Heterozygous Pyrin (MEFV) E148Q allele carriers indicate a reduced glaucoma risk for Turkish population: a prospective clinical analysis.

Purpose: The MEFV gene encodes pyrin, a protein linked to increased severity of symptoms in Familial Mediterranean Fever (FMF). We consider that inflammation due to MEFV variants would increase eye inflammation and damage aqueous humor regulation. The present study is the first analysis investigating a MEFV (E148Q) variant as a marker protecting from glaucoma.

Ocular Effects of Sildenafil in Naïve Mice and a Mouse Model of Optic Nerve Crush.

Purpose: To investigate the potential neuroprotective effect of sildenafil on the ocular circulation in mice with/without optic nerve crush (ONC).

Methods: Male adult mice (n = 63) were treated with intravitreal (IVT) sildenafil 24 μg/3 μL, intraperitoneal (IP) sildenafil 24 μg/300 μL, or IP saline immediately before right ONC induction (ONC group). A second group (n = 123) received the same treatments without ONC induction (naïve group).

Protective Effect of TLR4 Ablation against Corneal Neovascularization following Chemical Burn in a Mouse Model.

Purpose: To determine whether Toll-like receptor 4 knockout protects mice from corneal neovascularization following chemical injury compared to wild-type (WT) mice.

Methods: A chemical burn (75% silver nitrate, 25% potassium nitrate) was created under anesthesia in the central right cornea of 32 WT and 31 Toll-like receptor 4 knockout mice. Corneal neovascularization was evaluated at 3, 4, 6, 8, 10, and 35 days after injury using digital photography, fluorescein angiography, gelatin perfusion with fluorescence vascular imaging, immunofluorescence staining, and molecular analysis.

Quantitative Analysis of Kynurenine Aminotransferase II in the Adult Rat Brain Reveals High Expression in Proliferative Zones and Corpus Callosum.

Kynurenic acid, a metabolite of the kynurenine pathway of tryptophan degradation, acts as an endogenous antagonist of alpha7 nicotinic and NMDA receptors and is implicated in a number of neurophysiological and neuropathological processes including cognition and neurodegenerative events. Therefore, kynurenine aminotransferase II (KAT II/AADAT), the enzyme responsible for the formation of the majority of neuroactive kynurenic acid in the brain, has prompted significant interest. Using immunohistochemistry, this enzyme was localized primarily in astrocytes throughout the adult rat brain, but detailed neuroanatomical studies are lacking.

Reduced kynurenine pathway metabolism and cytokine expression in the prefrontal cortex of depressed individuals.

Background: Neuroinflammatory processes are increasingly believed to participate in the pathophysiology of a number of major psychiatric diseases, including depression. Immune activation stimulates the conversion of the amino acid tryptophan to kynurenine, leading to the formation of neuroactive metabolites, such as quinolinic acid and kynurenic acid. These compounds affect glutamatergic neurotransmission, which plays a prominent role in depressive pathology.

SUR1-Associated Mechanisms Are Not Involved in Ischemic Optic Neuropathy 1 Day Post-Injury.

Ischemia-reperfusion injury after central nervous system (CNS) injury presents a major health care challenge with few promising treatments. Recently, it has become possible to reduce edema after CNS injury by antagonizing a sulfonylurea receptor 1 (SUR1) regulated ion channel expressed after injury. SUR1 upregulation after injury is a necessary precondition for the formation of this channel, and has been implicated in white matter injury after clinical spinal cord trauma.

Expansion of brain T cells in homeostatic conditions in lymphopenic Rag2(-/-) mice.

The concept of the brain as an immune privileged organ is rapidly evolving in light of new findings outlining the sophisticated relationship between the central nervous and the immune systems. The role of T cells in brain development and function, as well as modulation of behavior has been demonstrated by an increasing number of studies. Moreover, recent studies have redefined the existence of a brain lymphatic system and the presence of T cells in specific brain structures, such as the meninges and choroid plexus.

TLR4 Expression Is Associated with Left Ventricular Dysfunction in Patients Undergoing Coronary Artery Bypass Surgery.

Introduction: Toll-like receptor 4 (TLR4) is an innate immune receptor expressed in immune cells and the heart. Activation of the immune system following myocardial ischemia causes the release of proinflammatory mediators that may negatively influence heart function.

Aim: The aim of this study is to determine whether TLR4 is activated in peripheral monocytes and heart tissue taken from patients with varying degrees of myocardial dysfunction caused by coronary artery diseases and scheduled for coronary artery bypass graft (CABG) surgery before 12 months following operation.

Toll-like receptor-4 knockout mice are more resistant to optic nerve crush damage than wild-type mice.

Background: This study aims to investigate the role of the inflammatory response following optic nerve crush (ONC) in knockout mice for the toll-like receptor-4 gene (TLR4-/-) compared to wild-type (WT) mice.

Methods: ONC was induced in TLR4-/- and C57BL6 WT mice. Histological sections of the retina and optic nerve were analysed on days 1, 3 or 21 after injury.

Relative neuroprotective effects hyperbaric oxygen treatment and TLR4 knockout in a mouse model of temporary middle cerebral artery occlusion.

Purpose: To examine the effects of hyperbaric oxygen (HBO) therapy and knockout of toll-like receptor 4 (TLR4) on the outcome of temporary middle cerebral artery occlusion (MCAO) in a mouse model.

Materials And Methods: MCAO was induced in anesthetized male C57Bl/6 mice (WT) and TLR4 knockout mice (TLR4(-/-)) using an intra-arterial filament method. After 30 or 90 min, the filament was removed, and the mice were given either no treatment (WT and TLR4(-/-) groups) or HBO (WT only).

Effect of intravitreal injection of bevacizumab on optic nerve head leakage and retinal ganglion cell survival in a mouse model of optic nerve crush.

Purpose: To evaluate the effect of bevacizumab, a VEGF inhibitor, on optic nerve edema and retinal ganglion cell (RGC) loss in a mouse model of optic nerve crush (ONC).

Methods: Two hundred C57BL/6 wild-type mice were anesthetized. Right ONC was induced in 150 mice, of which half (n = 75) received an intravitreal injection of bevacizumab immediately thereafter and half (n = 75) did not.

PGJ(2) provides prolonged CNS stroke protection by reducing white matter edema.

Few clinically effective approaches reduce CNS-white matter injury. After early in-vivo white matter infarct, NFκB-driven pro-inflammatory signals can amplify a relatively small amount of vascular damage, resulting in progressive endothelial dysfunction to create a severe ischemic lesion. This process can be minimized by 15-deoxy-Δ(12,14)-prostaglandin J2 (PGJ(2)), an analog of the metabolically active PGD(2) metabolite.

Expression and regulation in the brain of the chemokine CCL27 gene locus.

The chemokine CCL27 has chemoattractant properties for memory T cells and has been implicated in skin allergic reactions. The present study reports the expression in the brain of two CCL27 splice variants localized in the cerebral cortex and limbic regions. CCL27-like immunoreactivity was identified mainly in neurons.

Mapping the binding site on small ankyrin 1 for obscurin.

Small ankyrin 1 (sAnk1), an integral protein of the sarcoplasmic reticulum encoded by the ANK1 gene, binds with nanomolar affinity to the C terminus of obscurin, a giant protein surrounding the contractile apparatus in striated muscle. We used site-directed mutagenesis to characterize the binding site on sAnk1, specifically addressing the role of two putative amphipathic, positively charged helices. We measured binding qualitatively by blot overlay assays and quantitatively by surface plasmon resonance and showed that both positively charged sequences are required for activity.

Structure/function analyses of human serum paraoxonase (HuPON1) mutants designed from a DFPase-like homology model.

Human serum paraoxonase (HuPON1) is a calcium-dependent enzyme that hydrolyzes esters, including organophosphates and lactones, and exhibits anti-atherogenic properties. A few amino acids have been shown to be essential for the enzyme's arylesterase and organophosphatase activities. Until very recently, a three-dimensional model was not available for HuPON1, so functional roles have not been assigned to those residues.

A capillary electrophoresis technique for evaluating botulinum neurotoxin B light chain activity.

Botulinum neurotoxin B (BoNT/B) produces muscle paralysis by cleaving synaptobrevin/vesicle-associated membrane protein (VAMP), an 18-kDa membrane-associated protein located on the surface of small synaptic vesicles. A capillary electrophoresis (CE) assay was developed to evaluate inhibitors of the proteolytic activity of BoNT/B with the objective of identifying suitable candidates for treatment of botulism. The assay was based on monitoring the cleavage of a peptide that corresponds to residues 44-94 of human VAMP-2 (V51) following reaction with the catalytic light chain (LC) of BoNT/B.