Mechanisms of Post-hemorrhagic Hydrocephalus after Germinal Matrix Hemorrhage

The inherently fragile vasculature of the germinal matrix is susceptible to rupture, possibly as a result of hemodynamic and cardiorespiratory instability associated with prematurity. Germinal matrix hemorrhage is a leading cause of morbidity and mortality in preterm and/or very low birthweight infants, and post-hemorrhagic hydrocephalus is major consequence of severe grade hemorrhages. Chronic post-hemorrhagic hydrocephalus treatment involves surgical insertion of shunts, which are costly and prone to complications. Thus, a safe non-invasive therapeutic approach towards post-hemorrhagic hydrocephalus clinical management would significantly improve the quality of life for this patient population. Thrombin, cerebroventricular blood clots, and iron have been identified as causative factors of hydrocephalus formation. Thrombin stimulates proteinase-activated receptors, leading to subsequent mTOR activation and extracellular matrix protein proliferation, which possibly obstruct the cerebroventricular system. Blood clots may directly impair cerebrospinal fluid circulation and absorption. PPARγ stimulation enhances micgroglial/macrophage phagocytosis of erythrocytes via CD36 scavenger receptor, augmenting clot resolution and improving outcomes after adult cerebral hemorrhage. Additionally, lysed erythrocytes and metabolized hemoglobin release iron, which is associated with brain injury after adult cerebral hemorrhage and contribute to post-hemorrhagic hydrocephalus development. The central aim of this proposal is to determine the role of activated thrombin/PAR-1/mTOR pathway as well as the role of hematoma resolution by PPARγ/CD36 and iron chelation by Deferoxamine in hydrocephalus development after germinal matrix hemorrhage. Direct thrombin inhibition reduced short-term mTOR activation and ameliorated long-term post-hemorrhagic hydrocephalus development, neurocogntive deficits, and extracellular matrix protein proliferation, although PAR-1 inhibition alone did not achieve the same therapeutic benefits. PPARγ stimulation improved short-term hematoma resolution, which was reversed by PPARγ antagonism and CD36 knockdown. PPARγ stimulation attenuated long-term neurocognitive deficits and post-hemorrhagic hydrocephalus, which was reversed by PPARγ antagonism. Acute and delayed iron chelation also reduced long-term post-hemorrhagic hydrocephalus development, neurocognitive deficits, and extracellular matrix protein proliferation. Thus, thrombin/PAR/mTOR pathway inhibition, enhanced PPARγ/CD36 mediated hematoma resolution, and iron chelation significantly ameliorated short and long-term brain sequelae after germinal matrix hemorrhage and are clinically viable therapeutic targets warranting further investigation

Central Nervous System Tumors

Though the treatment of central nervous system (CNS) tumors has been challenging, new advances have helped us better understand the molecular and genetic makeup of many tumor types, and new chemotherapies and immunotherapies have extended survival in patients with aggressive primary CNS tumors. This book discusses pediatric and adult tumors of the CNS, the classification schemes used to categorize them, advances in surgical techniques, and several important genetic alterations found in these tumors. We hope this book contributes to the reader’s understanding of these tumors and provides the most up-to-date and cutting-edge discoveries in this exciting field

Diseases of the Brain, Head and Neck, Spine 2020–2023

This open access book offers an essential overview of brain, head and neck, and spine imaging. Over the last few years, there have been considerable advances in this area, driven by both clinical and technological developments. Written by leading international experts and teachers, the chapters are disease-oriented and cover all relevant imaging modalities, with a focus on magnetic resonance imaging and computed tomography. The book also includes a synopsis of pediatric imaging. IDKD books are rewritten (not merely updated) every four years, which means they offer a comprehensive review of the state-of-the-art in imaging. The book is clearly structured and features learning objectives, abstracts, subheadings, tables and take-home points, supported by design elements to help readers navigate the text. It will particularly appeal to general radiologists, radiology residents, and interventional radiologists who want to update their diagnostic expertise, as well as clinicians from other specialties who are interested in imaging for their patient care

Definitions and classification of malformations of cortical development: Practical guidelines

Malformations of cortical development are a group of rare disorders commonly manifesting with developmental delay, cerebral palsy or seizures. The neurological outcome is extremely variable depending on the type, extent and severity of the malformation and the involved genetic pathways of brain development. Neuroimaging plays an essential role in the diagnosis of these malformations, but several issues regarding malformations of cortical development definitions and classification remain unclear. The purpose of this consensus statement is to provide standardized malformations of cortical development terminology and classification for neuroradiological pattern interpretation. A committee of international experts in paediatric neuroradiology prepared systematic literature reviews and formulated neuroimaging recommendations in collaboration with geneticists, paediatric neurologists and pathologists during consensus meetings in the context of the European Network Neuro-MIG initiative on Brain Malformations (https://www.neuro-mig.org/). Malformations of cortical development neuroimaging features and practical recommendations are provided to aid both expert and non-expert radiologists and neurologists who may encounter patients with malformations of cortical development in their practice, with the aim of improving malformations of cortical development diagnosis and imaging interpretation worldwide

Definitions and classification of malformations of cortical development: practical guidelines

Malformations of cortical development are a group of rare disorders commonly manifesting with developmental delay, cerebral palsy or seizures. The neurological outcome is extremely variable depending on the type, extent and severity of the malformation and the involved genetic pathways of brain development. Neuroimaging plays an essential role in the diagnosis of these malformations, but several issues regarding malformations of cortical development definitions and classification remain unclear. The purpose of this consensus statement is to provide standardized malformations of cortical development terminology and classification for neuroradiological pattern interpretation. A committee of international experts in paediatric neuroradiology prepared systematic literature reviews and formulated neuroimaging recommendations in collaboration with geneticists, paediatric neurologists and pathologists during consensus meetings in the context of the European Network Neuro-MIG initiative on Brain Malformations (https://www.neuro-mig.org/). Malformations of cortical development neuroimaging features and practical recommendations are provided to aid both expert and non-expert radiologists and neurologists who may encounter patients with malformations of cortical development in their practice, with the aim of improving malformations of cortical development diagnosis and imaging interpretation worldwide

Insight in the physiopathology of the developing brain: prenatal imaging and experimental models

This phD research line has been developed into 3 branches as follows: - the main part (A) focused on a specific aspect of the ventral induction and its failure: the developing cerebellum, with a special insight in the midline structures of the posterior fossa. This main part explores the diagnostic potentialities of prenatal imaging such as ultrasound and magnetic resonance imaging (MRI), which, thanks to the ongoing technical and scientific progress, have evolved from almost exclusively experimental examinations to clinically important tools, which impact decision making in the field of pre- and perinatal medicine; - the second part (B) has been dedicated to the prenatal ultrasonographic imaging of neuronal migration, with special attention to the growing fetal cortex, whose fissures and sulci mark progressively its development throughout gestation; - an ancillary part (C) has dealt with experimental translational stem cell research in acquired fetal brain injuries. This is a currently ongoing project, including in-vitro experiments as well as in- vivo-transplantation of stem cells and stem cell derivates for peripartum neuro-regeneration in an experimental model. Only the little contribution of this thesis to this ongoing project has here briefly reported

Current Frontiers and Perspectives in Cell Biology

A numerous internationally renowned authors in the pages of this book present the views of the fields of cell biology and their own research results or review of current knowledge. Chapters are divided into five sections that are dedicated to cell structures and functions, genetic material, regulatory mechanisms, cellular biomedicine and new methods in cell biology. Multidisciplinary and often quite versatile approach by many authors have imposed restrictions of this classification, so it is certain that many chapters could belong to the other sections of this book. The current frontiers, on the manner in which they described in the book, can be a good inspiration to many readers for further improving, and perspectives which are highlighted can be seen in many areas of fundamental biology, biomedicine, biotechnology and other applications of knowledge of cell biology. The book will be very useful for beginners to gain insight into new area, as well as experts to find new facts and expanding horizons