A Monoclonal Anti-HMGB1 Antibody Attenuates Neurodegeneration in an Experimental Animal Model of Glaucoma.

Neuroinflammation is a crucial process for the loss of retinal ganglion cells (RGC), a major characteristic of glaucoma. High expression of high-mobility group box protein 1 (HMGB1) plays a detrimental role in inflammatory processes and is elevated in the retinas of glaucoma patients. Therefore, this study aimed to investigate the effects of the intravitreal injection of an anti-HMGB1 monoclonal antibody (anti-HMGB1 Ab) in an experimental animal model of glaucoma.

Chronic social defeat stress causes retinal vascular dysfunction.

Purpose: The roles of vascular dysfunction and chronic stress have been extensively discussed in the pathophysiology of glaucoma. Our aim was to test whether chronic stress causes retinal vascular dysfunction and therewith induces retinal ganglion cells (RGCs) loss.

Methods: Twelve mice underwent chronic social defeat (CSD) stress, while 12 mice received control treatment only.

Does granulocyte-colony stimulating factor stimulate peripheral nerve regeneration? An experimental study on traumatic lesion of the sciatic nerve in rats.

Aim Of The Study: To analyse the therapeutic potential of granulocyte-colony stimulating factor (G-CSF) treatment using a rat model of traumatic sciatic nerve lesion.

Clinical Rationale For The Study: G-CSF has proven strong neurotrophic properties in various models of ischaemic and traumatic brain injury. Fewer studies exist regarding the influence of G-CSF on posttraumatic peripheral nerve regeneration.

Correction: The genomic and clinical landscape of fetal akinesia.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Intracranial multiple myeloma may imitate subdural hemorrhage: How to overcome diagnostic limitations and avoid errors in treatment.

Background: Although the diagnosis of subdural hematoma is usually straightforward, occasionally it may be erroneous, leading to mistakes in the treatment. For example, leptomeningeal malignancies, even in the absence of bleeding, may clinically and radiologically mimic subdural hemorrhage.

Objective: To stress the importance of not only intuitive thinking but also in analytic thinking in appropriate and accurate treatment strategies.

Intravitreal injection of β-crystallin B2 improves retinal ganglion cell survival in an experimental animal model of glaucoma.

Purpose of this study was to investigate firstly specific proteomic changes within the retina in the course of an animal glaucoma model and to identify secondly new approaches for neuroprotective, therapeutic options in glaucoma by addressing those specific changes. Intraocular pressure was elevated through cauterization of episcleral veins in adult Sprague Dawley rats. Molecular and morphological changes were surveyed using mass spectrometry, optical coherence tomography as well as immunohistochemical cross section- and flat mount stainings.

Quantification of muscle pathology in infantile Pompe disease.

The effects of enzyme replacement therapy (ERT) in infantile Pompe disease are variable, necessitating the identification of biomarkers to assess the severity of disease and response to ERT. The aims of this study were to investigate whether quantification of muscle pathology in infantile Pompe disease prior to and during ERT is feasible at the light microscope, and to develop a score that summarizes the degree of muscle pathology in a comprehensive manner from PAS-stained resin sections alone. We, therefore, determined glycogen load, extent of muscle fibre disruption, and amount of autophagic vacuoles in resin-embedded muscle biopsy specimens from 11 infantile Pompe patients and 2 with early childhood phenotype by quantitative methods, correlated the findings with ultrastructural analyses, compared PAS-stained resin sections with conventional PAS-stained cryosections, and related the quantified degree of muscle damage from infantile patients to the effects of ERT.

Immune response after intermittent minimally invasive intraocular pressure elevations in an experimental animal model of glaucoma.

Background: Elevated intraocular pressure (IOP), as well as fluctuations in IOP, is a main risk factor for glaucoma, but its pathogenic effect has not yet been clarified. Beyond the multifactorial pathology of the disease, autoimmune mechanisms seem to be linked to retinal ganglion cell (RGC) death. This study aimed to identify if intermittent IOP elevations in vivo (i) elicit neurodegeneration, (ii) provokes an immune response and (iii) whether progression of RGC loss can be attenuated by the B lymphocyte inhibitor Belimumab.

Murine genetic deficiency of neuronal nitric oxide synthase (nNOS(-/-) ) and interstitial cells of Cajal (W/W(v) ): Implications for achalasia?

Background And Aim: Nitric oxide (NO) is an important inhibitory mediator of esophageal function, and its lack leads to typical features of achalasia. In contrast, the role of intramuscular interstitial cells of Cajal (ICC-IM) and vasoactive intestinal peptide (VIP) in lower esophageal sphincter (LES) function is still controversial. Therefore, we examined the function and morphology of the LES in vivo in NO-deficient (nNOS(-/-) ), ICC-IM-deficient (W/W(v) )-, and wild-type (WT) mice.

Dynamics, alterations, and consequences of minimally invasive intraocular pressure elevation in rats.

Purpose: An important, yet not exclusive, aspect of primary open angle glaucoma is elevated intraocular pressure (IOP) profiles within fluctuations and pressure peaks. The study aimed at establishing minimally invasive methods for recurrent IOP elevation in rats to investigate the impact of IOP dynamics and pathomorphologic retinal alterations during and after IOP elevation.

Methods: Intraocular pressure was elevated unilaterally in Long Evans rats to a level of ≈35 mm Hg for 1 hour in a total of 30 manipulations within 6 weeks, by using two methods: (1) suction-cup oculopression and (2) loop-adjusted oculopression.

Distribution of the hematopoietic growth factor G-CSF and its receptor in the adult human brain with specific reference to Alzheimer's disease.

The granulocyte colony-stimulating factor (G-CSF), being a member of the hematopoietic growth factor family, is also critically involved in controlling proliferation and differentiation of neural stem cells. Treatment with G-CSF has been shown to result in substantial neuroprotective and neuroregenerative effects in various experimental models of acute and chronic diseases of the central nervous system. Although G-CSF has been tested in a clinical study for treatment of acute ischemic stroke, there is only fragmentary data on the distribution of this cytokine and its receptor in the human brain.

How to treat tumefactive demyelinating disease?

Glioma-like inflammatory demyelinating lesions can be found in patients with pre-diagnosed multiple sclerosis, but they have also been described as an isolated disease entity. The initial diagnostic work-up usually includes a biopsy for histopathological analysis. However, even after unambiguous histopathologic classification, tumefactive lesions pose a therapeutic challenge.

Immune response against ocular tissues after immunization with optic nerve antigens in a model of autoimmune glaucoma.

Purpose: In recent years, numerous studies have investigated the involvement of immunological mechanisms in glaucoma. Until now, it has not been determined whether the altered antibody pattern detected in patients is harmful to retinal ganglion cells (RGCs) or triggers disease formation in any way. In a model of experimental autoimmune glaucoma, RGC loss can be induced through immunization with certain ocular antigens.

Retinal ganglion cell loss is accompanied by antibody depositions and increased levels of microglia after immunization with retinal antigens.

Background: Antibodies against retinal and optic nerve antigens are detectable in glaucoma patients. Recent studies using a model of experimental autoimmune glaucoma demonstrated that immunization with certain ocular antigens causes an immun-mediated retinal ganglion cell loss in rats.

Methodology/principal Findings: Rats immunized with a retinal ganglion cell layer homogenate (RGA) had a reduced retinal ganglion cell density on retinal flatmounts (p = 0.

Distribution of granulocyte-monocyte colony-stimulating factor and its receptor α-subunit in the adult human brain with specific reference to Alzheimer's disease.

Granulocyte-monocyte colony-stimulating factor (GM-CSF) is a member of the hematopoietic growth factor family, promoting proliferation and differentiation of hematopoietic progenitor cells of the myeloid lineage. In recent years, GM-CSF has also proved to be an important neurotrophic factor in the central nervous system (CNS) via binding to the GM-CSF receptor (GM-CSF R). Furthermore, studies on rodent CNS revealed a wide distribution of both the major binding α-subunit of the GM-CSF R (GM-CSF Rα) and its ligand.

A new mitochondrial point mutation in the transfer RNA(Lys) gene associated with progressive external ophthalmoplegia with impaired respiratory regulation.

We report a novel heteroplasmic point mutation G8299A in the gene for mitochondrial tRNA(Lys) in a patient with progressive external ophthalmoplegia complicated by recurrent respiratory insufficiency. Biochemical analysis of respiratory chain complexes in muscle homogenate showed a combined complex I and IV deficiency. The transition does not represent a known neutral polymorphism and affects a position in the tRNA acceptor stem which is conserved in primates, leading to a destabilization of this functionally important domain.