Ischemia-induced cell depolarization: does the hyperpolarization-activated cation channel HCN2 affect the outcome after stroke in mice?

Background: Brain ischemia is known to include neuronal cell death and persisting neurological deficits. A lack of oxygen and glucose are considered to be key mediators of ischemic neurodegeneration while the exact mechanisms are yet unclear. In former studies the expression of two different two-pore domain potassium (K2P) channels (TASK1, TREK1) were shown to ameliorate neuronal damage due to cerebral ischemia.

Evans syndrome associated with sterile inflammation of the central nervous system: a case report.

Introduction: Evans syndrome is a rare hematological disease commonly defined as Coombs-positive hemolytic anemia and immune thrombocytopenia. Pathophysiology of this disease involves decreased cluster of differentiation (CD)4+ T-helper cell counts, increased CD8+ T-suppressor cell counts, a decreased CD4/CD8 ratio, and reduced serum immunoglobulin G, M and A levels - indicating a complex immune dysregulation. Association with other autoimmune diseases has been described although involvement of the central nervous system has not been reported so far.

Long-term effects of dalfampridine in patients with multiple sclerosis.

Background/objective: Dalfampridine is the extended-release formulation of 4-aminopyridine and is approved for the symptomatic treatment of impaired mobility in patients with multiple sclerosis. Our aim was to examine the short- and long-term effects of treatment with dalfampridine on motoric and cognitive assessment parameters of multiple sclerosis (MS) patients over 9-12 months.

Methods: Fifty-two patients with MS with an EDSS between 4.

CD4+NKG2D+ T cells exhibit enhanced migratory and encephalitogenic properties in neuroinflammation.

Migration of encephalitogenic CD4(+) T lymphocytes across the blood-brain barrier is an essential step in the pathogenesis of multiple sclerosis (MS). We here demonstrate that expression of the co-stimulatory receptor NKG2D defines a subpopulation of CD4(+) T cells with elevated levels of markers for migration, activation, and cytolytic capacity especially when derived from MS patients. Furthermore, CD4(+)NKG2D(+) cells produce high levels of proinflammatory IFN-γ and IL-17 upon stimulation.

A splice variant of the two-pore domain potassium channel TREK-1 with only one pore domain reduces the surface expression of full-length TREK-1 channels.

We have identified a novel splice variant of the human and rat two-pore domain potassium (K2P) channel TREK-1. The splice variant TREK-1e results from skipping of exon 5, which causes a frame shift in exon 6. The frame shift produces a novel C-terminal amino acid sequence and a premature termination of translation, which leads to a loss of transmembrane domains M3 and M4 and of the second pore domain.

Excitotoxic neuronal cell death during an oligodendrocyte-directed CD8+ T cell attack in the CNS gray matter.

Background: Neural-antigen reactive cytotoxic CD8+ T cells contribute to neuronal dysfunction and degeneration in a variety of inflammatory CNS disorders. Facing excess numbers of target cells, CNS-invading CD8+ T cells cause neuronal cell death either via confined release of cytotoxic effector molecules towards neurons, or via spillover of cytotoxic effector molecules from 'leaky' immunological synapses and non-confined release by CD8+ T cells themselves during serial and simultaneous killing of oligodendrocytes or astrocytes.

Methods: Wild-type and T cell receptor transgenic CD8+ T cells were stimulated in vitro, their activation status was assessed by flow cytometry, and supernatant glutamate levels were determined using an enzymatic assay.

Targeting ion channels for the treatment of autoimmune neuroinflammation.

Pharmacological targeting of ion channels has long been recognized as an attractive strategy for the treatment of various diseases. Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system with a prominent neurodegenerative component. A multitude of different cell types are involved in the complex pathophysiology of this disorder, including cells of the immune system (e.

Protein kinase Cβ as a therapeutic target stabilizing blood-brain barrier disruption in experimental autoimmune encephalomyelitis.

Disruption of the blood-brain barrier (BBB) is a hallmark of acute inflammatory lesions in multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis. This disruption may precede and facilitate the infiltration of encephalitogenic T cells. The signaling events that lead to this BBB disruption are incompletely understood but appear to involve dysregulation of tight-junction proteins such as claudins.

Endothelial TWIK-related potassium channel-1 (TREK1) regulates immune-cell trafficking into the CNS.

The blood-brain barrier (BBB) is an integral part of the neurovascular unit (NVU). The NVU is comprised of endothelial cells that are interconnected by tight junctions resting on a parenchymal basement membrane ensheathed by pericytes, smooth muscle cells and a layer of astrocyte end feet. Circulating blood cells, such as leukocytes, complete the NVU.

4-Aminopyridine ameliorates mobility but not disease course in an animal model of multiple sclerosis.

Neuropathological changes following demyelination in multiple sclerosis (MS) lead to a reorganization of axolemmal channels that causes conduction changes including conduction failure. Pharmacological modulation of voltage-sensitive potassium channels (K(V)) has been found to improve conduction in experimentally induced demyelination and produces symptomatic improvement in MS patients. Here we used an animal model of autoimmune inflammatory neurodegeneration, namely experimental autoimmune encephalomyelitis (EAE), to test the influence of the K(V)-inhibitor 4-aminopyridine (4-AP) on various disease and immune parameters as well as mobility in MOG₃₅₋₅₅ immunized C57Bl/6 mice.

Bound states in sharply bent waveguides: analytical and experimental approach.

Quantum wires and electromagnetic waveguides possess common features since their physics is described by the same wave equation. We exploit this analogy to investigate experimentally with microwave waveguides and theoretically with the help of an effective potential approach the occurrence of bound states in sharply bent quantum wires. In particular, we compute the bound states, study the features of the transition from a bound to an unbound state caused by the variation of the bending angle, and determine the critical bending angles at which such a transition takes place.

Induction of death of leukemia cells by TW-74, a novel derivative of chloro-naphthoquinone.

We have previously shown that a 2-chloro-1,4-naphthoquinone derivative (TW-92) induces cell death in leukemia cells. TW-92 exhibited relatively high selectivity towards primary Acute Myeloid Leukemia (AML) cells, as compared to normal mononuclear cells. In view of the selectivity of this family of naphthoquinones, novel chloroaminophenylnaphthoquinone isomers with different methyl substitutions on the phenyl ring were synthesized, and their effect on leukemia cells was tested.

Regulatory T cells are strong promoters of acute ischemic stroke in mice by inducing dysfunction of the cerebral microvasculature.

We have recently identified T cells as important mediators of ischemic brain damage, but the contribution of the different T-cell subsets is unclear. Forkhead box P3 (FoxP3)-positive regulatory T cells (Tregs) are generally regarded as prototypic anti-inflammatory cells that maintain immune tolerance and counteract tissue damage in a variety of immune-mediated disorders. In the present study, we examined the role of Tregs after experimental brain ischemia/reperfusion injury.

Identification of two-pore domain potassium channels as potent modulators of osmotic volume regulation in human T lymphocytes.

Many functions of T lymphocytes are closely related to cell volume homeostasis and regulation, which utilize a complex network of membrane channels for anions and cations. Among the various potassium channels, the voltage-gated K(V)1.3 is well known to contribute greatly to the osmoregulation and particularly to the potassium release during the regulatory volume decrease (RVD) of T cells faced with hypotonic environment.

Trace formula for chaotic dielectric resonators tested with microwave experiments.

We measured the resonance spectra of two stadium-shaped dielectric microwave resonators and tested a semiclassical trace formula for chaotic dielectric resonators proposed by Bogomolny et al. [Phys. Rev.

The TASK1 channel inhibitor A293 shows efficacy in a mouse model of multiple sclerosis.

The two-pore domain potassium channel TASK1 (KCNK3) has recently emerged as an important modulator in autoimmune CNS inflammation. Previously, it was shown that T lymphocytes obtained from TASK1(-/-) mice display impaired T cell effector functions and that TASK1(-/-) mice show a significantly reduced disease severity in myelin oligodendrocyte glycoprotein (MOG(35-55)) peptide induced experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. We here evaluate a potent and specific TASK1 channel inhibitor, A293, which caused a dose-dependent reduction of T cell effector functions (cytokine production and proliferation).

Application of a trace formula to the spectra of flat three-dimensional dielectric resonators.

The length spectra of flat three-dimensional dielectric resonators of circular shape were determined from a microwave experiment. They were compared to a semiclassical trace formula obtained within a two-dimensional model based on the effective index of refraction approximation and a good agreement was found. It was necessary to take into account the dispersion of the effective index of refraction for the two-dimensional approximation.

CD4(+) CD25(+) FoxP3(+) regulatory T cells suppress cytotoxicity of CD8(+) effector T cells: implications for their capacity to limit inflammatory central nervous system damage at the parenchymal level.

Background: CD4(+) CD25(+) forkhead box P3 (FoxP3)(+) regulatory T cells (T reg cells) are known to suppress adaptive immune responses, key control tolerance and autoimmunity.

Methods: We challenged the role of CD4(+) T reg cells in suppressing established CD8(+) T effector cell responses by using the OT-I/II system in vitro and an OT-I-mediated, oligodendrocyte directed ex vivo model (ODC-OVA model).

Results: CD4(+) T reg cells dampened cytotoxicity of an ongoing CD8(+) T effector cell attack in vitro and within intact central nervous system tissue ex vivo.

PT symmetry and spontaneous symmetry breaking in a microwave billiard.

We demonstrate the presence of parity-time (PT) symmetry for the non-Hermitian two-state Hamiltonian of a dissipative microwave billiard in the vicinity of an exceptional point (EP). The shape of the billiard depends on two parameters. The Hamiltonian is determined from the measured resonance spectrum on a fine grid in the parameter plane.

IL-17 silencing does not protect nonobese diabetic mice from autoimmune diabetes.

The long-held view that many autoimmune disorders are primarily driven by a Th1 response has been challenged by the discovery of Th17 cells. Since the identification of this distinct T cell subset, Th17 cells have been implicated in the pathogenesis of several autoimmune diseases, including multiple sclerosis and rheumatoid arthritis. Type 1 diabetes has also long been considered a Th1-dependent disease.

Double-slit experiments with microwave billiards.

Single and double-slit experiments are performed with two microwave billiards with the shapes of a rectangle and a quarter stadium, respectively. The classical dynamics of the former is regular, whereas that of the latter is chaotic. Microwaves can leave the billiards via slits in the boundary, forming interference patterns on a screen.

[Pregabalin and gabapentin in multiple sclerosis: clinical experiences and therapeutic implications].

Background: Due to a plethora of additional symptoms patients with multiple sclerosis (MS) receive symptomatic treatment besides disease-modifying therapies. Among the substances which are commonly used are ion channel modulators (e. g.

Volume regulation of murine T lymphocytes relies on voltage-dependent and two-pore domain potassium channels.

A variety of ion channels are supposed to orchestrate the homoeostatic volume regulation in T lymphocytes. However, the relative contribution of different potassium channels to the osmotic volume regulation and in particular to the regulatory volume decrease (RVD) in T cells is far from clear. This study explores a putative role of the newly identified K(2P) channels (TASK1, TASK2, TASK3 and TRESK) along with the voltage-gated potassium channel K(V)1.