Influenza virus infection is a rare cause of neurological complications, with acute necrotizing encephalopathy (ANE) being among the deadliest. Due to the low incidence of ANE, literature about its association with influenza B infection is limited. We present the case of a 29-year-old previously healthy man with an imaging and clinical diagnosis of influenza B virus infection and sudden decline in mental status.
View Article and Find Full Text PDFImpulse control disorder (ICD) has been linked to dopamine agonist use in patients with Parkinson's disease. Increased creativity is another cognitive side effect of dopaminergic therapy. While ICD is well recognized in the literature, enhanced creativity as a positive phenomenon is underreported because it does not negatively affect the patients' quality of life.
View Article and Find Full Text PDFThe programmed cell death ligand-1 antibody, atezolizumab, is an immune checkpoint inhibitor approved for the treatment of various cancers. Herein, we describe a case of an 87-year-old man with advanced urothelial carcinoma. After surgery, atezolizumab was given.
View Article and Find Full Text PDFOver the last years, studies on microglia cell function in chronic neuro-inflammation and neuronal necrosis pointed towards an eminent role of these cells in Multiple Sclerosis, Parkinson's and Alzheimer's Disease. It was found, that microglia cell activity can be stimulated towards a pro- or an anti-inflammatory profile, depending on the stimulating signals. Therefore, investigation of receptors expressed by microglia cells and ligands influencing their activation state is of eminent interest.
View Article and Find Full Text PDFHonokiol has been used in traditional medicine for the treatment of inflammatory diseases. Activation of glial cells plays an essential role in neurodegenerative disorders. In this study, we show that Honokiol reduces the inflammatory response to LPS of primary cultures of microglia and astrocytes through the inhibition of pro-inflammatory mediators (iNOS, IL-6, IL-1β and TNF-α) and the simultaneous stimulation of anti-inflammatory cytokines (IL-10).
View Article and Find Full Text PDFThe FDA-approved antidepressant and smoking cessation drug bupropion is known to inhibit dopamine and norepinephrine reuptake transporters, as well as nicotinic acetylcholine receptors (nAChRs) which are cation-conducting members of the Cys-loop superfamily of ion channels, and more broadly pentameric ligand-gated ion channels (pLGICs). In the present study, we examined the ability of bupropion and its primary metabolite hydroxybupropion to block the function of cation-selective serotonin type 3A receptors (5-HTRs), and further characterized bupropion's pharmacological effects at these receptors. Mouse 5-HTRs were heterologously expressed in HEK-293 cells or Xenopus laevis oocytes for equilibrium binding studies.
View Article and Find Full Text PDFIntroduction: Measurement of static pupillary size in the ICU is of importance in cases of acutely expanding intracranial mass lesions. The inaccuracies with subjective assessment of pupillary size by medical personnel preclude its use in emergent neurological situations.
Objective: To determine if the ratio of pupil to limbus diameter (PLD ratio) measured by a two-box method is a reliable measure of pupil size for detecting early anisocoria and measuring pupillary changes.
Typical West Nile virus paralysis is characterized by muscle weakness, decreased tone, and loss of deep tendon reflexes attributed to destruction of anterior horn cells. Two cases in which deep tendon reflexes were initially preserved in the presence of profound and persistent muscle weakness are presented here. In both cases, deep tendon reflexes were later severely attenuated or lost, while weakness of the involved muscles remained profound and unchanged.
View Article and Find Full Text PDFMultiple sclerosis (MS) is a disease of the central nervous system that is characterized by the demyelination of neuronal axons. Four different patterns of demyelination have been described, showing the heterogeneity in the immunopathologic processes involved in the demyelination. This review will focus on reactive oxygen species (ROS)-related inflammation in MS.
View Article and Find Full Text PDFPrevious studies have shown that glial cell line-derived neurotrophic factor (GDNF) family ligands (GFL) are potent survival factors for dopaminergic neurons and motoneurons with therapeutic potential for Parkinson's disease. However, little is known about direct influences of the GFL on microglia function, which are known to express part of the GDNF receptor system. Using RT-PCR and immunohistochemistrym we investigated the expression of the GDNF family receptor alpha 1 (GFR alpha) and the coreceptor transmembrane receptor tyrosine kinase (RET) in rat microglia in vitro as well as the effect of GFL on the expression of proinflammatory molecules in LPS activated microglia.
View Article and Find Full Text PDFBackground: Brain inflammation plays a central role in multiple sclerosis (MS). Dimethylfumarate (DMF), the main ingredient of an oral formulation of fumaric acid esters with proven therapeutic efficacy in psoriasis, has recently been found to ameliorate the course of relapsing-remitting MS. Glial cells are the effector cells of neuroinflammation; however, little is known of the effect of DMF on microglia and astrocytes.
View Article and Find Full Text PDFBacterial meningitis is characterized by an inflammation of the meninges and continues to be an important cause of mortality and morbidity. Meningeal cells cover the cerebral surface and are involved in the first interaction between pathogens and the brain. Little is known about the role of meningeal cells and the expression of antimicrobial peptides in the innate immune system.
View Article and Find Full Text PDFPrevious studies have shown that activin A, a neuroprotective cytokine and dimeric polypeptide composed of two betaA subunits, is elevated in the cerebrospinal fluid of patients suffering from bacterial meningitis. In this study, to elucidate further the functional significance and pathophysiological implications of these findings, we demonstrated that microglial cells are not only the source but also the target cells of activin A in the central nervous system: immunohistochemistry and RT-PCR revealed expression of activin subunit betaA mRNA as well as activin receptor type I and type II mRNA in rat microglia in vitro. Further studies showed that activin enhances microglial proliferation and decreases the gamma-interferon-induced synthesis of nitric oxide, one of several microglial mediators involved in the inflammatory response in microglia activation.
View Article and Find Full Text PDFErythropoietin is a hematopoietic cytokine which is also produced in the brain under hypoxia. Since this pathology is associated with glial cell activation and release of cytotoxic molecules, we investigated the expression of EPO receptors (EPO-R) and effects of erythropoietin on microglial cell functions in vitro using RT-PCR, Western immunoblotting, nitric oxide measurement, tumor necrosis factor-alpha-(TNF-alpha)-ELISA and gel shift assay analyses. Furthermore, we examined if erythropoietin could modulate proliferation of microglia.
View Article and Find Full Text PDFAntimicrobial peptides are intrinsic to the innate immune system in many organ systems, but little is known about their expression in the central nervous system. We examined cerebrospinal fluid (CSF) and serum from patients with active bacterial meningitis to assess antimicrobial peptides and possible bactericidal properties of the CSF. We found antimicrobial peptides (human cathelicidin LL-37) in the CSF of patients with bacterial meningitis but not in control CSF.
View Article and Find Full Text PDFParkinson's disease (PD) is a common neurodegenerative disorder characterized by a selective loss of dopaminergic neurons in the substantia nigra (SN). It has been suggested that microglial inflammation augments the progression of PD. Neuromelanin (NM), a complex polymer pigment found in catecholaminergic neurons, has sparked interest because of the suggestion that NM is involved in cell death in Parkinson's disease, possibly via microglia activation.
View Article and Find Full Text PDFThe peptide hormone angiotensin (A)-II, the major effector peptide of the renin-angiotensin system (RAS), is well established to play a pivotal role in the systemic regulation of blood pressure, fluid, and electrolyte homeostasis. Recent biochemical and neurophysiologic studies have documented local intrinsic angiotensin-generating systems in organs and tissues such as the brain, retina, bone marrow, liver, and pancreas. The locally generated angiotensin peptides have multiple and novel actions including stimulating cell growth and anti-proliferative and/or antiapoptotic actions.
View Article and Find Full Text PDFNeuromelanin (NM) accumulates as a function of age in normal human substantia nigra (SN) but is relatively depleted in the SN of patients with Parkinson disease (PD). Several studies have been performed to further our understanding of the role of NM in neuronal aging and neurodegenerative mechanisms of PD. To this purpose, NM from human SN was isolated and its structure and molecular interactions were investigated.
View Article and Find Full Text PDFNeuromelanin accumulates in dopaminergic neurons during normal aging, and in Parkinson's disease, neurons with this pigment are those that selectively degenerate. Intraneuronal neuromelanin could play a protective role during its synthesis by preventing the toxic accumulation of cytosolic catechol derivatives and, in addition, by its ability to scavenge reactive metals, pesticides and other toxins to form stable adducts. However, dying neurons in Parkinson's disease that release neuromelanin might induce a vicious cycle of chronic neuroinflammation and neuronal loss.
View Article and Find Full Text PDFIt has been suggested that microglial inflammation augments the progression of Parkinson's disease (PD). However, endogenous factors initiating microglial activation are largely unknown. We therefore investigated the effects of human neuromelanin (NM) on the release of neurotoxic mediators and the underlying signaling pathways from rat microglia in vitro.
View Article and Find Full Text PDFBackground And Purpose: The present study was undertaken to determine the frequency of use of the ultrasound contrast agent (UCA) Levovist in routine transcranial ultrasound (TU). Additionally, we evaluated the diagnostic validity of contrast-enhanced TU using 3-dimensional time of flight MR angiography.
Methods: Indication for the UCA was an insufficient evaluation of the intracranial arteries after a combined approach with transcranial color-coded Duplex and transcranial Doppler examination.