasma BDNF concentrations following the administration of a single 10 mg/kg dose of ketamine by different routes of administration in rats.

Validation of optical voltage reporting by the genetically encoded voltage indicator VSFP-Butterfly from cortical layer 2/3 pyramidal neurons in mouse brain slices.

Understanding how behavior emerges from brain electrical activity is one of the ultimate goals of neuroscience. To achieve this goal we require methods for large-scale recording of the electrical activity of specific neuronal circuits. A very promising approach is to use optical reporting of membrane voltage transients, particularly if the voltage reporter is genetically targeted to specific neuronal populations.

Cardiac electrographic and morphological changes following status epilepticus: effect of clonidine.

Purpose: Status epilepticus has been increasingly associated with cardiac injury in both clinical and animal studies. Our group has previously shown that excitotoxic seizure induction results in the formation of ischaemic myocardial infarcts and loss of cardiac haemodynamic function. We hypothesised that attenuation of cardiac sympathetic/parasympathetic balance with a central presynaptic α₂ agonist, clonidine, can reduce the development of interictal ECG and ventricular morphological changes resulting from kainic acid (KA; 10mg/kg) induced status epilepticus in a conscious rat model.

Pharmacological Preconditioning with GYKI 52466: A Prophylactic Approach to Neuroprotection.

Some toxins and drugs can trigger lasting neuroprotective mechanisms that enable neurons to resist a subsequent severe insult. This "pharmacological preconditioning" has far-reaching implications for conditions in which blood flow to the brain is interrupted. We have previously shown that in vitro preconditioning with the AMPA receptor antagonist GYKI 52466 induces tolerance to kainic acid (KA) toxicity in hippocampus.