Gliomas and the vascular fragility of the blood brain barrier

Astrocytes, members of the glial family, interact through the exchange of soluble factors or by directly contacting neurons and other brain cells, such as microglia and endothelial cells. Astrocytic projections interact with vessels and act as additional elements of the Blood Brain Barrier (BBB). By mechanisms not fully understood, astrocytes can undergo oncogenic transformation and give rise to gliomas. The tumors take advantage of the BBB to ensure survival and continuous growth. A glioma can develop into a very aggressive tumor, the glioblastoma (GBM), characterized by a highly heterogeneous cell population (including tumor stem cells), extensive proliferation and migration. Nevertheless, gliomas can also give rise to slow growing tumors and in both cases, the afflux of blood, via BBB is crucial. Glioma cells migrate to different regions of the brain guided by the extension of blood vessels, colonizing the healthy adjacent tissue. In the clinical context, GBM can lead to tumor-derived seizures, which represent a challenge to patients and clinicians, since drugs used for its treatment must be able to cross the BBB. Uncontrolled and fast growth also leads to the disruption of the chimeric and fragile vessels in the tumor mass resulting in peritumoral edema. Although hormonal therapy is currently used to control the edema, it is not always efficient. In this review we comment the points cited above, considering the importance of the BBB and the concerns that arise when this barrier is affected.

[1]  H. Sontheimer,et al.  Expression and function of water channels (aquaporins) in migrating malignant astrocytes , 2007, Glia.

[2]  Hyun Seok Song,et al.  SSeCKS regulates angiogenesis and tight junction formation in blood-brain barrier , 2003, Nature Medicine.

[3]  D. Louis WHO classification of tumours of the central nervous system , 2007 .

[4]  M. Preusser,et al.  Circulating biomarkers of CNS tumors: an update. , 2013, Biomarkers in medicine.

[5]  M. Field,et al.  The Effects of Histone Deacetylase Inhibitors on Glioblastoma-Derived Stem Cells , 2014, Journal of Molecular Neuroscience.

[6]  Thomas Brinker,et al.  Multiplicity of cerebrospinal fluid functions: New challenges in health and disease , 2008, Cerebrospinal Fluid Research.

[7]  Luciana Romão,et al.  Glioblastoma: therapeutic challenges, what lies ahead. , 2012, Biochimica et biophysica acta.

[8]  R. Janzer,et al.  Astrocytes induce blood–brain barrier properties in endothelial cells , 1987, Nature.

[9]  H. Wolburg,et al.  An Allograft Glioma Model Reveals the Dependence of Aquaporin-4 Expression on the Brain Microenvironment , 2012, PloS one.

[10]  Helios Klinikum The Antitumorigenic Response of Neural Precursors Depends on Subventricular Proliferation and Age , 2008 .

[11]  E. Kroh,et al.  Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma , 2011, Proceedings of the National Academy of Sciences.

[12]  B. Barres,et al.  Pericytes are required for blood–brain barrier integrity during embryogenesis , 2010, Nature.

[13]  J. Duncan,et al.  The choroid plexus-cerebrospinal fluid system: from development to aging. , 2005, Current topics in developmental biology.

[14]  N. Kosaka,et al.  Unraveling the Mystery of Cancer by Secretory microRNA: Horizontal microRNA Transfer between Living Cells , 2011, Front. Gene..

[15]  Becky,et al.  Dexamethasone-induced abolition of the inflammatory response in an experimental glioma model: a flow cytometry study. , 2000, Journal of neurosurgery.

[16]  N. B. Viana,et al.  Tenascin-C in the extracellular matrix promotes the selection of highly proliferative and tubulogenesis-defective endothelial cells. , 2011, Experimental cell research.

[17]  M. Perretti,et al.  Regulation of Leukocyte‐Endothelial Interactions by Glucocorticoids , 2002, Annals of the New York Academy of Sciences.

[18]  H. Galla,et al.  Control of the Blood–Brain Barrier by Glucocorticoids and the Cells of the Neurovascular Unit , 2009, Annals of the New York Academy of Sciences.

[19]  J. Michálek,et al.  MicroRNAs and glioblastoma: roles in core signalling pathways and potential clinical implications , 2011, Journal of cellular and molecular medicine.

[20]  R. Spector Nature and consequences of mammalian brain and CSF efflux transporters: four decades of progress , 2010, Journal of neurochemistry.

[21]  M. C. Papadopoulos,et al.  Molecular mechanisms of brain tumor edema , 2004, Neuroscience.

[22]  Frans S S Leijten,et al.  Electrocorticographic Discharge Patterns in Glioneuronal Tumors and Focal Cortical Dysplasia , 2006, Epilepsia.

[23]  A. Meister,et al.  [30] γ-Glutamyl transpeptidase , 1981 .

[24]  J. Barnholtz-Sloan,et al.  CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2007-2011. , 2012, Neuro-oncology.

[25]  R. Panizzutti,et al.  Astrocyte-induced Synaptogenesis Is Mediated by Transforming Growth Factor β Signaling through Modulation of d-Serine Levels in Cerebral Cortex Neurons* , 2012, The Journal of Biological Chemistry.

[26]  Benjamin Purow,et al.  The elephant in the room: do microRNA-based therapies have a realistic chance of succeeding for brain tumors such as glioblastoma? , 2011, Journal of Neuro-Oncology.

[27]  B. Scheithauer,et al.  The 2007 WHO classification of tumours of the central nervous system , 2007, Acta Neuropathologica.

[28]  Jan Claassen,et al.  Treatment of status epilepticus: a survey of neurologists , 2003, Journal of the Neurological Sciences.

[29]  P. Kelly,et al.  Grading of astrocytomas: A simple and reproducible method , 1988, Cancer.

[30]  S. Pastorino,et al.  MicroRNAs in cerebrospinal fluid identify glioblastoma and metastatic brain cancers and reflect disease activity. , 2012, Neuro-oncology.

[31]  K. P. Lehre,et al.  The perivascular astroglial sheath provides a complete covering of the brain microvessels: An electron microscopic 3D reconstruction , 2010, Glia.

[32]  A. Hirano,et al.  Vascular structures in brain tumors. , 1975, Human pathology.

[33]  Mitchel S Berger,et al.  Seizure characteristics and control following resection in 332 patients with low-grade gliomas. , 2008, Journal of neurosurgery.

[34]  T. Ochiya,et al.  The Impact of Extracellular Vesicle-Encapsulated Circulating MicroRNAs in Lung Cancer Research , 2014, BioMed research international.

[35]  Y. Hayashi,et al.  Regulation and function of aquaporin-1 in glioma cells. , 2007, Neoplasia.

[36]  T. Hander,et al.  A phase I trial of human corticotropin-releasing factor (hCRF) in patients with peritumoral brain edema. , 1998, Annals of oncology : official journal of the European Society for Medical Oncology.

[37]  Peter Agre,et al.  Aquaporin Water Channels , 2004, Proceedings of the American Thoracic Society.

[38]  G. Reid,et al.  Cell-free microRNAs: potential biomarkers in need of standardized reporting , 2013, Front. Genet..

[39]  L. Svennerholm Molecular neuropathology. , 1976, Progress in brain research.

[40]  K. Vickers,et al.  MicroRNAs are Transported in Plasma and Delivered to Recipient Cells by High-Density Lipoproteins , 2011, Nature Cell Biology.

[41]  Daniel H. Geschwind,et al.  Cancerous stem cells can arise from pediatric brain tumors , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[42]  Jing Liu,et al.  Potential of cancer cell-derived exosomes in clinical application: a review of recent research advances. , 2014, Clinical therapeutics.

[43]  X. Breakefield,et al.  Brain Tumor Microvesicles: Insights into Intercellular Communication in the Nervous System , 2011, Cellular and Molecular Neurobiology.

[44]  S. Kahn,et al.  Microglial stress inducible protein 1 promotes proliferation and migration in human glioblastoma cells , 2012, Neuroscience.

[45]  Shanquan Sun,et al.  Expression of aquaporin8 in human astrocytomas: correlation with pathologic grade. , 2013, Biochemical and biophysical research communications.

[46]  M. Bastin,et al.  Effects of dexamethasone on peritumoural oedematous brain: a DT-MRI study , 2004, Journal of Neurology, Neurosurgery & Psychiatry.

[47]  Barbara Burwinkel,et al.  Extracellular miRNAs: the mystery of their origin and function. , 2012, Trends in biochemical sciences.

[48]  Hilla Peretz,et al.  Ju n 20 03 Schrödinger ’ s Cat : The rules of engagement , 2003 .

[49]  R. Ransohoff,et al.  Development, maintenance and disruption of the blood-brain barrier , 2013, Nature Medicine.

[50]  L. Qin,et al.  The molecular mechanism of dexamethasone-mediated effect on the blood–brain tumor barrier permeability in a rat brain tumor model , 2009, Neuroscience Letters.

[51]  T. Vats,et al.  Targeted Brain Tumor Treatment-Current Perspectives , 2007, Drug target insights.

[52]  C. Iadecola Neurovascular regulation in the normal brain and in Alzheimer's disease , 2004, Nature Reviews Neuroscience.

[53]  E. Avignone,et al.  Gap junctions and connexin expression in the normal and pathological central nervous system , 2002, Biology of the cell.

[54]  H. Reulen,et al.  A computed tomography study on formation, propagation, and resolution of edema fluid in metastatic brain tumors. , 1990, Advances in neurology.

[55]  Xi Chen,et al.  Identification of seven serum microRNAs from a genome‐wide serum microRNA expression profile as potential noninvasive biomarkers for malignant astrocytomas , 2013, International journal of cancer.

[56]  P. Rakic,et al.  Role of GGF/neuregulin signaling in interactions between migrating neurons and radial glia in the developing cerebral cortex. , 1997, Development.

[57]  K. Kristensson,et al.  Tryps and trips: cell trafficking across the 100-year-old blood–brain barrier , 2014, Trends in Neurosciences.

[58]  E. Maiorano,et al.  Ultrastructural and morphometric investigation of human brain capillaries in normal and peritumoral tissues. , 1997, Ultrastructural pathology.

[59]  John A Butman,et al.  Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[60]  Hamid Cheshmi Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers , 2011 .

[61]  M. Papadopoulos,et al.  Aquaporin water channels in the nervous system , 2013, Nature Reviews Neuroscience.

[62]  George C. Ebers,et al.  The natural history of multiple sclerosis, a geographically based study 10: relapses and long-term disability , 2010, Brain : a journal of neurology.

[63]  H. Dvorak,et al.  Rous-Whipple Award Lecture. How tumors make bad blood vessels and stroma. , 2003, The American journal of pathology.

[64]  C. Iadecola,et al.  Glial regulation of the cerebral microvasculature , 2007, Nature Neuroscience.

[65]  R. Holmes,et al.  p-(Chloromercuri)benzenesulfonate binding by membrane proteins and the inhibition of water transport in human erythrocytes. , 1986, Biochemistry.

[66]  A. Vorbrodt,et al.  Molecular anatomy of intercellular junctions in brain endothelial and epithelial barriers: electron microscopist’s view , 2003, Brain Research Reviews.

[67]  M. Rauh,et al.  Dexamethasone Alleviates Tumor-Associated Brain Damage and Angiogenesis , 2014, PloS one.

[68]  J. Antel,et al.  Glial cell influence on the human blood‐brain barrier , 2001, Glia.

[69]  R. Jain,et al.  VEGF inhibitors in the treatment of cerebral edema in patients with brain cancer , 2009, Nature Reviews Clinical Oncology.

[70]  N. Chaverot,et al.  Molecular Mechanism of Systemic Delivery of Neural Precursor Cells to the Brain: Assembly of Brain Endothelial Apical Cups and Control of Transmigration by CD44 , 2008, Stem cells.

[71]  V. M. Neto,et al.  Cerebellar astrocytes treated by thyroid hormone modulate neuronal proliferation , 1999, Glia.

[72]  M. Wood,et al.  Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes , 2011, Nature Biotechnology.

[73]  Abdelouahid Maghnouj,et al.  Identification of microRNAs in the cerebrospinal fluid as biomarker for the diagnosis of glioma. , 2012, Neuro-oncology.

[74]  S. Liebner,et al.  Claudin-1 and claudin-5 expression and tight junction morphology are altered in blood vessels of human glioblastoma multiforme , 2000, Acta Neuropathologica.

[75]  A. Maslov,et al.  Neural Stem Cell Detection, Characterization, and Age- Related Changes in the Subventricular Zone of Mice , 2022 .

[76]  F. Pfrieger,et al.  Synaptic efficacy enhanced by glial cells in vitro. , 1997, Science.

[77]  R. Keep,et al.  A morphometric study on the development of the lateral ventricle choroid plexus, choroid plexus capillaries and ventricular ependyma in the rat. , 1990, Brain research. Developmental brain research.

[78]  H. Kettenmann,et al.  Bone morphogenetic protein-7 release from endogenous neural precursor cells suppresses the tumourigenicity of stem-like glioblastoma cells. , 2010, Brain : a journal of neurology.

[79]  J. Lötvall,et al.  Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells , 2007, Nature Cell Biology.

[80]  C. Kruchko,et al.  CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2005-2009. , 2012, Neuro-oncology.

[81]  W. Lukiw,et al.  microRNA (miRNA) speciation in Alzheimer's disease (AD) cerebrospinal fluid (CSF) and extracellular fluid (ECF). , 2012, International journal of biochemistry and molecular biology.

[82]  M. Mizoguchi,et al.  Clinical implications of microRNAs in human glioblastoma , 2013, Front. Oncol..

[83]  A. Álvarez-Buylla,et al.  Interaction between astrocytes and adult subventricular zone precursors stimulates neurogenesis. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[84]  Nathan McDannold,et al.  Ultrasound-mediated blood-brain barrier disruption for targeted drug delivery in the central nervous system. , 2014, Advanced drug delivery reviews.

[85]  T. Kielian Glial connexins and gap junctions in CNS inflammation and disease , 2008, Journal of neurochemistry.

[86]  S. Schwartz,et al.  Efficient intracellular delivery of siRNA with a safe multitargeted lipid-based nanoplatform. , 2013, Nanomedicine.

[87]  S. Berntsson,et al.  Epileptic seizures and survival in early disease of grade 2 gliomas , 2009, European journal of neurology.

[88]  C. Miller,et al.  Glioblastoma: Morphologic and molecular genetic diversity , 2007 .

[89]  Robert C. Rostomily,et al.  The cause of death in patients with glioblastoma is multifactorial: , 1991, Journal of Neuro-Oncology.

[90]  I. R. Whittle,et al.  The Pathogenesis of Tumour Associated Epilepsy , 2000, Acta Neurochirurgica.

[91]  David J. Begley,et al.  Structure and function of the blood–brain barrier , 2010, Neurobiology of Disease.

[92]  J. Segovia,et al.  Transmigration of Neural Stem Cells across the Blood Brain Barrier Induced by Glioma Cells , 2013, PloS one.

[93]  E. Hedley‐Whyte,et al.  Effect of dexamethasone on blood-brain barrier in the normal mouse. , 1986, Annals of neurology.

[94]  S. Rosalki Gamma-glutamyl transpeptidase. , 1975, Advances in clinical chemistry.

[95]  E. Olson,et al.  Toward microRNA-based therapeutics for heart disease: the sense in antisense. , 2008, Circulation research.

[96]  C. Yun,et al.  Levetiracetam Compared with Valproic Acid for the Prevention of Postoperative Seizures After Supratentorial Tumor Surgery: A Retrospective Chart Review , 2013, CNS Drugs.

[97]  M. Taphoorn,et al.  Effect of valproic acid on seizure control and on survival in patients with glioblastoma multiforme. , 2013, Neuro-oncology.

[98]  C. Nimsky,et al.  Small interfering RNA–mediated xCT silencing in gliomas inhibits neurodegeneration and alleviates brain edema , 2008, Nature Medicine.

[99]  E. Goldmann Die äussere und innere Sekretion des gesunden Organismus im Lichte der "vitalen Färbung" , 1909 .

[100]  H. Kim,et al.  Dexamethasone coordinately regulates angiopoietin-1 and VEGF: a mechanism of glucocorticoid-induced stabilization of blood-brain barrier. , 2008, Biochemical and biophysical research communications.

[101]  Shinobu Ueda,et al.  Systemically Injected Exosomes Targeted to EGFR Deliver Antitumor MicroRNA to Breast Cancer Cells. , 2013, Molecular therapy : the journal of the American Society of Gene Therapy.

[102]  M. Hristov,et al.  Delivery of MicroRNA-126 by Apoptotic Bodies Induces CXCL12-Dependent Vascular Protection , 2009, Science Signaling.

[103]  Gilberto Alves,et al.  Blood-brain barrier models and their relevance for a successful development of CNS drug delivery systems: a review. , 2014, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[104]  E. Keshet,et al.  Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis , 1992, Nature.

[105]  K. Kim,et al.  Human astrocytes/astrocyte-conditioned medium and shear stress enhance the barrier properties of human brain microvascular endothelial cells , 2007, Brain Research.

[106]  E. Hedley‐Whyte,et al.  Effect of dexamethasone on blood‐brain barrier in the normal mouse , 1986, Annals of neurology.

[107]  M. C. Angulo,et al.  Neuron-to-astrocyte signaling is central to the dynamic control of brain microcirculation , 2003, Nature Neuroscience.

[108]  Graça Raposo,et al.  Extracellular vesicles: Exosomes, microvesicles, and friends , 2013, The Journal of cell biology.

[109]  J. Melby,et al.  Use of dexamethasone in treatment of cerebral edema associated with brain tumors. , 1961, The Journal-lancet.

[110]  C. Hess,et al.  Dexamethasone treatment in patients with brain metastases and primary brain tumors: do the benefits outweigh the side-effects? , 2002, Supportive Care in Cancer.

[111]  B. Knight The Cause of Death , 1986, Journal of the Royal Society of Medicine.

[112]  S. Booth,et al.  Corticosteroid-use in primary and secondary brain tumour patients: a review , 2012, Journal of Neuro-Oncology.

[113]  M. Deli Blood-brain barrier models , 2007 .

[114]  Ralph Weissleder,et al.  In vivo tracking of neural progenitor cell migration to glioblastomas. , 2003, Human gene therapy.

[115]  I. Blasig,et al.  In Search of the Astrocytic Factor(s) Modulating Blood–Brain Barrier Functions in Brain Capillary Endothelial Cells In Vitro , 2005, Cellular and Molecular Neurobiology.

[116]  S. Rüegg,et al.  Brain Tumor and Seizures: Pathophysiology and Its Implications for Treatment Revisited , 2003, Epilepsia.

[117]  Helena Borges,et al.  Glioblastoma cells: a heterogeneous and fatal tumor interacting with the parenchyma. , 2011, Life sciences.

[118]  V. M. Neto,et al.  Neuro–glia interaction effects on GFAP gene: a novel role for transforming growth factor‐β1 , 2002, The European journal of neuroscience.

[119]  K. Ishibashi,et al.  [Aquaporin water channels]. , 1996, Nihon rinsho. Japanese journal of clinical medicine.

[120]  Dongmei Sun,et al.  Treatment of brain inflammatory diseases by delivering exosome encapsulated anti-inflammatory drugs from the nasal region to the brain. , 2011, Molecular therapy : the journal of the American Society of Gene Therapy.

[121]  E. Hansson,et al.  Astrocyte–endothelial interactions at the blood–brain barrier , 2006, Nature Reviews Neuroscience.

[122]  N. Abbott Blood–brain barrier structure and function and the challenges for CNS drug delivery , 2013, Journal of Inherited Metabolic Disease.

[123]  C. B. Trites Epileptic seizures. , 1951, Canadian Medical Association journal.

[124]  Hui Zhou,et al.  MicroRNA-195 plays a tumor-suppressor role in human glioblastoma cells by targeting signaling pathways involved in cellular proliferation and invasion. , 2012, Neuro-oncology.

[125]  F. Tovar-Moll,et al.  Equinatoxin II potentiates temozolomide- and etoposide-induced glioblastoma cell death. , 2012, Current topics in medicinal chemistry.

[126]  H. Kettenmann,et al.  Tumor Young Investigator Award: tropism and antitumorigenic effect of endogenous neural precursors for gliomas. , 2006, Clinical neurosurgery.

[127]  P. Keegan,et al.  FDA drug approval summary: bevacizumab (Avastin) as treatment of recurrent glioblastoma multiforme. , 2009, The oncologist.

[128]  E. Goldmann Neue Untersuchungen über die äussere und innere Sekretion des gesunden und kranken Organismus im Lichte der"vitalen Färbung" , 1912 .

[129]  M. Gassmann,et al.  Astrocytes and Pericytes Differentially Modulate Blood—Brain Barrier Characteristics during Development and Hypoxic Insult , 2011, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[130]  P. Black,et al.  Neural stem cells display extensive tropism for pathology in adult brain: evidence from intracranial gliomas. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[131]  Alan J. Wilson,et al.  The blood-brain barrier: an important concept in neuroimaging. , 1994, AJNR. American journal of neuroradiology.

[132]  E. Papavassiliou,et al.  Mechanism of dexamethasone suppression of brain tumor-associated vascular permeability in rats. Involvement of the glucocorticoid receptor and vascular permeability factor. , 1996, The Journal of clinical investigation.

[133]  T. Mikkelsen,et al.  Corticosteroid use in patients with glioblastoma at first or second relapse treated with bevacizumab in the BRAIN study. , 2010, The oncologist.

[134]  H. Lassmann,et al.  Microglial cells are a component of the perivascular glia limitans , 1991, Journal of neuroscience research.

[135]  Takahiro Ochiya,et al.  Circulating microRNA in body fluid: a new potential biomarker for cancer diagnosis and prognosis , 2010, Cancer science.

[136]  Graça Raposo,et al.  Exosomes--vesicular carriers for intercellular communication. , 2009, Current opinion in cell biology.

[137]  Alon Friedman,et al.  TGF-beta receptor-mediated albumin uptake into astrocytes is involved in neocortical epileptogenesis. , 2007, Brain : a journal of neurology.

[138]  S. Strother,et al.  The time course of steroid action on blood‐to‐brain and blood‐to‐tumor transport of 82Rb: A positron emission tomographic study , 1989, Annals of neurology.

[139]  R. Michelucci,et al.  Epilepsy in primary cerebral tumors: The characteristics of epilepsy at the onset (results from the PERNO study – Project of Emilia Romagna Region on Neuro‐Oncology) , 2013, Epilepsia.

[140]  P. Cahill,et al.  Influence of basolateral condition on the regulation of brain microvascular endothelial tight junction properties and barrier function , 2008, Brain Research.

[141]  T. Takano,et al.  Astrocyte-mediated control of cerebral blood flow , 2006, Nature Neuroscience.

[142]  E. Mason Cause of Death , 2007, Obesity surgery.

[143]  Bethan Hughes,et al.  2008 FDA drug approvals , 2009, Nature Reviews Drug Discovery.

[144]  C. Vecht,et al.  Seizure prognosis in brain tumors: new insights and evidence-based management. , 2014, The oncologist.

[145]  Suzana Herculano-Houzel,et al.  The glia/neuron ratio: How it varies uniformly across brain structures and species and what that means for brain physiology and evolution , 2014, Glia.

[146]  A. Vezzani,et al.  Brain Inflammation in Epilepsy: Experimental and Clinical Evidence , 2005, Epilepsia.

[147]  B. Barres,et al.  Induction of Astrocyte Differentiation by Endothelial Cells , 2001, The Journal of Neuroscience.

[148]  P. Cancilla,et al.  gamma-Glutamyl transpeptidase in isolated brain endothelial cells: induction by glial cells in vitro. , 1980, Science.

[149]  U. Gimsa,et al.  Immune Privilege as an Intrinsic CNS Property: Astrocytes Protect the CNS against T-Cell-Mediated Neuroinflammation , 2013, Mediators of inflammation.

[150]  G. Reifenberger,et al.  Molecular Neuropathology of Gliomas , 2009, International journal of molecular sciences.

[151]  H. Kettenmann,et al.  Glioblastoma-Induced Attraction of Endogenous Neural Precursor Cells Is Associated with Improved Survival , 2005, The Journal of Neuroscience.

[152]  Hiroshi Yamamoto,et al.  Induction of various blood‐brain barrier properties in non‐neural endothelial cells by close apposition to co‐cultured astrocytes , 1997, Glia.

[153]  L. Wilkins The Epileptic Seizure , 1958, Neurology.

[154]  T. Yamashita,et al.  Molecular Therapeutic Targets for Glioma Angiogenesis , 2010, Journal of oncology.

[155]  B. Kolls,et al.  Phenytoin, Levetiracetam, and Pregabalin in the Acute Management of Refractory Status Epilepticus in Patients with Brain Tumors , 2012, Neurocritical Care.

[156]  Maria K. Lehtinen,et al.  The Cerebrospinal Fluid Provides a Proliferative Niche for Neural Progenitor Cells , 2011, Neuron.

[157]  David N Louis,et al.  Molecular pathology of malignant gliomas. , 2006, Annual review of pathology.

[158]  N. Wu,et al.  Circulating MicroRNAs: A Novel Class of Potential Biomarkers for Diagnosing and Prognosing Central Nervous System Diseases , 2013, Cellular and Molecular Neurobiology.

[159]  S. Simões,et al.  Design of peptide-targeted liposomes containing nucleic acids. , 2010, Biochimica et biophysica acta.