Nadine Wilczak

Bio: Nadine Wilczak is an academic researcher from University Medical Center Groningen. The author has contributed to research in topics: Multiple sclerosis & Receptor. The author has an hindex of 23, co-authored 44 publications receiving 1467 citations. Previous affiliations of Nadine Wilczak include University of Groningen.

GFAP and S100B in the acute phase of mild traumatic brain injury

Abstract: Objective: The biomarkers glial fibrillary acid protein (GFAP) and S100B are increasingly used as prognostic tools in severe traumatic brain injury (TBI). Data for mild TBI are scarce. This study aims to analyze the predictive value of GFAP and S100B for outcome in mild TBI and the relation with imaging. Methods: In 94 patients biomarkers were determined directly after admission. Collected data included injury severity, patient characteristics, admission CT, and MRI 3 months postinjury. Six months postinjury outcome was determined with Glasgow Outcome Scale Extended (GOSE) and return to work (RTW). Results: Mean GFAP was 0.25 μg/L (SD 1.08) and S100B 0.54 μg/L (SD 1.18). In 63% GFAP was not discernible. GFAP was increased in patients with an abnormal CT (1.20 μg/L, SD 2.65) compared to normal CT (0.05 μg/L, SD 0.17, p p p Conclusions: A relation between GFAP with imaging studies and outcome (determined by RTW) was found in contrast to S100B. As the positive predictive value of GFAP is limited in this category of TBI patients, this biomarker is not suitable for prediction of individual patient outcome.

Astrocytes in multiple sclerosis lack beta-2 adrenergic receptors

Abstract: Background: In MS, T cells reactive to myelin proteins can cross the blood–brain barrier and release proinflammatory cytokines, such as interferon γ. These can induce glial cells to express class II major histocompatibility complex (MHC) molecules, which are required to present myelin antigens to the T cells in order to mount a proper autoimmune response. Both microglia and astrocytes can function as antigen-presenting cells. In contrast to microglia, endogenous suppressors, including norepinephrine, regulate astrocytic class II MHC expression. The effects of norepinephrine are mediated through activation of β 2 adrenergic receptors. Objective: To investigate β 2 adrenergic receptors in astrocytes in MS. Methods: Immunocytochemical techniques were applied in postmortem brain tissue from 10 patients with MS, three patients with a cerebral infarction, and six controls, and in spinal cord from three patients with ALS. Results: β 2 adrenergic receptors were visualized on astrocytes in white matter of controls, and they were prominently expressed in reactive astrocytes at the boundary of cerebral infarctions and in the lateral corticospinal tract in ALS. In MS, β 2 adrenergic receptors could neither be visualized on astrocytes in normal-appearing white matter nor in reactive astrocytes in chronic active and inactive plaques, whereas they were normally present on neurons. MHC class II–positive astrocytes were only visualized in chronic active plaques. Conclusions: Because astrocytic β 2 adrenergic receptors are involved in suppressing inducibility of MHC class II molecules, we suggest that their lack of expression may play an important role in the induction or perpetuation of autoimmune reactions in MS.

Insulin-like Growth Factor System Regulates Oligodendroglial Cell Behavior: Therapeutic Potential in CNS

Abstract: Amongst the many soluble extracellular factors stimulating intracellular signal transduction pathways and driving cellular processes such as proliferation, differentiation and survival, insulin-like growth factors (IGFs) stand out as indispensable factors for proper oligodendrocyte differentiation and accompanying myelin production. Owing to its potent myelinogenic capacity and its neuroprotective properties, IGFs hold therapeutic potential in demyelinating and neurodengenerative diseases. However, the IGF system is comprised of a complex molecular network involving regulatory binding proteins, proteases, cell surface and extracellular matrix components which orchestrate IGF-specific functions. Thus, the complexity by which these factors are tightly regulated makes a simplistic therapeutic approach towards treating demyelinating conditions unfeasible. In the present review, we address these issues and consider current therapeutic prospects of oligodendrocyte-targeted IGF-based therapies.

Principles of Neural Science

Abstract: I have developed "tennis elbow" from lugging this book around the past four weeks, but it is worth the pain, the effort, and the aspirin. It is also worth the (relatively speaking) bargain price. Including appendixes, this book contains 894 pages of text. The entire panorama of the neural sciences is surveyed and examined, and it is comprehensive in its scope, from genomes to social behaviors. The editors explicitly state that the book is designed as "an introductory text for students of biology, behavior, and medicine," but it is hard to imagine any audience, interested in any fragment of neuroscience at any level of sophistication, that would not enjoy this book. The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or

Remyelination in the CNS: from biology to therapy

Abstract: Remyelination involves reinvesting demyelinated axons with new myelin sheaths. In stark contrast to the situation that follows loss of neurons or axonal damage, remyelination in the CNS can be a highly effective regenerative process. It is mediated by a population of precursor cells called oligodendrocyte precursor cells (OPCs), which are widely distributed throughout the adult CNS. However, despite its efficiency in experimental models and in some clinical diseases, remyelination is often inadequate in demyelinating diseases such as multiple sclerosis (MS), the most common demyelinating disease and a cause of neurological disability in young adults. The failure of remyelination has profound consequences for the health of axons, the progressive and irreversible loss of which accounts for the progressive nature of these diseases. The mechanisms of remyelination therefore provide critical clues for regeneration biologists that help them to determine why remyelination fails in MS and in other demyelinating diseases and how it might be enhanced therapeutically.

Ageing and neuronal vulnerability

Abstract: Everyone ages, but only some will develop a neurodegenerative disorder in the process. Disease might occur when cells fail to respond adaptively to age-related increases in oxidative, metabolic and ionic stress, thereby resulting in the accumulation of damaged proteins, DNA and membranes. Determinants of neuronal vulnerability might include cell size and location, metabolism of disease-specific proteins and a repertoire of signal transduction pathways and stress resistance mechanisms. Emerging evidence on protein interaction networks that monitor and respond to the normal ageing process suggests that successful neural ageing is possible for most people, but also cautions that cures for neurodegenerative disorders are unlikely in the near future.

Alzheimer's Disease is Type 3 Diabetes—Evidence Reviewed

Abstract: Alzheimer's disease (AD) has characteristic histopathological, molecular, and biochemical abnormalities, including cell loss; abundant neurofibrillary tangles; dystrophic neurites; amyloid precursor protein, amyloid-β (APP-Aβ) deposits; increased activation of prodeath genes and signaling pathways; impaired energy metabolism; mitochondrial dysfunction; chronic oxidative stress; and DNA damage. Gaining a better understanding of AD pathogenesis will require a framework that mechanistically interlinks all these phenomena. Currently, there is a rapid growth in the literature pointing toward insulin deficiency and insulin resistance as mediators of AD-type neurodegeneration, but this surge of new information is riddled with conflicting and unresolved concepts regarding the potential contributions of type 2 diabetes mellitus (T2DM), metabolic syndrome, and obesity to AD pathogenesis. Herein, we review the evidence that (1) T2DM causes brain insulin resistance, oxidative stress, and cognitive impairment, but its aggregate effects fall far short of mimicking AD; (2) extensive disturbances in brain insulin and insulin-like growth factor (IGF) signaling mechanisms represent early and progressive abnormalities and could account for the majority of molecular, biochemical, and histopathological lesions in AD; (3) experimental brain diabetes produced by intracerebral administration of streptozotocin shares many features with AD, including cognitive impairment and disturbances in acetylcholine homeostasis; and (4) experimental brain diabetes is treatable with insulin sensitizer agents, i.e., drugs currently used to treat T2DM. We conclude that the term “type 3 diabetes” accurately reflects the fact that AD represents a form of diabetes that selectively involves the brain and has molecular and biochemical features that overlap with both type 1 diabetes mellitus and T2DM.