Species-specific neuronal localization of kynurenine aminotransferase-2 in the mouse cerebellum.

The immunohistochemical pattern of kynurenine aminotransferase-2 (KAT-2) - the key role enzyme in the production of neuroactive and neuroprotective kynurenic acid (KYNA) - was studied in the cerebellum of mice. It is known from literature that KAT-2 is localized mainly in astrocytes in different parts of the cerebrum. Kynurenine aminotransferase (KAT) activity in the cerebellum is relatively low and alternative production routes for KYNA have been described there.

Investigating KYNA production and kynurenergic manipulation on acute mouse brain slice preparations.

Manipulation of kynurenic acid (KYNA) level through kynurenine aminotransferase-2 (KAT-2) inhibition with the aim of therapy in neuro-psychiatric diseses has been the subject of extensive recent research. Although mouse models are of particular importance, neither the basic mechanism of KYNA production and release nor the relevance of KAT-2 in the mouse brain has yet been clarified. Using acute mouse brain slice preparations, we investigated the basal and L-kynurenine (L-KYN) induced KYNA production and distribution between the extracellular and intracellular compartments.

Systemic administration of l-kynurenine sulfate induces cerebral hypoperfusion transients in adult C57Bl/6 mice.

The kynurenine pathway is a cascade of enzymatic steps generating biologically active compounds. l-kynurenine (l-KYN) is a central metabolite of tryptophan degradation. In the mammalian brain, l-KYN is partly converted to kynurenic acid (KYNA), which exerts multiple effects on neurotransmission.

Astrocytic and neuronal localization of kynurenine aminotransferase-2 in the adult mouse brain.

During catabolism of tryptophan through the kynurenine (KYN) pathway, several endogenous metabolites with neuromodulatory properties are produced, of which kynurenic acid (KYNA) is one of the highest significance. The causal role of altered KYNA production has been described in several neurodegenerative and neuropsychiatric disorders (e.g.

Acetyl-l-carnitine restores synaptic transmission and enhances the inducibility of stable LTP after oxygen-glucose deprivation.

Hypoxic circumstances result in functional and structural impairments of the brain. Oxygen-glucose deprivation (OGD) on hippocampal slices is a technique widely used to investigate the consequences of ischemic stroke and the potential neuroprotective effects of different drugs. Acetyl-l-carnitine (ALC) is a naturally occurring substance in the body, and it can therefore be administered safely even in relatively high doses.

Real-time dynamic calibration of a tunable frequency laser source using a Fabry-Pérot interferometer.

We report on a method for real-time dynamic calibration of a tunable external cavity diode laser by using a partially mode-matched plano-concave Fabry-Pérot interferometer in reflection geometry. Wide range laser frequency scanning is carried out by piezo-driven tilting of a diffractive grating playing the role of a frequency selective mirror in the laser cavity. The grating tilting system has a considerable mechanical inertness, so static laser frequency calibration leads to false results.

Systemic L-Kynurenine sulfate administration disrupts object recognition memory, alters open field behavior and decreases c-Fos immunopositivity in C57Bl/6 mice.

L-Kynurenine (L-KYN) is a central metabolite of tryptophan degradation through the kynurenine pathway (KP). The systemic administration of L-KYN sulfate (L-KYNs) leads to a rapid elevation of the neuroactive KP metabolite kynurenic acid (KYNA). An elevated level of KYNA may have multiple effects on the synaptic transmission, resulting in complex behavioral changes, such as hypoactivity or spatial working memory deficits.

Unexpected effects of peripherally administered kynurenic acid on cortical spreading depression and related blood-brain barrier permeability.

Cortical spreading depression (CSD) involves a slowly-propagating depolarization wave in the cortex, which can appear in numerous pathophysiological conditions, such as migraine with aura, stroke, and traumatic brain injury. Neurons and glial cells are also depolarized transiently during the phenomena. CSD is followed by a massive increase in glutamate release and by changes in the brain microcirculation.

A simple novel technique to induce short-lasting local brain ischaemia in the rat.

Aims: Brain ischaemia models are essential to study the pathomechanisms of stroke. Our aim was to investigate the reliability and reproducibility of our novel focal ischaemia-reperfusion model.

Methods: To induce a cortical transient ischaemic attack, we lifted the distal middle cerebral artery (MCA) with a special hook.

Behavioural studies with a newly developed neuroprotective KYNA-amide.

The neuroactive properties and neuroprotective potential of endogenous L: -kynurenine, kynurenic acid (KYNA) and its derivatives are well established. KYNA acts as an antagonist on the obligatory co-agonist glycine site, and has long been at the focus of neuroprotective trials. Unfortunately, KYNA is barely able to cross the blood-brain barrier.

Kainate postconditioning restores LTP in ischemic hippocampal CA1: onset-dependent second pathophysiological stress.

Postconditioning can be induced by a broad range of stimuli within minutes to days after an ischemic cerebral insult. A special form is elicited by pharmacological intervention called second pathophysiological stress. The present study aimed to evaluate the effects of low-dose (5 mg/kg) kainate postconditioning with onsets 0, 24 and 48 h after the ischemic insult on the hippocampal synaptic plasticity in a 2-vessel occlusion model in rat.

Neuroprotection with a new kynurenic acid analog in the four-vessel occlusion model of ischemia.

Global forebrain ischemia results in damage to the pyramids in the CA1 hippocampal subfield, which is particularly vulnerable to excitotoxic processes. Morphological and functional disintegration of this area leads to a cognitive dysfunction and neuropsychiatric disorders. Treatment with N-methyl-d-aspartate receptor antagonists is a widely accepted method with which to stop the advance of excitotoxic processes and concomitant neuronal death.

Effects of blood glutamate scavenging on cortical evoked potentials.

It is well known that traumatic or ischemic brain injury is followed by acute excitotoxicity caused by the presence of abnormally high glutamate (Glu) in brain fluids. It has recently been demonstrated that excess Glu can be eliminated from brain into blood following the intravenous administration of oxaloacetate (OxAc), which, by scavenging blood Glu, induces an enhanced and neuroprotective brain-to-blood Glu efflux. In this study, we subjected rats to intravenous OxAc administration (i.

A novel kynurenic acid analogue: a comparison with kynurenic acid. An in vitro electrophysiological study.

Kynurenic acid is an endogenous product of the tryptophan metabolism, and as a broad-spectrum antagonist of excitatory amino acid receptors may serve as a protective agent in neurological disorders. The use of kynurenic acid as a neuroprotective agent is rather limited, however, because it has only restricted ability to cross the blood-brain barrier. Accordingly, new kynurenic acid analogues which can readily cross the blood-brain barrier and exert their complex anti-excitotoxic activity are greatly needed.

Oxaloacetate decreases the infarct size and attenuates the reduction in evoked responses after photothrombotic focal ischemia in the rat cortex.

A traumatic brain injury or a focal brain lesion is followed by acute excitotoxicity caused by the presence of abnormally high glutamate (Glu) levels in the cerebrospinal and interstitial fluids. It has recently been demonstrated that this excess Glu in the brain can be eliminated into the blood following the intravenous administration of oxaloacetate (OxAc), which, by scavenging the blood Glu, induces an enhanced and neuroprotective brain-to-blood Glu efflux. In this study, we subjected rats to a photothrombotic lesion and treated them after the illumination with a single 30-min-long administration of OxAc (1.

Oxaloacetate restores the long-term potentiation impaired in rat hippocampus CA1 region by 2-vessel occlusion.

Various acute brain pathological conditions are characterized by the presence of elevated glutamate concentrations in the brain interstitial fluids. It has been established that a decrease in the blood glutamate level enhances the brain-to-blood efflux of glutamate, removal of which from the brain may prevent glutamate excitotoxicity and its contribution to the long-lasting neurological deficits seen in stroke. A decrease in blood glutamate level can be achieved by exploiting the glutamate-scavenging properties of the blood-resident enzyme glutamate-oxaloacetate transaminase, which transforms glutamate into 2-ketoglutarate in the presence of the glutamate co-substrate oxaloacetate.

Kynurenine diminishes the ischemia-induced histological and electrophysiological deficits in the rat hippocampus.

The neuroprotective effect of L-kynurenine sulfate (KYN), a precursor of kynurenic acid (KYNA, a selective N-methyl-D-aspartate receptor antagonist), was studied. KYN (300 mg/kg i.p.

Evans Blue fluorescence permits the rapid visualization of non-intact cells in the perilesional rim of cold-injured rat brain.

A focal cold lesion-induced injury, i.e., a model of focal vasogenic brain edema, enhances the permeability of the blood-brain barrier and cell membrane in the perilesional rim.

Spatiotemporal changes of the herpes simplex virus entry receptor nectin-1 in murine brain during postnatal development.

Herpes simplex virus (HSV) is known to replicate within the limbic system and to alter behavior in both humans and experimental animals. However, the reason why the virus selectively damages this anatomical, developmental, and functional neural unit remains a mystery. Nor is it known why herpes simplex encephalitis fails to respect these neuroanatomical boundaries in newborns.

Effects of dehydroepiandrosterone sulfate on the evoked cortical activity of controls and of brain-injured rats.

1. Dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are sex hormone precursors which exert marked neurotrophic and/or neuroprotective activity in the central nervous system (CNS). 2.

Endomorphin-2, an endogenous tetrapeptide, protects against Abeta1-42 in vitro and in vivo.

The underlying cause of Alzheimer's disease (AD) is thought to be the beta-amyloid aggregates formed mainly by Abeta1-42 peptide. Protective pentapeptides [e.g.

Hippocampal (CA1) activities in Wistar rats from different vendors. Fundamental differences in acute ischemia.

Two-vessel occlusion, a frequently used model of global cerebral ischemia in rats, results in a dysfunction predominantly within the CA1 field of the hippocampus; it induces many processes with different time-scales. However, the great divergence in the results of the studies reported in the literature suggests valuable differences in response to hypoperfusion-induced ischemia among the laboratory rats used in these studies. In the present work, the acute effects of two-carotid occlusion-induced global ischemia (2VO) on the CA3 stimulation-evoked population spike activity in the CA1 region of Wistar rats from different suppliers (Charles-River and Harlan) were compared.

Dehydroepiandrosterone sulfate is neuroprotective when administered either before or after injury in a focal cortical cold lesion model.

Dehydroepiandrosterone and its sulfate (DHEAS) are sex hormone precursors that exert marked neurotrophic and/or neuroprotective activity in the central nervous system. The present study evaluated the effects of DHEAS and 17beta-estradiol (E2) in a focal cortical cold lesion model, in which DHEAS (50 mg/kg, sc) and E2 (35 mg/kg, sc) were administered either as pretreatment (two subsequent injections 1 d and 1 h before lesion induction) or posttreatment (immediately after lesion induction). The focal cortical cold lesion was induced in the primary motor cortex by means of a cooled copper cylinder placed directly onto the cortical surface.

Use of a recombinant pseudorabies virus to analyze motor cortical reorganization after unilateral facial denervation.

A unilateral facial nerve injury (n7x) was found to influence the transcallosal spread of the attenuated strain of pseudorabies virus (PRV Bartha) from the affected (left) primary motor cortex (MI) to the contralateral MI of rats. We used Ba-DupLac, a recombinant PRV strain, for the tracing experiments since this virus was demonstrated to exhibit much more restricted transportation kinetics than that of PRV Bartha, and is therefore more suitable for studies of neuronal plasticity. Ba-Duplac injection primarily infected several neurons around the penetration channel, but hardly any transcallosally infected neurons were observed in the contraleral MI.

Facial nerve injury induces facilitation of responses in both trigeminal and facial nuclei of rat.

A study was made of the effects of facial nerve transection on trigeminal stimulation- evoked field potentials in the principal trigeminal (Pr5) and facial nuclei (7) in rats. Although the transected branch of the facial nerve contains pure motoric efferents, it resulted in enhanced responses in both Pr5 and 7. These electrophysiological results suggest a functional circuitry involving the whiskers, trigeminal nerve, Pr5 and 7 and the facial nerve as efferent.