Blood–brain barrier and traumatic brain injury

The blood–brain barrier (BBB) is an anatomical microstructural unit, with several different components playing key roles in normal brain physiological regulation. Formed by tightly connected cerebrovascular endothelial cells, its normal function depends on paracrine interactions between endothelium and closely related glia, with several recent reports stressing the need to consider the entire gliovascular unit in order to explain the underlying cellular and molecular mechanisms. Despite that, with regard to traumatic brain injury (TBI) and significant events in incidence and potential clinical consequences in pediatric and adult ages, little is known about the actual role of BBB disruption in its diverse pathological pathways. This Mini‐Review addresses the current literature on possible factors affecting gliovascular units and contributing to posttraumatic BBB dysfunction, including neuroinflammation and disturbed transport mechanisms along with altered permeability and consequent posttraumatic edema. Key mechanisms and its components are described, and promising lines of basic and clinical research are identified, because further knowledge on BBB pathological interference should play a key role in understanding TBI and provide a basis for possible therapeutic targets in the near future, whether through restoration of normal BBB function after injury or delivering drugs in an increased permeability context, preventing secondary damage and improving functional outcome. © 2013 Wiley Periodicals, Inc.

[1]  H. Lassmann,et al.  The fibrin-derived γ377-395 peptide inhibits microglia activation and suppresses relapsing paralysis in central nervous system autoimmune disease , 2007, The Journal of experimental medicine.

[2]  C. Gyldensted,et al.  Blood Flow and Ischemia within Traumatic Cerebral Contusions , 2002, Neurosurgery.

[3]  Alon Friedman,et al.  Blood–brain barrier breakdown as a therapeutic target in traumatic brain injury , 2010, Nature Reviews Neurology.

[4]  Takahiro Doi,et al.  NF‐κB inhibits TNF‐induced accumulation of ROS that mediate prolonged MAPK activation and necrotic cell death , 2003, The EMBO journal.

[5]  M. Jouvet,et al.  Alteration in central and peripheral substance P- and neuropeptide Y-like immunoreactivity after chronic hypoxia in the rat , 1996, Brain Research.

[6]  T. L. Briones,et al.  Modulation of ischemia-induced NMDAR1 activation by environmental enrichment decreases oxidative damage. , 2011, Journal of neurotrauma.

[7]  A. Hazell,et al.  Excitotoxic mechanisms and the role of astrocytic glutamate transporters in traumatic brain injury , 2006, Neurochemistry International.

[8]  J. Montaner,et al.  Moderate and severe traumatic brain injury induce early overexpression of systemic and brain gelatinases , 2008, Intensive Care Medicine.

[9]  J. Neale,et al.  NAAG peptidase inhibitor increases dialysate NAAG and reduces glutamate, aspartate and GABA levels in the dorsal hippocampus following fluid percussion injury in the rat , 2006, Journal of neurochemistry.

[10]  B. Wiesner,et al.  Formation of tight junction: determinants of homophilic interaction between classic claudins , 2008, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[11]  R. Vink,et al.  Substance P is Associated with the Development of Brain Edema and Functional Deficits after Traumatic Brain Injury , 2009, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[12]  R. Vink,et al.  Substance P antagonists as a therapeutic approach to improving outcome following traumatic brain injury , 2011, Neurotherapeutics.

[13]  R. Vink,et al.  A substance P antagonist reduces axonal injury and improves neurologic outcome when administered up to 12 hours after traumatic brain injury. , 2011, Journal of neurotrauma.

[14]  G. Rosenberg Matrix metalloproteinases and their multiple roles in neurodegenerative diseases , 2009, The Lancet Neurology.

[15]  O. Alonso,et al.  Influence of Therapeutic Hypothermia on Matrix Metalloproteinase Activity after Traumatic Brain Injury in Rats , 2005, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[16]  W. D. Dietrich,et al.  Interleukin-1β Messenger Ribonucleic Acid and Protein Levels after Fluid-Percussion Brain Injury in Rats: Importance of Injury Severity and Brain Temperature. , 2002, Neurosurgery.

[17]  R. Vink,et al.  Substance P immunoreactivity increases following human traumatic brain injury. , 2010, Acta neurochirurgica. Supplement.

[18]  F. Joó,et al.  Expression of glutamate receptors on cultured cerebral endothelial cells , 1998, Journal of neuroscience research.

[19]  Guy C. Brown,et al.  Inflammatory Neurodegeneration and Mechanisms of Microglial Killing of Neurons , 2010, Molecular Neurobiology.

[20]  Jin Lei,et al.  Acute traumatic brain injury: is current management evidence based? An empirical analysis of systematic reviews. , 2013, Journal of neurotrauma.

[21]  M. Wendland,et al.  Blood–Brain Barrier Permeability Is Increased After Acute Adult Stroke But Not Neonatal Stroke in the Rat , 2012, The Journal of Neuroscience.

[22]  D. Miller,et al.  Tumor necrosis factor-alpha induces cyclooxygenase-2 expression and prostaglandin release in brain microvessel endothelial cells. , 2001, The Journal of pharmacology and experimental therapeutics.

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

[24]  D. Wong,et al.  Expression of vascular cell adhesion molecule-1 (VCAM-1) by human brain microvessel endothelial cells in primary culture. , 1995, Microvascular research.

[25]  J. Nutt,et al.  Strategies to advance translational research into brain barriers , 2008, The Lancet Neurology.

[26]  S. Lorenzl,et al.  Matrix metalloproteinases contribute to the blood—brain barrier disruption during bacterial meningitis , 1998, Annals of neurology.

[27]  J. Hillman,et al.  The cerebral extracellular release of glycerol, glutamate, and FGF2 is increased in older patients following severe traumatic brain injury. , 2012, Journal of neurotrauma.

[28]  Joseph R. Smith,et al.  ICAM-1 expression on human brain microvascular endothelial cells , 1994, Neuroscience Letters.

[29]  G. Rosenberg,et al.  Multiple roles for MMPs and TIMPs in cerebral ischemia , 2005, Glia.

[30]  D. Attwell,et al.  The role of glutamate transporters in glutamate homeostasis in the brain. , 1997, The Journal of experimental biology.

[31]  J. Pal,et al.  Clinical and model research of neurotrauma. , 2009, Methods in molecular biology.

[32]  L. Gardner,et al.  Leukocyte extravasation: chemokine transport and presentation by the endothelium. , 2002, Blood.

[33]  H. Luhmann,et al.  Volatile Anesthetics Influence Blood-Brain Barrier Integrity by Modulation of Tight Junction Protein Expression in Traumatic Brain Injury , 2012, PloS one.

[34]  B. Kelley,et al.  Neuroinflammatory Responses After Experimental Diffuse Traumatic Brain Injury , 2007, Journal of neuropathology and experimental neurology.

[35]  C. Cotman,et al.  Thrombin Induces Apoptosis in Cultured Neurons and Astrocytes via a Pathway Requiring Tyrosine Kinase and RhoA Activities , 1997, The Journal of Neuroscience.

[36]  Jialin C. Zheng,et al.  IL‐1β and TNF‐α induce neurotoxicity through glutamate production: a potential role for neuronal glutaminase , 2013, Journal of neurochemistry.

[37]  D. Darland,et al.  Endothelial cell-astrocyte interactions and TGF beta are required for induction of blood-neural barrier properties. , 2004, Brain research. Developmental brain research.

[38]  R. Keep,et al.  The role of thrombin and thrombin receptors in ischemic, hemorrhagic and traumatic brain injury: deleterious or protective? , 2002, Journal of neurochemistry.

[39]  Shiying Li,et al.  Tyrosine phosphorylation of VE-cadherin and claudin-5 is associated with TGF-β1-induced permeability of centrally derived vascular endothelium. , 2011, European journal of cell biology.

[40]  P. Deininger,et al.  Temporal changes in gene expression following cryogenic rat brain injury. , 1998, Brain research. Molecular brain research.

[41]  Mark Faul,et al.  Epidemiology of Traumatic Brain Injury , 2018, Textbook of Traumatic Brain Injury.

[42]  S. Kügler,et al.  Dendritic degeneration, neurovascular defects, and inflammation precede neuronal loss in a mouse model for tau-mediated neurodegeneration. , 2011, The American journal of pathology.

[43]  F. Dhabhar,et al.  Neurotoxic effects of polymorphonuclear granulocytes on hippocampal primary cultures , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[44]  P. Kochanek,et al.  One-year study of spatial memory performance, brain morphology, and cholinergic markers after moderate controlled cortical impact in rats. , 1999, Journal of neurotrauma.

[45]  W. Schaper,et al.  H2O2 induces paracellular permeability of porcine brain-derived microvascular endothelial cells by activation of the p44/42 MAP kinase pathway. , 2005, European journal of cell biology.

[46]  O. Alonso,et al.  Interleukin-1beta messenger ribonucleic acid and protein levels after fluid-percussion brain injury in rats: importance of injury severity and brain temperature. , 2002, Neurosurgery.

[47]  J. D. Richardson,et al.  Cellular Mechanisms of Neurogenic Inflammation , 2002, Journal of Pharmacology and Experimental Therapeutics.

[48]  J. Guralnik,et al.  Documented head injury in early adulthood and risk of Alzheimer’s disease and other dementias , 2000, Neurology.

[49]  O. Alonso,et al.  Early microvascular and neuronal consequences of traumatic brain injury: a light and electron microscopic study in rats. , 1994, Journal of neurotrauma.

[50]  Anti-Inflammatory Efficacy of Dexamethasone and Nrf2 Activators in the CNS Using Brain Slices as a Model of Acute Injury , 2012, Journal of Neuroimmune Pharmacology.

[51]  C. D. Sharp,et al.  Glutamate causes a loss in human cerebral endothelial barrier integrity through activation of NMDA receptor. , 2003, American journal of physiology. Heart and circulatory physiology.

[52]  R. Agarwal,et al.  Potential Role of Cerebral Glutathione in the Maintenance of Blood-Brain Barrier Integrity in Rat , 1999, Neurochemical Research.

[53]  D. Lawrence,et al.  Beta-transforming growth factor is stored in human blood platelets as a latent high molecular weight complex. , 1986, Biochemical and biophysical research communications.

[54]  E. Fleck,et al.  In vivo measurement of endothelium-dependent vasodilation with substance P in man. , 1992, Herz.

[55]  H. Wolburg,et al.  Brain endothelial cells and the glio-vascular complex , 2008, Cell and Tissue Research.

[56]  J. Ghersi-Egea,et al.  The Role of the Choroid Plexus in Neutrophil Invasion after Traumatic Brain Injury , 2009, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[57]  J. Badaut,et al.  Delayed increase of astrocytic aquaporin 4 after juvenile traumatic brain injury: Possible role in edema resolution? , 2012, Neuroscience.

[58]  A. Gearing,et al.  Immunohistochemistry of matrix metalloproteinases in reperfusion injury to rat brain: activation of MMP-9 linked to stromelysin-1 and microglia in cell cultures , 2001, Brain Research.

[59]  Bo Eun Lee,et al.  Prevention of traumatic brain injury-induced neuronal death by inhibition of NADPH oxidase activation , 2012, Brain Research.

[60]  A. Gulati,et al.  Use of magnesium in traumatic brain injury , 2011, Neurotherapeutics.

[61]  C. Hooper,et al.  Pure albumin is a potent trigger of calcium signalling and proliferation in microglia but not macrophages or astrocytes , 2005, Journal of neurochemistry.

[62]  F. Piehl,et al.  Strain influences on inflammatory pathway activation, cell infiltration and complement cascade after traumatic brain injury in the rat , 2013, Brain, Behavior, and Immunity.

[63]  L. Bi,et al.  Increased levels of calcitonin gene-related peptide in serum accelerate fracture healing following traumatic brain injury. , 2011, Molecular medicine reports.

[64]  A. Dray,et al.  Kinins and kinin receptors in the nervous system , 1995, Neurochemistry International.

[65]  M. Mullan,et al.  Repetitive mild traumatic brain injury augments tau pathology and glial activation in aged hTau mice. , 2013, Journal of neuropathology and experimental neurology.

[66]  A. Mankertz,et al.  Expression from the human occludin promoter is affected by tumor necrosis factor α and interferon γ , 2000 .

[67]  V. Perry,et al.  Loss of the tight junction proteins occludin and zonula occludens-1 from cerebral vascular endothelium during neutrophil-induced blood–brain barrier breakdown in vivo , 1998, Neuroscience.

[68]  M. Wainwright,et al.  Albumin activates astrocytes and microglia through mitogen-activated protein kinase pathways , 2010, Brain Research.

[69]  Jon Sinclair,et al.  Astroglia and glutamate in physiology and pathology: aspects on glutamate transport, glutamate-induced cell swelling and gap-junction communication , 2000, Neurochemistry International.

[70]  Stephen F Traynelis,et al.  Activation of Protease-Activated Receptor-1 Triggers Astrogliosis after Brain Injury , 2005, The Journal of Neuroscience.

[71]  F. Helmchen,et al.  Resting Microglial Cells Are Highly Dynamic Surveillants of Brain Parenchyma in Vivo , 2005, Science.

[72]  W. Armstead,et al.  Heat shock protein modulation of KATP and KCa channel cerebrovasodilation after brain injury. , 2005, American journal of physiology. Heart and circulatory physiology.

[73]  R. Vink,et al.  Mechanisms of cerebral edema in traumatic brain injury: therapeutic developments , 2010, Current opinion in neurology.

[74]  P. Fatouros,et al.  Regional cerebral blood volume after severe head injury in patients with regional cerebral ischemia. , 1998 .

[75]  G. Rosenberg,et al.  Gelatinase B modulates selective opening of the blood-brain barrier during inflammation. , 1998, American journal of physiology. Regulatory, integrative and comparative physiology.

[76]  I. Blasig,et al.  4-Hydroxynonenal impairs the permeability of an in vitro rat blood–brain barrier , 2001, Neuroscience Letters.

[77]  D. Lowenstein,et al.  Persistent memory dysfunction is associated with bilateral hippocampal damage following experimental brain injury , 1994, Neuroscience Letters.

[78]  R. Busto,et al.  Glutamate Release and Free Radical Production Following Brain Injury: Effects of Posttraumatic Hypothermia , 1995, Journal of neurochemistry.

[79]  Kirsten M. Lynch,et al.  Vasopressin amplifies the production of proinflammatory mediators in traumatic brain injury. , 2010, Journal of neurotrauma.

[80]  N. Plesnila,et al.  Temporal profile of thrombogenesis in the cerebral microcirculation after traumatic brain injury in mice. , 2010, Journal of neurotrauma.

[81]  N. Rothwell,et al.  Cytokines and the nervous system I: expression and recognition , 1995, Trends in Neurosciences.

[82]  A. Mankertz,et al.  Expression from the human occludin promoter is affected by tumor necrosis factor alpha and interferon gamma. , 2000, Journal of cell science.

[83]  S. Stein,et al.  Intravascular coagulation: a major secondary insult in nonfatal traumatic brain injury. , 2002, Journal of neurosurgery.

[84]  K. Ley,et al.  Opening the flood-gates: how neutrophil-endothelial interactions regulate permeability. , 2009, Trends in immunology.

[85]  Shijie Jin,et al.  Tumor Necrosis Factor-α Induces Neurotoxicity via Glutamate Release from Hemichannels of Activated Microglia in an Autocrine Manner* , 2006, Journal of Biological Chemistry.

[86]  J. Cheong,et al.  Metal transporters in intestine and brain: their involvement in metal-associated neurotoxicities , 2007, Human & experimental toxicology.

[87]  S. Heales,et al.  Differential effects of albumin on microglia and macrophages; implications for neurodegeneration following blood–brain barrier damage , 2009, Journal of neurochemistry.

[88]  D J Begley,et al.  Understanding and circumventing the blood‐brain barrier , 2003, Acta paediatrica (Oslo, Norway : 1992). Supplement.

[89]  M. Chopp,et al.  Neuroprotective and neurorestorative effects of thymosin β4 treatment initiated 6 hours after traumatic brain injury in rats. , 2012, Journal of neurosurgery.

[90]  Jeffrey F. Thompson,et al.  Matrix Metalloproteinase-Mediated Disruption of Tight Junction Proteins in Cerebral Vessels is Reversed by Synthetic Matrix Metalloproteinase Inhibitor in Focal Ischemia in Rat , 2007, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[91]  P. Kochanek,et al.  Early polymorphonuclear leukocyte accumulation correlates with the development of posttraumatic cerebral edema in rats. , 1990, Journal of neurotrauma.

[92]  M. Bullock,et al.  Aquaporin-1-mediated cerebral edema following traumatic brain injury: effects of acidosis and corticosteroid administration. , 2010, Journal of neurosurgery.

[93]  M. Montalto,et al.  Neutrophil-derived Glutamate Regulates Vascular Endothelial Barrier Function* , 2002, The Journal of Biological Chemistry.

[94]  E. Hall,et al.  "High-dose" methylprednisolone and CNS injury. , 1986, Journal of neurosurgery.

[95]  J. Szmydynger-Chodobska,et al.  Blood–Brain Barrier Pathophysiology in Traumatic Brain Injury , 2011, Translational Stroke Research.

[96]  R. Vink,et al.  A Substance P Antagonist Increases Brain Intracellular Free Magnesium Concentration after Diffuse Traumatic Brain Injury in Rats , 2004, Journal of the American College of Nutrition.

[97]  Margaret A. Parsley,et al.  Inflammatory consequences in a rodent model of mild traumatic brain injury. , 2013, Journal of neurotrauma.

[98]  H. C. Tsui,et al.  Expression of metabotropic glutamate receptors in rat meningeal and brain microvasculature and choroid plexus , 2003, The Journal of comparative neurology.

[99]  B. Lyeth,et al.  Astroglia: important mediators of traumatic brain injury. , 2007, Progress in brain research.

[100]  O. Hurtado,et al.  Inhibition of iNOS activity by 1400W decreases glutamate release and ameliorates stroke outcome after experimental ischemia , 2005, Neurobiology of Disease.

[101]  Donald W. Miller,et al.  Tumor Necrosis Factor-α Induces Cyclooxygenase-2 Expression and Prostaglandin Release in Brain Microvessel Endothelial Cells , 2001 .

[102]  K. Tateda,et al.  Expression of aquaporin-4 augments cytotoxic brain edema after traumatic brain injury during acute ethanol exposure. , 2012, The American journal of pathology.

[103]  J. Guralnik,et al.  Head injury in early adulthood and the lifetime risk of depression. , 2002, Archives of general psychiatry.

[104]  M. Nedergaard,et al.  The blood–brain barrier: an overview Structure, regulation, and clinical implications , 2004, Neurobiology of Disease.

[105]  R. Bonavia,et al.  Characterization of chemokines and their receptors in the central nervous system: physiopathological implications , 2002, Journal of neurochemistry.

[106]  J J Crisco,et al.  Solitary sclerosis: Progressive myelopathy from solitary demyelinating lesion , 2012, Neurology.