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Reactive Astrocytes, Astrocyte Intermediate Filament Proteins, and Their Role in the Disease Pathogenesis

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Part of the book series: Neuromethods ((NM,volume 79))

Abstract

Astrocyte activation and reactive gliosis are seen in many neuropathologies, e.g., neurotrauma, stroke, epilepsy, or neurodegenerative diseases. Astrocyte activation alters gene expression and leads to morphological and functional changes in astrocytes with important functional consequences for the central nervous system (Eddleston and Mucke, Neuroscience 54:15-36, 1993; Eng and Ghirnikar, Brain Pathol 4:229-237, 1994; Hernandez et al., Glia 38:45-64, 2002; Pekny and Nilsson, Glia 50:427-434, 2005; Wilhelmsson et al., Proc Natl Acad Sci U S A 103:17513-17518, 2006; Sofroniew, Trends Neurosci 32:638-647, 2009; Sofroniew and Vinters, Acta Neuropathol 119:7-35, 2010). The understanding of astrocyte activation and reactive gliosis in pathological situations remains incomplete but the increasing amount of experimental evidence points to its importance in disease pathogenesis (Wilhelmsson et al., J Neurosci 24:5016-5021, 2004; Sofroniew, Neuroscientist 11:400-407, 2005; Maragakis and Rothstein, Nat Clin Pract Neurol 2:679-689, 2006; Seifert et al., Nat Rev Neurosci 7:194-206, 2006; Correa-Cerro and Mandell, J Neuropathol Exp Neurol 66:169-76, 2007; Barres, Neuron 60:430-440, 2008; Li et al., J Cereb Blood Flow Metab 28:468-481, 2008; Macauley et al. J Neurosci 31:15575-15585, 2011). One of the principal hallmarks of astrocyte activation and reactive gliosis is the upregulation of astrocyte intermediate filament (nanofilament) proteins and reorganization of intermediate filaments that are part of the cytoskeleton. This review focuses on the role of the intermediate filament system of astrocytes in neuropathological context and presents some of the relevant model systems.

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References

  1. Eddleston M, Mucke L (1993) Molecular profile of reactive astrocytes–implications for their role in neurologic disease. Neuroscience 54:15–36

    Article  PubMed  CAS  Google Scholar 

  2. Eng LF, Ghirnikar RS (1994) GFAP and astrogliosis. Brain Pathol 4:229–237

    Article  PubMed  CAS  Google Scholar 

  3. Hernandez MR, Agapova OA, Yang P et al (2002) Differential gene expression in astrocytes from human normal and glaucomatous optic nerve head analyzed by cDNA microarray. Glia 38:45–64

    Article  PubMed  Google Scholar 

  4. Pekny M, Nilsson M (2005) Astrocyte activation and reactive gliosis. Glia 50:427–434

    Article  PubMed  Google Scholar 

  5. Wilhelmsson U, Bushong EA, Price DL et al (2006) Redefining the concept of reactive astrocytes as cells that remain within their unique domains upon reaction to injury. Proc Natl Acad Sci U S A 103:17513–17518

    Article  PubMed  CAS  Google Scholar 

  6. Sofroniew MV (2009) Molecular dissection of reactive astrogliosis and glial scar formation. Trends Neurosci 32:638–647

    Article  PubMed  CAS  Google Scholar 

  7. Sofroniew MV, Vinters HV (2010) Astrocytes: biology and pathology. Acta Neuropathol 119:7–35

    Article  PubMed  Google Scholar 

  8. Wilhelmsson U, Li L, Pekna M et al (2004) Absence of glial fibrillary acidic protein and vimentin prevents hypertrophy of astrocytic processes and improves post-traumatic regeneration. J Neurosci 24:5016–5021

    Article  PubMed  CAS  Google Scholar 

  9. Sofroniew MV (2005) Reactive astrocytes in neural repair and protection. Neuroscientist 11:400–407

    Article  PubMed  CAS  Google Scholar 

  10. Maragakis NJ, Rothstein JD (2006) Mechanisms of disease: astrocytes in neurodegenerative disease. Nat Clin Pract Neurol 2:679–689

    Article  PubMed  CAS  Google Scholar 

  11. Seifert G, Schilling K, Steinhauser C (2006) Astrocyte dysfunction in neurological disorders: a molecular perspective. Nat Rev Neurosci 7:194–206

    Article  PubMed  CAS  Google Scholar 

  12. Correa-Cerro LS, Mandell JW (2007) Molecular mechanisms of astrogliosis: new approaches with mouse genetics. J Neuropathol Exp Neurol 66:169–176

    Article  PubMed  CAS  Google Scholar 

  13. Barres BA (2008) The mystery and magic of glia: a perspective on their roles in health and disease. Neuron 60:430–440

    Article  PubMed  CAS  Google Scholar 

  14. Li L, Lundkvist A, Andersson D et al (2008) Protective role of reactive astrocytes in brain ischemia. J Cereb Blood Flow Metab 28:468–481

    Article  PubMed  CAS  Google Scholar 

  15. Macauley SL, Pekny M, Sands MS (2011) The role of attenuated astrocyte activation in infantile neuronal ceroid lipofuscinosis. J Neurosci 31:15575–15585

    Article  PubMed  CAS  Google Scholar 

  16. Kosaka T, Hama K (1986) Three-dimensional structure of astrocytes in the rat dentate gyrus. J Comp Neurol 249:242–260

    Article  PubMed  CAS  Google Scholar 

  17. Grosche J, Matyash V, Moller T et al (1999) Microdomains for neuron-glia interaction: parallel fiber signaling to Bergmann glial cells. Nat Neurosci 2:139–143

    Article  PubMed  CAS  Google Scholar 

  18. Bushong EA, Martone ME, Jones YZ et al (2002) Protoplasmic astrocytes in CA1 stratum radiatum occupy separate anatomical domains. J Neurosci 22:183–192

    PubMed  CAS  Google Scholar 

  19. Bushong EA, Martone ME, Ellisman MH (2004) Maturation of astrocyte morphology and the establishment of astrocyte domains during postnatal hippocampal development. Int J Dev Neurosci 22:73–86

    Article  PubMed  Google Scholar 

  20. Haber M, Murai KK (2006) Reshaping neuron-glial communication at hippocampal synapses. Neuron Glia Biol 2:59–66

    Article  PubMed  Google Scholar 

  21. Simard M, Nedergaard M (2004) The neurobiology of glia in the context of water and ion homeostasis. Neuroscience 129:877–896

    Article  PubMed  CAS  Google Scholar 

  22. Pellerin L, Bouzier-Sore AK, Aubert A et al (2007) Activity-dependent regulation of energy metabolism by astrocytes: an update. Glia 55:1251–1262

    Article  PubMed  Google Scholar 

  23. Rouach N, Koulakoff A, Abudara V et al (2008) Astroglial metabolic networks sustain hippocampal synaptic transmission. Science 322:1551–1555

    Article  PubMed  CAS  Google Scholar 

  24. Suzuki A, Stern SA, Bozdagi O et al (2011) Astrocyte-neuron lactate transport is required for long-term memory formation. Cell 144:810–823

    Article  PubMed  CAS  Google Scholar 

  25. Ullian EM, Sapperstein SK, Christopherson KS et al (2001) Control of synapse number by glia. Science 291:657–661

    Article  PubMed  CAS  Google Scholar 

  26. Ullian EM, Christopherson KS, Barres BA (2004) Role for glia in synaptogenesis. Glia 47:209–216

    Article  PubMed  Google Scholar 

  27. Christopherson KS, Ullian EM, Stokes CC et al (2005) Thrombospondins are astrocyte-secreted proteins that promote CNS synaptogenesis. Cell 120:421–433

    Article  PubMed  CAS  Google Scholar 

  28. Eroglu C, Barres BA (2010) Regulation of synaptic connectivity by glia. Nature 468:223–231

    Article  PubMed  CAS  Google Scholar 

  29. Liebner S, Czupalla CJ, Wolburg H (2011) Current concepts of blood–brain barrier development. Int J Dev Biol 55:467–476

    Google Scholar 

  30. Zonta M, Angulo MC, Gobbo S et al (2003) Neuron-to-astrocyte signaling is central to the dynamic control of brain microcirculation. Nat Neurosci 6:43–50

    Article  PubMed  CAS  Google Scholar 

  31. Mulligan SJ, MacVicar BA (2004) Calcium transients in astrocyte endfeet cause cerebrovascular constrictions. Nature 431:195–199

    Article  PubMed  CAS  Google Scholar 

  32. Oberheim NA, Takano T, Han X et al (2009) Uniquely hominid features of adult human astrocytes. J Neurosci 29:3276–3287

    Article  PubMed  CAS  Google Scholar 

  33. Matyash V, Kettenmann H (2010) Heterogeneity in astrocyte morphology and physiology. Brain Res Rev 63:2–10

    Article  PubMed  CAS  Google Scholar 

  34. Zhang Y, Barres BA (2010) Astrocyte heterogeneity: an underappreciated topic in neurobiology. Curr Opin Neurobiol 20:588–594

    Article  PubMed  CAS  Google Scholar 

  35. Beckervordersandforth R, Tripathi P, Ninkovic J et al (2010) In vivo fate mapping and expression analysis reveals molecular hallmarks of prospectively isolated adult neural stem cells. Cell Stem Cell 7:744–758

    Article  PubMed  CAS  Google Scholar 

  36. Ståhlberg A, Andersson D, Aurelius J et al. (2011) Defining cell populations with single-cell gene expression profiling: correlations and identification of astrocyte subpopulations. Nucleic Acids Res 39:e24

    Google Scholar 

  37. Eng LF, Ghirnikar RS, Lee YL (2000) Glial fibrillary acidic protein: GFAP-thirty-one years (1969–2000). Neurochem Res 25:1439–1451

    Article  PubMed  CAS  Google Scholar 

  38. Okada S, Nakamura M, Katoh H et al (2006) Conditional ablation of Stat3 or Socs3 discloses a dual role for reactive astrocytes after spinal cord injury. Nat Med 12:829–834

    Article  PubMed  CAS  Google Scholar 

  39. Herrmann JE, Imura T, Song B et al (2008) STAT3 is a critical regulator of astrogliosis and scar formation after spinal cord injury. J Neurosci 28:7231–7243

    Article  PubMed  CAS  Google Scholar 

  40. Renault-Mihara F, Okada S, Shibata S et al (2008) Spinal cord injury: emerging beneficial role of reactive astrocytes’ migration. Int J Biochem Cell Biol 40:1649–1653

    Article  PubMed  CAS  Google Scholar 

  41. Voskuhl RR, Peterson RS, Song B et al (2009) Reactive astrocytes form scar-like perivascular barriers to leukocytes during adaptive immune inflammation of the CNS. J Neurosci 29:11511–11522

    Article  PubMed  CAS  Google Scholar 

  42. Silver J, Miller JH (2004) Regeneration beyond the glial scar. Nat Rev Neurosci 5:146–156

    Article  PubMed  CAS  Google Scholar 

  43. Delaney CL, Brenner M, Messing A (1996) Conditional ablation of cerebellar astrocytes in postnatal transgenic mice. J Neurosci 16:6908–6918

    PubMed  CAS  Google Scholar 

  44. Bush TG, Puvanachandra N, Horner CH et al (1999) Leukocyte infiltration, neuronal degeneration, and neurite outgrowth after ablation of scar-forming, reactive astrocytes in adult transgenic mice. Neuron 23:297–308

    Article  PubMed  CAS  Google Scholar 

  45. Sofroniew MV, Bush TG, Blumauer N et al (1999) Genetically-targeted and conditionally-regulated ablation of astroglial cells in the central, enteric and peripheral nervous systems in adult transgenic mice. Brain Res 835:91–95

    Article  PubMed  CAS  Google Scholar 

  46. Faulkner JR, Herrmann JE, Woo MJ et al (2004) Reactive astrocytes protect tissue and preserve function after spinal cord injury. J Neurosci 24:2143–2155

    Article  PubMed  CAS  Google Scholar 

  47. Garcia AD, Doan NB, Imura T et al (2004) GFAP-expressing progenitors are the principal source of constitutive neurogenesis in adult mouse forebrain. Nat Neurosci 7:1233–1241

    Article  PubMed  CAS  Google Scholar 

  48. Eliasson C, Sahlgren C, Berthold CH et al (1999) Intermediate filament protein partnership in astrocytes. J Biol Chem 274:23996–24006

    Article  PubMed  CAS  Google Scholar 

  49. Pekny M, Johansson CB, Eliasson C et al (1999) Abnormal reaction to central nervous system injury in mice lacking glial fibrillary acidic protein and vimentin. J Cell Biol 145:503–514

    Article  PubMed  CAS  Google Scholar 

  50. Lu YB, Iandiev I, Hollborn M et al (2011) Reactive glial cells: increased stiffness correlates with increased intermediate filament expression. FASEB J 25:624–631

    Article  PubMed  CAS  Google Scholar 

  51. Lepekhin EA, Eliasson C, Berthold CH et al (2001) Intermediate filaments regulate astrocyte motility. J Neurochem 79:617–625

    Article  PubMed  CAS  Google Scholar 

  52. Potokar M, Kreft M, Li L et al (2007) Cytoskeleton and vesicle mobility in astrocytes. Traffic 8:12–20

    Article  PubMed  CAS  Google Scholar 

  53. Potokar M, Stenovec M, Gabrijel M et al (2010) Intermediate filaments attenuate stimulation-dependent mobility of endosomes/lysosomes in astrocytes. Glia 58:1208–1219

    PubMed  Google Scholar 

  54. Ding M, Eliasson C, Betsholtz C et al (1998) Altered taurine release following hypotonic stress in astrocytes from mice deficient for GFAP and vimentin. Brain Res Mol Brain Res 62:77–81

    Article  PubMed  CAS  Google Scholar 

  55. Cho KS, Yang L, Lu B et al (2005) Re-establishing the regenerative potential of central nervous system axons in postnatal mice. J Cell Sci 118:863–872

    Article  PubMed  CAS  Google Scholar 

  56. Menet V, Prieto M, Privat A et al (2003) Axonal plasticity and functional recovery after spinal cord injury in mice deficient in both glial fibrillary acidic protein and vimentin genes. Proc Natl Acad Sci U S A 100:8999–9004

    Article  PubMed  CAS  Google Scholar 

  57. Kinouchi R, Takeda M, Yang L et al (2003) Robust neural integration from retinal transplants in mice deficient in GFAP and vimentin. Nat Neurosci 6:863–868

    Article  PubMed  CAS  Google Scholar 

  58. Widestrand A, Faijerson J, Wilhelmsson U et al (2007) Increased neurogenesis and astrogenesis from neural progenitor cells grafted in the hippocampus of GFAP−/− Vim−/− mice. Stem Cells 25:2619–2627

    Article  PubMed  CAS  Google Scholar 

  59. Davies SJ, Goucher DR, Doller C et al (1999) Robust regeneration of adult sensory axons in degenerating white matter of the adult rat spinal cord. J Neurosci 19:5810–5822

    PubMed  CAS  Google Scholar 

  60. Goldshmit Y, Galea MP, Wise G et al (2004) Axonal regeneration and lack of astrocytic gliosis in EphA4-deficient mice. J Neurosci 24:10064–10073

    Article  PubMed  CAS  Google Scholar 

  61. Busch SA, Silver J (2007) The role of extracellular matrix in CNS regeneration. Curr Opin Neurobiol 17:120–127

    Article  PubMed  CAS  Google Scholar 

  62. Fitch MT, Silver J (2008) CNS injury, glial scars, and inflammation: inhibitory extracellular matrices and regeneration failure. Exp Neurol 209:294–301

    Article  PubMed  CAS  Google Scholar 

  63. Alilain WJ, Horn KP, Hu H et al (2011) Functional regeneration of respiratory pathways after spinal cord injury. Nature 475:196–200

    Article  PubMed  CAS  Google Scholar 

  64. Myer DJ, Gurkoff GG, Lee SM et al (2006) Essential protective roles of reactive astrocytes in traumatic brain injury. Brain 129:2761–2772

    Article  PubMed  CAS  Google Scholar 

  65. Kimelberg HK, Nedergaard M (2010) Functions of astrocytes and their potential as therapeutic targets. Neurotherapeutics 7:338–353

    Article  PubMed  CAS  Google Scholar 

  66. Parpura V, Heneka MT, Montana V et al (2012) Glial cells in (patho)physiology. J Neurochem 121:4–27

    Article  PubMed  CAS  Google Scholar 

  67. Pekna M, Pekny M, Nilsson M (2012) Modulation of neural plasticity as a basis for stroke rehabilitation. Stroke, in press.

    Google Scholar 

  68. Lovatt D, Sonnewald U, Waagepetersen HS et al (2007) The transcriptome and metabolic gene signature of protoplasmic astrocytes in the adult murine cortex. J Neurosci 27:12255–12266

    Article  PubMed  CAS  Google Scholar 

  69. Cahoy JD, Emery B, Kaushal A et al (2008) A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function. J Neurosci 28:264–278

    Article  PubMed  CAS  Google Scholar 

  70. Lipton SA, Gu Z, Nakamura T (2007) Inflammatory mediators leading to protein misfolding and uncompetitive/fast off-rate drug therapy for neurodegenerative disorders. Int Rev Neurobiol 82:1–27

    Article  PubMed  CAS  Google Scholar 

  71. Nilsson M, Pekny M (2007) Enriched environment and astrocytes in central nervous system regeneration. J Rehabil Med 39:345–352

    Article  PubMed  Google Scholar 

  72. Deller T, Frotscher M (1997) Lesion-induced plasticity of central neurons: sprouting of single fibres in the rat hippocampus after unilateral entorhinal cortex lesion. Prog Neurobiol 53:687–727

    Article  PubMed  CAS  Google Scholar 

  73. Turner DA, Buhl EH, Hailer NP et al (1998) Morphological features of the entorhinal-hippocampal connection. Prog Neurobiol 55:537–562

    Article  PubMed  CAS  Google Scholar 

  74. Deller T, Del Turco D, Rappert A et al (2007) Structural reorganization of the dentate gyrus following entorhinal denervation: species differences between rat and mouse. Prog Brain Res 163:501–528

    Article  PubMed  CAS  Google Scholar 

  75. Steward O, Kelley MS, Torre ER (1993) The process of reinnervation in the dentate gyrus of adult rats: temporal relationship between changes in the levels of glial fibrillary acidic protein (GFAP) and GFAP mRNA in reactive astrocytes. Exp Neurol 124:167–183

    Article  PubMed  CAS  Google Scholar 

  76. Steward O, Torre ER, Phillips LL et al (1990) The process of reinnervation in the dentate gyrus of adult rats: time course of increases in mRNA for glial fibrillary acidic protein. J Neurosci 10:2373–2384

    PubMed  CAS  Google Scholar 

  77. Rose G, Lynch G, Cotman CW (1976) Hypertrophy and redistribution of astrocytes in the deafferented dentate gyrus. Brain Res Bull 1:87–92

    Article  PubMed  CAS  Google Scholar 

  78. Krohn K, Laping NJ, Morgan TE et al (1995) Expression of vimentin increases in the hippocampus and cerebral cortex after entorhinal cortex lesioning and in response to transforming growth factor beta 1. J Neuroimmunol 56:53–63

    Article  PubMed  CAS  Google Scholar 

  79. Jing R, Wilhelmsson U, Goodwill W et al (2007) Synemin is expressed in reactive astrocytes in neurotrauma and interacts differentially with vimentin and GFAP intermediate filament networks. J Cell Sci 120:1267–1277

    Article  PubMed  CAS  Google Scholar 

  80. Jensen MB, Finsen B, Zimmer J (1997) Morphological and immunophenotypic microglial changes in the denervated fascia dentata of adult rats: correlation with blood–brain barrier damage and astroglial reactions. Exp Neurol 143:103–116

    Article  PubMed  CAS  Google Scholar 

  81. Dehn D, Burbach GJ, Schafer R et al (2006) NG2 upregulation in the denervated rat fascia dentata following unilateral entorhinal cortex lesion. Glia 53:491–500

    Article  PubMed  Google Scholar 

  82. Deller T, Haas CA, Frotscher M (2000) Reorganization of the rat fascia dentata after a unilateral entorhinal cortex lesion. Role of the extracellular matrix. Ann NY Acad Sci 911:207–220

    Article  PubMed  CAS  Google Scholar 

  83. Owens T, Babcock AA, Millward JM et al (2005) Cytokine and chemokine inter-regulation in the inflamed or injured CNS. Brain Res Brain Res Rev 48:178–184

    Article  PubMed  CAS  Google Scholar 

  84. Bechmann I, Nitsch R (1997) Astrocytes and microglial cells incorporate degenerating fibers following entorhinal lesion: a light, confocal, and electron microscopical study using a phagocytosis-dependent labeling technique. Glia 20:145–154

    Article  PubMed  CAS  Google Scholar 

  85. Vuksic M, Del Turco D, Vlachos A et al (2011) Unilateral entorhinal denervation leads to long-lasting dendritic alterations of mouse hippocampal granule cells. Exp Neurol 230:176–185, Epub 2011 Apr 22

    Article  PubMed  Google Scholar 

  86. Steward O, Cotman CW, Lynch GS (1974) Growth of a new fiber projection in the brain of adult rats: re-innervation of the dentate gyrus by the contralateral entorhinal cortex following ipsilateral entorhinal lesions. Exp Brain Res 20:45–66

    Article  PubMed  CAS  Google Scholar 

  87. Guthrie KM, Nguyen T, Gall CM (1995) Insulin-like growth factor-1 mRNA is increased in deafferented hippocampus: spatiotemporal correspondence of a trophic event with axon sprouting. J Comp Neurol 352:147–160

    Article  PubMed  CAS  Google Scholar 

  88. Eijkenboom M, Blokland A, van der Staay FJ (2000) Modelling cognitive dysfunctions with bilateral injections of ibotenic acid into the rat entorhinal cortex. Neuroscience 101:27–39

    Article  PubMed  CAS  Google Scholar 

  89. Kadish I, Van Groen T (2003) Differences in lesion-induced hippocampal plasticity between mice and rats. Neuroscience 116:499–509

    Article  PubMed  CAS  Google Scholar 

  90. Kelley MS, Steward O (1996) The process of reinnervation in the dentate gyrus of adult rats: physiological events at the time of the lesion and during the early postlesion period. Exp Neurol 139:73–82

    Article  PubMed  CAS  Google Scholar 

  91. Gwag BJ, Sessler F, Kimmerer K et al (1994) Neurotrophic factor mRNA expression in dentate gyrus is increased following angular bundle transection. Brain Res 647:23–29

    Article  PubMed  CAS  Google Scholar 

  92. Deller T, Frotscher M, Nitsch R (1995) Morphological evidence for the sprouting of inhibitory commissural fibers in response to the lesion of the excitatory entorhinal input to the rat dentate gyrus. J Neurosci 15:6868–6878

    PubMed  CAS  Google Scholar 

  93. Jensen MB, Hegelund IV, Poulsen FR et al (1999) Microglial reactivity correlates to the density and the myelination of the anterogradely degenerating axons and terminals following perforant path denervation of the mouse fascia dentata. Neuroscience 93:507–518

    Article  PubMed  CAS  Google Scholar 

  94. Del Turco D, Woods AG, Gebhardt C et al (2003) Comparison of commissural sprouting in the mouse and rat fascia dentata after entorhinal cortex lesion. Hippocampus 13:685–699

    Article  PubMed  Google Scholar 

  95. Sihlbom C, Wilhelmsson U, Li L et al (2007) 14-3-3 Expression in denervated hippocampus after entorhinal cortex lesion assessed by culture-derived isotope tags in quantitative proteomics. J Proteome Res 6:3491–3500

    Article  PubMed  CAS  Google Scholar 

  96. Rosenblum WI, El-Sabban F (1977) Effects of combined parenchymal and vascular injury on platelet aggregation in pial arterioles of living mice: evidence for release of aggregate-inhibiting materials. Stroke 8:691–693

    Article  PubMed  CAS  Google Scholar 

  97. Watson BD, Dietrich WD, Busto R et al (1985) Induction of reproducible brain infarction by photochemically initiated thrombosis. Ann Neurol 17:497–504

    Article  PubMed  CAS  Google Scholar 

  98. Dietrich WD, Watson BD, Busto R et al (1987) Photochemically induced cerebral infarction. I. Early microvascular alterations. Acta Neuropathol 72:315–325

    Article  PubMed  CAS  Google Scholar 

  99. Boquillon M, Boquillon JP, Bralet J (1992) Photochemically induced, graded cerebral infarction in the mouse by laser irradiation evolution of brain edema. J Pharmacol Toxicol Methods 27:1–6

    Article  PubMed  CAS  Google Scholar 

  100. Grome JJ, Gojowczyk G, Hofmann W et al (1988) Quantitation of photochemically induced focal cerebral ischemia in the rat. J Cereb Blood Flow Metab 8:89–95

    Article  PubMed  CAS  Google Scholar 

  101. Demougeot C, Bertrand N, Prigent-Tessier A et al (2003) Reversible loss of N-acetyl-aspartate in rats subjected to long-term focal cerebral ischemia. J Cereb Blood Flow Metab 23:482–489

    Article  PubMed  CAS  Google Scholar 

  102. Fujioka M, Taoka T, Matsuo Y et al (1999) Novel brain ischemic change on MRI. Delayed ischemic hyperintensity on T1-weighted images and selective neuronal death in the caudoputamen of rats after brief focal ischemia. Stroke 30:1043–1046

    Article  PubMed  CAS  Google Scholar 

  103. Yao H, Sugimori H, Fukuda K et al (2003) Photothrombotic middle cerebral artery occlusion and reperfusion laser system in spontaneously hypertensive rats. Stroke 34:2716–2721

    Article  PubMed  Google Scholar 

  104. Petito CK, Morgello S, Felix JC et al (1990) The two patterns of reactive astrocytosis in postischemic rat brain. J Cereb Blood Flow Metab 10:850–859

    Article  PubMed  CAS  Google Scholar 

  105. Brenner M (1994) Structure and transcriptional regulation of the GFAP gene. Brain Pathol 4:245–257

    Article  PubMed  CAS  Google Scholar 

  106. Schroeter M, Schiene K, Kraemer M et al (1995) Astroglial responses in photochemically induced focal ischemia of the rat cortex. Exp Brain Res 106:1–6

    Article  PubMed  CAS  Google Scholar 

  107. Schroeter M, Franke C, Stoll G et al (2001) Dynamic changes of magnetic resonance imaging abnormalities in relation to inflammation and glial responses after photothrombotic cerebral infarction in the rat brain. Acta Neuropathol 101:114–122

    PubMed  CAS  Google Scholar 

  108. Nowicka D, Rogozinska K, Aleksy M et al (2008) Spatiotemporal dynamics of astroglial and microglial responses after photothrombotic stroke in the rat brain. Acta Neurobiol Exp 68:155–168

    Google Scholar 

  109. Snape MF, Baldwin HA, Cross AJ et al (1993) The effects of chlormethiazole and nimodipine on cortical infarct area after focal cerebral ischaemia in the rat. Neuroscience 53:837–844

    Article  PubMed  CAS  Google Scholar 

  110. Bailey SJ, Wood NI, Samson NA et al (1995) Failure of isradipine to reduce infarct size in mouse, gerbil, and rat models of cerebral ischemia. Stroke 26:2177–2183

    Article  PubMed  CAS  Google Scholar 

  111. De Ryck M, Keersmaekers R, Duytschaever H et al (1996) Lubeluzole protects sensorimotor function and reduces infarct size in a photochemical stroke model in rats. J Pharmacol Exp Ther 279:748–758

    PubMed  Google Scholar 

  112. Chang YY, Fujimura M, Morita-Fujimura Y et al (1999) Neuroprotective effects of an antioxidant in cortical cerebral ischemia: prevention of early reduction of the apurinic/apyrimidinic endonuclease DNA repair enzyme. Neurosci Lett 277:61–64

    Article  PubMed  CAS  Google Scholar 

  113. Kharlamov A, Guidotti A, Costa E et al (1993) Semisynthetic sphingolipids prevent protein kinase C translocation and neuronal damage in the perifocal area following a photochemically induced thrombotic brain cortical lesion. J Neurosci 13:2483–2494

    PubMed  CAS  Google Scholar 

  114. Wood NI, Sopesen BV, Roberts JC et al (1996) Motor dysfunction in a photothrombotic focal ischaemia model. Behav Brain Res 78:113–120

    Article  PubMed  CAS  Google Scholar 

  115. Shanina EV, Schallert T, Witte OW et al (2006) Behavioral recovery from unilateral photothrombotic infarcts of the forelimb sensorimotor cortex in rats: role of the contralateral cortex. Neuroscience 139:1495–1506

    Article  PubMed  CAS  Google Scholar 

  116. Sugimori H, Yao H, Ooboshi H et al (2004) Krypton laser-induced photothrombotic distal middle cerebral artery occlusion without craniectomy in mice. Brain Res Brain Res Protoc 13:189–196

    Article  PubMed  Google Scholar 

  117. Hu X, Wester P, Brannstrom T et al (2001) Progressive and reproducible focal cortical ischemia with or without late spontaneous reperfusion generated by a ring-shaped, laser-driven photothrombotic lesion in rats. Brain Res Brain Res Protoc 7:76–85

    Article  PubMed  CAS  Google Scholar 

  118. Schroeter M, Jander S, Huitinga I et al (1997) Phagocytic response in photochemically induced infarction of rat cerebral cortex. The role of resident microglia. Stroke 28:382–386

    Article  PubMed  CAS  Google Scholar 

  119. Schroeter M, Jander S, Witte OW et al (1994) Local immune responses in the rat cerebral cortex after middle cerebral artery occlusion. J Neuroimmunol 55:195–203

    Article  PubMed  CAS  Google Scholar 

  120. Jander S, Kraemer M, Schroeter M et al (1995) Lymphocytic infiltration and expression of intercellular adhesion molecule-1 in photochemically induced ischemia of the rat cortex. J Cereb Blood Flow Metab 15:42–51

    Article  PubMed  CAS  Google Scholar 

  121. Madinier A, Bertrand N, Mossiat C et al (2008) Microglial involvement in neuroplastic changes following focal brain ischemia in rats. PLoS One 4:e8101

    Article  CAS  Google Scholar 

  122. Buchkremer-Ratzmann I, Witte OW (1997) Pharmacological reduction of electrophysiological diaschisis after photothrombotic ischemia in rat neocortex. Eur J Pharmacol 320:103–109

    Article  PubMed  CAS  Google Scholar 

  123. Elliot KA, Rosenfeld M (1958) Anaerobic glycolysis in brain slices after deprivation of oxygen and glucose. Can J Biochem Physiol 36:721–730

    Article  PubMed  CAS  Google Scholar 

  124. Goldberg WJ, Kadingo RM, Barrett JN (1986) Effects of ischemia-like conditions on cultured neurons: protection by low Na+, low Ca2+ solutions. J Neurosci 6:3144–3151

    PubMed  CAS  Google Scholar 

  125. Dugan LL, Kim-Han JS (2004) Astrocyte mitochondria in in vitro models of ischemia. J Bioenerg Biomembr 36:317–321

    Article  PubMed  CAS  Google Scholar 

  126. Xu L, Sapolsky RM, Giffard RG (2001) Differential sensitivity of murine astrocytes and neurons from different brain regions to injury. Exp Neurol 169:416–424

    Article  PubMed  CAS  Google Scholar 

  127. Almeida A, Delgado-Esteban M, Bolanos JP et al (2002) Oxygen and glucose deprivation induces mitochondrial dysfunction and oxidative stress in neurones but not in astrocytes in primary culture. J Neurochem 81:207–217

    Article  PubMed  CAS  Google Scholar 

  128. Ouyang YB, Xu LJ, Sun YJ et al (2006) Overexpression of inducible heat shock protein 70 and its mutants in astrocytes is associated with maintenance of mitochondrial physiology during glucose deprivation stress. Cell Stress Chaperones 11:180–186

    Article  PubMed  CAS  Google Scholar 

  129. Badawi Y, Ramamoorthy P, Shi H (2012) Hypoxia inducible factor 1 protects hypoxic astrocytes against glutamate toxicity. ASN Neuro 4:231–241

    Google Scholar 

  130. Vangeison G, Carr D, Federoff HJ et al (2008) The good, the bad, and the cell type-specific roles of hypoxia inducible factor-1 alpha in neurons and astrocytes. J Neurosci 28:1988–1993

    Article  PubMed  CAS  Google Scholar 

  131. Bondarenko A, Chesler M (2001) Calcium dependence of rapid astrocyte death induced by transient hypoxia, acidosis, and extracellular ion shifts. Glia 34:143–149

    Article  PubMed  CAS  Google Scholar 

  132. Maloney-Wilensky E, Gracias V, Itkin A et al (2009) Brain tissue oxygen and outcome after severe traumatic brain injury: a systematic review. Crit Care Med 37:2057–2063

    Article  PubMed  Google Scholar 

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Acknowledgements

This work was supported by Swedish Research Council (11548 to MPy, 20116 to MPa), ALF Gothenburg (11267 to MPa and 146051 to MPy), STENA Foundation, AFA Insurance, the EU projects EduGlia (237956 to MPy), TargetBraIn (279017 to MPy) and NanoNet COST Action (BM1002), and R. and T. Söderberg’s, E. Jacobson’s, and R. and U. Amlöv’s Foundations.

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Pekny, M., Porritt, M., de Pablo, Y., Pekna, M., Wilhelmsson, U. (2013). Reactive Astrocytes, Astrocyte Intermediate Filament Proteins, and Their Role in the Disease Pathogenesis. In: Dermietzel, R. (eds) The Cytoskeleton. Neuromethods, vol 79. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-266-7_13

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  • DOI: https://doi.org/10.1007/978-1-62703-266-7_13

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