Reactive Astrocytes in Neural Repair and Protection

Reactive astrocytosis occurs prominently in response to all forms of CNS injury or disease. The functions of reactive astrocytes are not well understood, and both harmful and beneficial activities have been attributed to these cells. The basic process of reactive astrocytosis is conserved in vertebrate evolution, suggesting fitness-enhancing benefits, but scar-forming reactive astrocytes are often regarded as uniformly detrimental to clinical outcome, in particular, when implicated as inhibitors of axon regeneration. Transgenic mouse models are providing new means to study the activities of reactive astrocytes after CNS insults in vivo. Recent studies point toward roles for reactive astrocytes in restricting inflammation and protecting neurons and oligodendrocytes, thereby helping to limit tissue degeneration and preserve function after CNS injury.

[1]  M. Hediger,et al.  Knockout of Glutamate Transporters Reveals a Major Role for Astroglial Transport in Excitotoxicity and Clearance of Glutamate , 1996, Neuron.

[2]  B. Barres,et al.  Control of synapse number by glia. , 2001, Science.

[3]  D. Butterfield,et al.  Human endogenous retrovirus glycoprotein–mediated induction of redox reactants causes oligodendrocyte death and demyelination , 2004, Nature Neuroscience.

[4]  B. MacVicar,et al.  Calcium transients in astrocyte endfeet cause cerebrovascular constrictions , 2004, Nature.

[5]  B. Sauer Site-specific recombination: developments and applications. , 1994, Current opinion in biotechnology.

[6]  F. Gage,et al.  Astrocytes are important for sprouting in the septohippocampal circuit , 1988, Experimental Neurology.

[7]  M. Sofroniew,et al.  GFAP-expressing progenitors are the principal source of constitutive neurogenesis in adult mouse forebrain , 2004, Nature Neuroscience.

[8]  M. Hatten,et al.  Astroglia in CNS injury , 1991, Glia.

[9]  Mary P Galea,et al.  Axonal Regeneration and Lack of Astrocytic Gliosis in EphA4-Deficient Mice , 2004, The Journal of Neuroscience.

[10]  Jerry Silver,et al.  Regeneration beyond the glial scar , 2004, Nature Reviews Neuroscience.

[11]  Clive N Svendsen,et al.  Leukocyte Infiltration, Neuronal Degeneration, and Neurite Outgrowth after Ablation of Scar-Forming, Reactive Astrocytes in Adult Transgenic Mice , 1999, Neuron.

[12]  Mark Ellisman,et al.  Absence of Glial Fibrillary Acidic Protein and Vimentin Prevents Hypertrophy of Astrocytic Processes and Improves Post-Traumatic Regeneration , 2004, The Journal of Neuroscience.

[13]  Jerry Silver,et al.  Astrocyte-Associated Fibronectin Is Critical for Axonal Regeneration in Adult White Matter , 2004, The Journal of Neuroscience.

[14]  A. Privat,et al.  Axonal plasticity and functional recovery after spinal cord injury in mice deficient in both glial fibrillary acidic protein and vimentin genes , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[15]  J. O'Callaghan,et al.  Induction of gp130-related Cytokines and Activation of JAK2/STAT3 Pathway in Astrocytes Precedes Up-regulation of Glial Fibrillary Acidic Protein in the 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine Model of Neurodegeneration , 2004, Journal of Biological Chemistry.

[16]  P. Haydon,et al.  Book Review: Glutamate on Demand: Astrocytes as a Ready Source , 2001, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[17]  L. Mucke,et al.  Indicator expression directed by regulatory sequences of the glial fibrillary acidic protein (GFAP) gene: In vivo comparison of distinct GFAP‐lacZ transgenes , 1995, Glia.

[18]  H. Kikutani,et al.  Roles of the semaphorin family in immune regulation. , 2003, Advances in immunology.

[19]  R. Hershkoviz,et al.  Interactions of migrating T lymphocytes, inflammatory mediators, and the extracellular matrix. , 1995, Critical reviews in immunology.

[20]  B. Liu,et al.  Glaucomatous Optic Neuropathy: When Glia Misbehave , 2003, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[21]  C. Brosnan,et al.  Cytokines: Powerful Regulators of Glial Cell Activation , 2003, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[22]  R. Gadagkar Nothing in Biology Makes Sense Except in the Light of Evolution , 2005 .

[23]  Daniel A. Lim,et al.  Subventricular Zone Astrocytes Are Neural Stem Cells in the Adult Mammalian Brain , 1999, Cell.

[24]  R. Berman,et al.  Early loss of astrocytes after experimental traumatic brain injury , 2003, Glia.

[25]  Kazuyuki Murase,et al.  Glial Nitric Oxide-Mediated Long-Term Presynaptic Facilitation Revealed by Optical Imaging in Rat Spinal Dorsal Horn , 2004, The Journal of Neuroscience.

[26]  J. Ellison,et al.  Astrocytic demise precedes delayed neuronal death in focal ischemic rat brain. , 1999, Brain research. Molecular brain research.

[27]  L. Mucke,et al.  Fulminant Jejuno-Ileitis following Ablation of Enteric Glia in Adult Transgenic Mice , 1998, Cell.

[28]  Pierre J Magistretti,et al.  Neuroenergetics: Calling Upon Astrocytes to Satisfy Hungry Neurons , 2004, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[29]  W. Webb,et al.  Neural Activity Triggers Neuronal Oxidative Metabolism Followed by Astrocytic Glycolysis , 2004, Science.

[30]  Ngan B. Doan,et al.  Reactive Astrocytes Protect Tissue and Preserve Function after Spinal Cord Injury , 2004, The Journal of Neuroscience.

[31]  Fred H. Gage,et al.  Reactive astrocytes are substrates for the growth of adult CNS axons in the presence of elevated levels of nerve growth factor , 1991, Neuron.

[32]  I. Klatzo,et al.  Presidental address. Neuropathological aspects of brain edema. , 1967, Journal of neuropathology and experimental neurology.