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Extracellular Matrix in Stroke

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Book cover Cerebral Ischemic Reperfusion Injuries (CIRI)

Part of the book series: Springer Series in Translational Stroke Research ((SSTSR))

Abstract

The extracellular matrix (ECM) is a non-cellular structure found in all tissues. It undergoes tightly controlled remodeling in both physiological (e.g., during development and upon adaption to physiological needs) and pathological conditions, and exerts diverse and important functions. After stroke, the structure of ECM is disrupted and the expression of ECM proteins is altered. The significance of these changes, however, remains largely unknown, mainly due to the intrinsic complexity of the ECM. In this chapter, I first introduce the three types of ECM in the brain with a focus on the basement membranes (BMs). Next, BM assembly and function are briefly summarized. Third, BM changes in stroke are discussed in detail. Furthermore, important questions that need to be answered in future studies are described.

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References

  1. Bignami A, Hosley M, Dahl D. Hyaluronic acid and hyaluronic acid-binding proteins in brain extracellular matrix. Anat Embryol (Berl). 1993;188:419–33.

    Article  CAS  Google Scholar 

  2. Cragg B. Brain extracellular space fixed for electron microscopy. Neurosci Lett. 1979;15:301–6.

    Article  PubMed  CAS  Google Scholar 

  3. Hynes RO. The extracellular matrix: not just pretty fibrils. Science. 2009;326:1216–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Baeten KM, Akassoglou K. Extracellular matrix and matrix receptors in blood-brain barrier formation and stroke. Dev Neurobiol. 2011;71:1018–39.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Jarvelainen H, Sainio A, Koulu M, Wight TN, Penttinen R. Extracellular matrix molecules: potential targets in pharmacotherapy. Pharmacol Rev. 2009;61:198–223.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Bateman JF, Boot-Handford RP, Lamande SR. Genetic diseases of connective tissues: cellular and extracellular effects of ecm mutations. Nat Rev Genet. 2009;10:173–83.

    Article  PubMed  CAS  Google Scholar 

  7. Yao Y. Laminin: loss-of-function studies. Cell Mol Life Sci. 2017;74(6):1095–115.

    Article  PubMed  CAS  Google Scholar 

  8. Rauch U. Brain matrix: structure, turnover and necessity. Biochem Soc Trans. 2007;35:656–60.

    Article  PubMed  CAS  Google Scholar 

  9. Lau LW, Cua R, Keough MB, Haylock-Jacobs S, Yong VW. Pathophysiology of the brain extracellular matrix: a new target for remyelination. Nat Rev Neurosci. 2013;14:722–9.

    Article  PubMed  CAS  Google Scholar 

  10. Bonnans C, Chou J, Werb Z. Remodelling the extracellular matrix in development and disease. Nat Rev Mol Cell Biol. 2014;15:786–801.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Kwok JC, Dick G, Wang D, Fawcett JW. Extracellular matrix and perineuronal nets in cns repair. Dev Neurobiol. 2011;71:1073–89.

    Article  PubMed  CAS  Google Scholar 

  12. Bonneh-Barkay D, Wiley CA. Brain extracellular matrix in neurodegeneration. Brain Pathol. 2009;19:573–85.

    Article  PubMed  CAS  Google Scholar 

  13. Yamaguchi Y. Lecticans: organizers of the brain extracellular matrix. Cell Mol Life Sci. 2000;57:276–89.

    Article  PubMed  CAS  Google Scholar 

  14. Dityatev A, Schachner M. Extracellular matrix molecules and synaptic plasticity. Nat Rev Neurosci. 2003;4:456–68.

    Article  PubMed  CAS  Google Scholar 

  15. Vracko R. Significance of basal lamina for regeneration of injured lung. Virchows Arch A Pathol Pathol Anat. 1972;355:264–74.

    Article  PubMed  CAS  Google Scholar 

  16. Vracko R, Benditt EP. Basal lamina: the scaffold for orderly cell replacement. Observations on regeneration of injured skeletal muscle fibers and capillaries. J Cell Biol. 1972;55:406–19.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Vracko R, Benditt EP. Capillary basal lamina thickening. Its relationship to endothelial cell death and replacement. J Cell Biol. 1970;47:281–5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Vracko R. Basal lamina scaffold-anatomy and significance for maintenance of orderly tissue structure. Am J Pathol. 1974;77:314–46.

    PubMed  CAS  Google Scholar 

  19. Vracko R, Strandness DE Jr. Basal lamina of abdominal skeletal muscle capillaries in diabetics and nondiabetics. Circulation. 1967;35:690–700.

    Article  PubMed  CAS  Google Scholar 

  20. Ruben GC, Yurchenco PD. High resolution platinum-carbon replication of freeze-dried basement membrane. Microsc Res Tech. 1994;28:13–28.

    Article  PubMed  CAS  Google Scholar 

  21. Yurchenco PD, Amenta PS, Patton BL. Basement membrane assembly, stability and activities observed through a developmental lens. Matrix Biol. 2004;22:521–38.

    Article  PubMed  CAS  Google Scholar 

  22. Kalluri R. Basement membranes: structure, assembly and role in tumour angiogenesis. Nat Rev Cancer. 2003;3:422–33.

    Article  PubMed  CAS  Google Scholar 

  23. Sorokin L. The impact of the extracellular matrix on inflammation. Nat Rev Immunol. 2010;10:712–23.

    Article  PubMed  CAS  Google Scholar 

  24. Hallmann R, Zhang X, Di Russo J, Li L, Song J, Hannocks MJ, et al. The regulation of immune cell trafficking by the extracellular matrix. Curr Opin Cell Biol. 2015;36:54–61.

    Article  PubMed  CAS  Google Scholar 

  25. Paulsson M. Basement membrane proteins: Structure, assembly, and cellular interactions. Crit Rev Biochem Mol Biol. 1992;27:93–127.

    Article  PubMed  CAS  Google Scholar 

  26. Yurchenco PD, Schittny JC. Molecular architecture of basement membranes. FASEB J. 1990;4:1577–90.

    Article  PubMed  CAS  Google Scholar 

  27. Schittny JC, Yurchenco PD. Basement membranes: molecular organization and function in development and disease. Curr Opin Cell Biol. 1989;1:983–8.

    Article  PubMed  CAS  Google Scholar 

  28. Erickson AC, Couchman JR. Still more complexity in mammalian basement membranes. J Histochem Cytochem. 2000;48:1291–306.

    Article  PubMed  CAS  Google Scholar 

  29. Myers JC, Dion AS, Abraham V, Amenta PS. Type xv collagen exhibits a widespread distribution in human tissues but a distinct localization in basement membrane zones. Cell Tissue Res. 1996;286:493–505.

    Article  PubMed  CAS  Google Scholar 

  30. Myers JC, Li D, Bageris A, Abraham V, Dion AS, Amenta PS. Biochemical and immunohistochemical characterization of human type xix defines a novel class of basement membrane zone collagens. Am J Pathol. 1997;151:1729–40.

    PubMed  PubMed Central  CAS  Google Scholar 

  31. Saarela J, Rehn M, Oikarinen A, Autio-Harmainen H, Pihlajaniemi T. The short and long forms of type xviii collagen show clear tissue specificities in their expression and location in basement membrane zones in humans. Am J Pathol. 1998;153:611–26.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Tomono Y, Naito I, Ando K, Yonezawa T, Sado Y, Hirakawa S, et al. Epitope-defined monoclonal antibodies against multiplexin collagens demonstrate that type xv and xviii collagens are expressed in specialized basement membranes. Cell Struct Funct. 2002;27:9–20.

    Article  PubMed  CAS  Google Scholar 

  33. Yurchenco PD. Basement membranes: cell scaffoldings and signaling platforms. Cold Spring Harb Perspect Biol. 2011;3:pii: a004911.

    Article  CAS  Google Scholar 

  34. Martin GR, Timpl R. Laminin and other basement membrane components. Annu Rev Cell Biol. 1987;3:57–85.

    Article  PubMed  CAS  Google Scholar 

  35. Sixt M, Engelhardt B, Pausch F, Hallmann R, Wendler O, Sorokin LM. Endothelial cell laminin isoforms, laminins 8 and 10, play decisive roles in t cell recruitment across the blood-brain barrier in experimental autoimmune encephalomyelitis. J Cell Biol. 2001;153:933–46.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Hallmann R, Horn N, Selg M, Wendler O, Pausch F, Sorokin LM. Expression and function of laminins in the embryonic and mature vasculature. Physiol Rev. 2005;85:979–1000.

    Article  CAS  PubMed  Google Scholar 

  37. Owens T, Bechmann I, Engelhardt B. Perivascular spaces and the two steps to neuroinflammation. J Neuropathol Exp Neurol. 2008;67:1113–21.

    Article  PubMed  Google Scholar 

  38. van Horssen J, Bo L, Vos CM, Virtanen I, de Vries HE. Basement membrane proteins in multiple sclerosis-associated inflammatory cuffs: potential role in influx and transport of leukocytes. J Neuropathol Exp Neurol. 2005;64:722–9.

    Article  PubMed  Google Scholar 

  39. Hudson BG, Reeders ST, Tryggvason K. Type iv collagen: structure, gene organization, and role in human diseases. Molecular basis of goodpasture and alport syndromes and diffuse leiomyomatosis. J Biol Chem. 1993;268:26033–6.

    PubMed  CAS  Google Scholar 

  40. Kalluri R. Discovery of type iv collagen non-collagenous domains as novel integrin ligands and endogenous inhibitors of angiogenesis. Cold Spring Harb Symp Quant Biol. 2002;67:255–66.

    Article  PubMed  CAS  Google Scholar 

  41. Filie JD, Burbelo PD, Kozak CA. Genetic mapping of the alpha 1 and alpha 2 (iv) collagen genes to mouse chromosome 8. Mamm Genome. 1995;6:487.

    Article  PubMed  CAS  Google Scholar 

  42. Sugimoto M, Oohashi T, Ninomiya Y. The genes col4a5 and col4a6, coding for basement membrane collagen chains alpha 5(iv) and alpha 6(iv), are located head-to-head in close proximity on human chromosome xq22 and col4a6 is transcribed from two alternative promoters. Proc Natl Acad Sci U S A. 1994;91:11679–83.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Soininen R, Huotari M, Hostikka SL, Prockop DJ, Tryggvason K. The structural genes for alpha 1 and alpha 2 chains of human type iv collagen are divergently encoded on opposite DNA strands and have an overlapping promoter region. J Biol Chem. 1988;263:17217–20.

    PubMed  CAS  Google Scholar 

  44. Momota R, Sugimoto M, Oohashi T, Kigasawa K, Yoshioka H, Ninomiya Y. Two genes, col4a3 and col4a4 coding for the human alpha3(iv) and alpha4(iv) collagen chains are arranged head-to-head on chromosome 2q36. FEBS Lett. 1998;424:11–6.

    Article  PubMed  CAS  Google Scholar 

  45. Ortega N, Werb Z. New functional roles for non-collagenous domains of basement membrane collagens. J Cell Sci. 2002;115:4201–14.

    Article  PubMed  CAS  Google Scholar 

  46. Khoshnoodi J, Pedchenko V, Hudson BG. Mammalian collagen iv. Microsc Res Tech. 2008;71:357–70.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Vanacore RM, Shanmugasundararaj S, Friedman DB, Bondar O, Hudson BG, Sundaramoorthy M. The alpha1.Alpha2 network of collagen iv. Reinforced stabilization of the noncollagenous domain-1 by noncovalent forces and the absence of met-lys cross-links. J Biol Chem. 2004;279:44723–30.

    Article  PubMed  CAS  Google Scholar 

  48. Tilling T, Korte D, Hoheisel D, Galla HJ. Basement membrane proteins influence brain capillary endothelial barrier function in vitro. J Neurochem. 1998;71:1151–7.

    Article  PubMed  CAS  Google Scholar 

  49. Poschl E, Schlotzer-Schrehardt U, Brachvogel B, Saito K, Ninomiya Y, Mayer U. Collagen iv is essential for basement membrane stability but dispensable for initiation of its assembly during early development. Development. 2004;131:1619–28.

    Article  PubMed  CAS  Google Scholar 

  50. Kuo DS, Labelle-Dumais C, Mao M, Jeanne M, Kauffman WB, Allen J, et al. Allelic heterogeneity contributes to variability in ocular dysgenesis, myopathy and brain malformations caused by col4a1 and col4a2 mutations. Hum Mol Genet. 2014;23:1709–22.

    Article  PubMed  CAS  Google Scholar 

  51. Favor J, Gloeckner CJ, Janik D, Klempt M, Neuhauser-Klaus A, Pretsch W, et al. Type iv procollagen missense mutations associated with defects of the eye, vascular stability, the brain, kidney function and embryonic or postnatal viability in the mouse, mus musculus: an extension of the col4a1 allelic series and the identification of the first two col4a2 mutant alleles. Genetics. 2007;175:725–36.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Jeanne M, Jorgensen J, Gould DB. Molecular and genetic analyses of collagen type iv mutant mouse models of spontaneous intracerebral hemorrhage identify mechanisms for stroke prevention. Circulation. 2015;131:1555–65.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Miner JH, Yurchenco PD. Laminin functions in tissue morphogenesis. Annu Rev Cell Dev Biol. 2004;20:255–84.

    Article  PubMed  CAS  Google Scholar 

  54. Domogatskaya A, Rodin S, Tryggvason K. Functional diversity of laminins. Annu Rev Cell Dev Biol. 2012;28:523–53.

    Article  PubMed  CAS  Google Scholar 

  55. Colognato H, Yurchenco PD. Form and function: the laminin family of heterotrimers. Dev Dyn. 2000;218:213–34.

    Article  PubMed  CAS  Google Scholar 

  56. Aumailley M. The laminin family. Cell Adhes Migr. 2013;7:48–55.

    Article  Google Scholar 

  57. Aumailley M, Bruckner-Tuderman L, Carter WG, Deutzmann R, Edgar D, Ekblom P, et al. A simplified laminin nomenclature. Matrix Biol. 2005;24:326–32.

    Article  PubMed  CAS  Google Scholar 

  58. Durbeej M. Laminins. Cell Tissue Res. 2010;339:259–68.

    Article  PubMed  CAS  Google Scholar 

  59. McKee KK, Harrison D, Capizzi S, Yurchenco PD. Role of laminin terminal globular domains in basement membrane assembly. J Biol Chem. 2007;282:21437–47.

    Article  PubMed  CAS  Google Scholar 

  60. Burgeson RE, Chiquet M, Deutzmann R, Ekblom P, Engel J, Kleinman H, et al. A new nomenclature for the laminins. Matrix Biol. 1994;14:209–11.

    Article  PubMed  CAS  Google Scholar 

  61. Sorokin LM, Pausch F, Frieser M, Kroger S, Ohage E, Deutzmann R. Developmental regulation of the laminin alpha5 chain suggests a role in epithelial and endothelial cell maturation. Dev Biol. 1997;189:285–300.

    Article  PubMed  CAS  Google Scholar 

  62. Jucker M, Tian M, Norton DD, Sherman C, Kusiak JW. Laminin alpha 2 is a component of brain capillary basement membrane: reduced expression in dystrophic dy mice. Neuroscience. 1996;71:1153–61.

    Article  PubMed  CAS  Google Scholar 

  63. Gautam J, Zhang X, Yao Y. The role of pericytic laminin in blood brain barrier integrity maintenance. Sci Rep. 2016;6:36450.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Yao Y, Chen ZL, Norris EH, Strickland S. Astrocytic laminin regulates pericyte differentiation and maintains blood brain barrier integrity. Nat Commun. 2014;5:3413.

    Article  PubMed  CAS  Google Scholar 

  65. Thyboll J, Kortesmaa J, Cao R, Soininen R, Wang L, Iivanainen A, et al. Deletion of the laminin alpha4 chain leads to impaired microvessel maturation. Mol Cell Biol. 2002;22:1194–202.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  66. Patton BL, Miner JH, Chiu AY, Sanes JR. Distribution and function of laminins in the neuromuscular system of developing, adult, and mutant mice. J Cell Biol. 1997;139:1507–21.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. Miner JH, Li C, Mudd JL, Go G, Sutherland AE. Compositional and structural requirements for laminin and basement membranes during mouse embryo implantation and gastrulation. Development. 2004;131:2247–56.

    Article  PubMed  CAS  Google Scholar 

  68. Alpy F, Jivkov I, Sorokin L, Klein A, Arnold C, Huss Y, et al. Generation of a conditionally null allele of the laminin alpha1 gene. Genesis. 2005;43:59–70.

    Article  PubMed  CAS  Google Scholar 

  69. Smyth N, Vatansever HS, Murray P, Meyer M, Frie C, Paulsson M, et al. Absence of basement membranes after targeting the lamc1 gene results in embryonic lethality due to failure of endoderm differentiation. J Cell Biol. 1999;144:151–60.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. Murray P, Edgar D. Regulation of programmed cell death by basement membranes in embryonic development. J Cell Biol. 2000;150:1215–21.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. Kang SH, Kramer JM. Nidogen is nonessential and not required for normal type iv collagen localization in caenorhabditis elegans. Mol Biol Cell. 2000;11:3911–23.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. Murshed M, Smyth N, Miosge N, Karolat J, Krieg T, Paulsson M, et al. The absence of nidogen 1 does not affect murine basement membrane formation. Mol Cell Biol. 2000;20:7007–12.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  73. Dong L, Chen Y, Lewis M, Hsieh JC, Reing J, Chaillet JR, et al. Neurologic defects and selective disruption of basement membranes in mice lacking entactin-1/nidogen-1. Lab Investig. 2002;82:1617–30.

    Article  PubMed  CAS  Google Scholar 

  74. May CA. Distribution of nidogen in the murine eye and ocular phenotype of the nidogen-1 knockout mouse. ISRN Ophthalmol. 2012;2012:378641.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Schymeinsky J, Nedbal S, Miosge N, Poschl E, Rao C, Beier DR, et al. Gene structure and functional analysis of the mouse nidogen-2 gene: Nidogen-2 is not essential for basement membrane formation in mice. Mol Cell Biol. 2002;22:6820–30.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  76. Miosge N, Sasaki T, Timpl R. Evidence of nidogen-2 compensation for nidogen-1 deficiency in transgenic mice. Matrix Biol. 2002;21:611–21.

    Article  PubMed  CAS  Google Scholar 

  77. Bader BL, Smyth N, Nedbal S, Miosge N, Baranowsky A, Mokkapati S, et al. Compound genetic ablation of nidogen 1 and 2 causes basement membrane defects and perinatal lethality in mice. Mol Cell Biol. 2005;25:6846–56.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  78. Bose K, Nischt R, Page A, Bader BL, Paulsson M, Smyth N. Loss of nidogen-1 and -2 results in syndactyly and changes in limb development. J Biol Chem. 2006;281:39620–9.

    Article  PubMed  CAS  Google Scholar 

  79. Mokkapati S, Baranowsky A, Mirancea N, Smyth N, Breitkreutz D, Nischt R. Basement membranes in skin are differently affected by lack of nidogen 1 and 2. J Invest Dermatol. 2008;128:2259–67.

    Article  PubMed  CAS  Google Scholar 

  80. Knox SM, Whitelock JM. Perlecan: how does one molecule do so many things? Cell Mol Life Sci. 2006;63:2435–45.

    Article  PubMed  CAS  Google Scholar 

  81. Farach-Carson MC, Carson DD. Perlecan—a multifunctional extracellular proteoglycan scaffold. Glycobiology. 2007;17:897–905.

    Article  PubMed  CAS  Google Scholar 

  82. Whitelock JM, Melrose J, Iozzo RV. Diverse cell signaling events modulated by perlecan. Biochemistry. 2008;47:11174–83.

    Article  PubMed  CAS  Google Scholar 

  83. Roberts J, Kahle MP, Bix GJ. Perlecan and the blood-brain barrier: beneficial proteolysis? Front Pharmacol. 2012;3:155.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  84. Costell M, Sasaki T, Mann K, Yamada Y, Timpl R. Structural characterization of recombinant domain ii of the basement membrane proteoglycan perlecan. FEBS Lett. 1996;396:127–31.

    Article  PubMed  CAS  Google Scholar 

  85. Crossin KL, Krushel LA. Cellular signaling by neural cell adhesion molecules of the immunoglobulin superfamily. Dev Dyn. 2000;218:260–79.

    Article  PubMed  CAS  Google Scholar 

  86. Dolan M, Horchar T, Rigatti B, Hassell JR. Identification of sites in domain i of perlecan that regulate heparan sulfate synthesis. J Biol Chem. 1997;272:4316–22.

    Article  PubMed  CAS  Google Scholar 

  87. Fjeldstad K, Kolset SO. Decreasing the metastatic potential in cancers—targeting the heparan sulfate proteoglycans. Curr Drug Targets. 2005;6:665–82.

    Article  PubMed  CAS  Google Scholar 

  88. Hopf M, Gohring W, Mann K, Timpl R. Mapping of binding sites for nidogens, fibulin-2, fibronectin and heparin to different ig modules of perlecan. J Mol Biol. 2001;311:529–41.

    Article  PubMed  CAS  Google Scholar 

  89. Jiang X, Couchman JR. Perlecan and tumor angiogenesis. J Histochem Cytochem. 2003;51:1393–410.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  90. Merz DC, Alves G, Kawano T, Zheng H, Culotti JG. Unc-52/perlecan affects gonadal leader cell migrations in C. elegans hermaphrodites through alterations in growth factor signaling. Dev Biol. 2003;256:173–86.

    Article  PubMed  CAS  Google Scholar 

  91. Yang Y. Wnts and wing: Wnt signaling in vertebrate limb development and musculoskeletal morphogenesis. Birth Defects Res C Embryo Today. 2003;69:305–17.

    Article  PubMed  CAS  Google Scholar 

  92. Gonzalez EM, Reed CC, Bix G, Fu J, Zhang Y, Gopalakrishnan B, et al. Bmp-1/tolloid-like metalloproteases process endorepellin, the angiostatic c-terminal fragment of perlecan. J Biol Chem. 2005;280:7080–7.

    Article  PubMed  CAS  Google Scholar 

  93. Saini MG, Bix GJ. Oxygen-glucose deprivation (ogd) and interleukin-1 (il-1) differentially modulate cathepsin b/l mediated generation of neuroprotective perlecan lg3 by neurons. Brain Res. 2012;1438:65–74.

    Article  PubMed  CAS  Google Scholar 

  94. Whitelock JM, Murdoch AD, Iozzo RV, Underwood PA. The degradation of human endothelial cell-derived perlecan and release of bound basic fibroblast growth factor by stromelysin, collagenase, plasmin, and heparanases. J Biol Chem. 1996;271:10079–86.

    Article  PubMed  CAS  Google Scholar 

  95. Bix G, Fu J, Gonzalez EM, Macro L, Barker A, Campbell S, et al. Endorepellin causes endothelial cell disassembly of actin cytoskeleton and focal adhesions through alpha2beta1 integrin. J Cell Biol. 2004;166:97–109.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  96. Irving-Rodgers HF, Catanzariti KD, Aspden WJ, D'Occhio MJ, Rodgers RJ. Remodeling of extracellular matrix at ovulation of the bovine ovarian follicle. Mol Reprod Dev. 2006;73:1292–302.

    Article  PubMed  CAS  Google Scholar 

  97. Thadikkaran L, Crettaz D, Siegenthaler MA, Gallot D, Sapin V, Iozzo RV, et al. The role of proteomics in the assessment of premature rupture of fetal membranes. Clin Chim Acta. 2005;360:27–36.

    Article  PubMed  CAS  Google Scholar 

  98. Lee B, Clarke D, Al Ahmad A, Kahle M, Parham C, Auckland L, et al. Perlecan domain v is neuroprotective and proangiogenic following ischemic stroke in rodents. J Clin Invest. 2011;121:3005–23.

    Article  PubMed  PubMed Central  Google Scholar 

  99. Saini MG, Pinteaux E, Lee B, Bix GJ. Oxygen-glucose deprivation and interleukin-1alpha trigger the release of perlecan lg3 by cells of neurovascular unit. J Neurochem. 2011;119:760–71.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  100. Arikawa-Hirasawa E, Watanabe H, Takami H, Hassell JR, Yamada Y. Perlecan is essential for cartilage and cephalic development. Nat Genet. 1999;23:354–8.

    Article  PubMed  CAS  Google Scholar 

  101. Costell M, Gustafsson E, Aszodi A, Morgelin M, Bloch W, Hunziker E, et al. Perlecan maintains the integrity of cartilage and some basement membranes. J Cell Biol. 1999;147:1109–22.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  102. Rossi M, Morita H, Sormunen R, Airenne S, Kreivi M, Wang L, et al. Heparan sulfate chains of perlecan are indispensable in the lens capsule but not in the kidney. EMBO J. 2003;22:236–45.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  103. Mouw JK, Ou G, Weaver VM. Extracellular matrix assembly: a multiscale deconstruction. Nat Rev Mol Cell Biol. 2014;15:771–85.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  104. Takagi J, Yang Y, Liu JH, Wang JH, Springer TA. Complex between nidogen and laminin fragments reveals a paradigmatic beta-propeller interface. Nature. 2003;424:969–74.

    Article  PubMed  CAS  Google Scholar 

  105. Willem M, Miosge N, Halfter W, Smyth N, Jannetti I, Burghart E, et al. Specific ablation of the nidogen-binding site in the laminin gamma1 chain interferes with kidney and lung development. Development. 2002;129:2711–22.

    PubMed  CAS  Google Scholar 

  106. Aumailley M, Pesch M, Tunggal L, Gaill F, Fassler R. Altered synthesis of laminin 1 and absence of basement membrane component deposition in (beta)1 integrin-deficient embryoid bodies. J Cell Sci. 2000;113(Pt 2):259–68.

    PubMed  CAS  Google Scholar 

  107. Tsiper MV, Yurchenco PD. Laminin assembles into separate basement membrane and fibrillar matrices in schwann cells. J Cell Sci. 2002;115:1005–15.

    PubMed  CAS  Google Scholar 

  108. Charonis AS, Tsilibary EC, Yurchenco PD, Furthmayr H. Binding of laminin to type iv collagen: a morphological study. J Cell Biol. 1985;100:1848–53.

    Article  PubMed  CAS  Google Scholar 

  109. Sasaki T, Forsberg E, Bloch W, Addicks K, Fassler R, Timpl R. Deficiency of beta 1 integrins in teratoma interferes with basement membrane assembly and laminin-1 expression. Exp Cell Res. 1998;238:70–81.

    Article  PubMed  CAS  Google Scholar 

  110. Di Russo J, Hannocks MJ, Luik AL, Song J, Zhang X, Yousif L, et al. Vascular laminins in physiology and pathology. In: Matrix Biol, vol. 57-58; 2017. p. 140–8.

    Google Scholar 

  111. Engelhardt B, Ransohoff RM. Capture, crawl, cross: the T cell code to breach the blood-brain barriers. Trends Immunol. 2012;33:579–89.

    Article  PubMed  CAS  Google Scholar 

  112. Zlokovic BV. The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron. 2008;57:178–201.

    Article  PubMed  CAS  Google Scholar 

  113. Furie MB, Naprstek BL, Silverstein SC. Migration of neutrophils across monolayers of cultured microvascular endothelial cells. An in vitro model of leucocyte extravasation. J Cell Sci. 1987;88(Pt 2):161–75.

    PubMed  CAS  Google Scholar 

  114. Hurley JV. An electron microscopic study of leucocytic emigration and vascular permeability in rat skin. Aust J Exp Biol Med Sci. 1963;41:171–86.

    Article  PubMed  CAS  Google Scholar 

  115. Marchesi VT, Florey HW. Electron micrographic observations on the emigration of leucocytes. Q J Exp Physiol Cogn Med Sci. 1960;45:343–8.

    PubMed  CAS  Google Scholar 

  116. Ohashi KL, Tung DK, Wilson J, Zweifach BW, Schmid-Schonbein GW. Transvascular and interstitial migration of neutrophils in rat mesentery. Microcirculation. 1996;3:199–210.

    Article  PubMed  CAS  Google Scholar 

  117. Hoshi O, Ushiki T. Neutrophil extravasation in rat mesenteric venules induced by the chemotactic peptide n-formyl-methionyl-luecylphenylalanine (fmlp), with special attention to a barrier function of the vascular basal lamina for neutrophil migration. Arch Histol Cytol. 2004;67:107–14.

    Article  PubMed  CAS  Google Scholar 

  118. Yadav R, Larbi KY, Young RE, Nourshargh S. Migration of leukocytes through the vessel wall and beyond. Thromb Haemost. 2003;90:598–606.

    PubMed  CAS  Google Scholar 

  119. Bixel MG, Petri B, Khandoga AG, Khandoga A, Wolburg-Buchholz K, Wolburg H, et al. A cd99-related antigen on endothelial cells mediates neutrophil but not lymphocyte extravasation in vivo. Blood. 2007;109:5327–36.

    Article  PubMed  CAS  Google Scholar 

  120. Bartholomaus I, Kawakami N, Odoardi F, Schlager C, Miljkovic D, Ellwart JW, et al. Effector t cell interactions with meningeal vascular structures in nascent autoimmune cns lesions. Nature. 2009;462:94–8.

    Article  PubMed  CAS  Google Scholar 

  121. Writing Group M, Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, et al. Heart disease and stroke statistics-2016 update: a report from the american heart association. Circulation. 2016;133:e38–60.

    Article  Google Scholar 

  122. Hamann GF, Burggraf D, Martens HK, Liebetrau M, Jager G, Wunderlich N, et al. Mild to moderate hypothermia prevents microvascular basal lamina antigen loss in experimental focal cerebral ischemia. Stroke. 2004;35:764–9.

    Article  PubMed  Google Scholar 

  123. Yepes M, Sandkvist M, Wong MK, Coleman TA, Smith E, Cohan SL, et al. Neuroserpin reduces cerebral infarct volume and protects neurons from ischemia-induced apoptosis. Blood. 2000;96:569–76.

    PubMed  CAS  Google Scholar 

  124. Nahirney PC, Reeson P, Brown CE. Ultrastructural analysis of blood-brain barrier breakdown in the peri-infarct zone in young adult and aged mice. J Cereb Blood Flow Metab. 2016;36:413–25.

    Article  PubMed  Google Scholar 

  125. Kwon I, Kim EH, del Zoppo GJ, Heo JH. Ultrastructural and temporal changes of the microvascular basement membrane and astrocyte interface following focal cerebral ischemia. J Neurosci Res. 2009;87:668–76.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  126. Wang CX, Shuaib A. Critical role of microvasculature basal lamina in ischemic brain injury. Prog Neurobiol. 2007;83:140–8.

    Article  PubMed  CAS  Google Scholar 

  127. Scholler K, Trinkl A, Klopotowski M, Thal SC, Plesnila N, Trabold R, et al. Characterization of microvascular basal lamina damage and blood-brain barrier dysfunction following subarachnoid hemorrhage in rats. Brain Res. 2007;1142:237–46.

    Article  PubMed  CAS  Google Scholar 

  128. Wang J, Tsirka SE. Tuftsin fragment 1–3 is beneficial when delivered after the induction of intracerebral hemorrhage. Stroke. 2005;36:613–8.

    Article  PubMed  CAS  Google Scholar 

  129. Wang J, Rogove AD, Tsirka AE, Tsirka SE. Protective role of tuftsin fragment 1–3 in an animal model of intracerebral hemorrhage. Ann Neurol. 2003;54:655–64.

    Article  PubMed  CAS  Google Scholar 

  130. Wang J, Tsirka SE. Contribution of extracellular proteolysis and microglia to intracerebral hemorrhage. Neurocrit Care. 2005;3:77–85.

    Article  PubMed  CAS  Google Scholar 

  131. Jeanne M, Labelle-Dumais C, Jorgensen J, Kauffman WB, Mancini GM, Favor J, et al. Col4a2 mutations impair col4a1 and col4a2 secretion and cause hemorrhagic stroke. Am J Hum Genet. 2012;90:91–101.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  132. Hynes RO. Stretching the boundaries of extracellular matrix research. Nat Rev Mol Cell Biol. 2014;15:761–3.

    Article  PubMed  CAS  Google Scholar 

  133. Yepes M, Sandkvist M, Moore EG, Bugge TH, Strickland DK, Lawrence DA. Tissue-type plasminogen activator induces opening of the blood-brain barrier via the ldl receptor-related protein. J Clin Invest. 2003;112:1533–40.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  134. Ahn MY, Zhang ZG, Tsang W, Chopp M. Endogenous plasminogen activator expression after embolic focal cerebral ischemia in mice. Brain Res. 1999;837:169–76.

    Article  PubMed  CAS  Google Scholar 

  135. Hosomi N, Lucero J, Heo JH, Koziol JA, Copeland BR, del Zoppo GJ. Rapid differential endogenous plasminogen activator expression after acute middle cerebral artery occlusion. Stroke. 2001;32:1341–8.

    Article  PubMed  CAS  Google Scholar 

  136. Wang CX, Yang T, Shuaib A. Clot fragments formed from original thrombus obstruct downstream arteries in the ischemic injured brain. Microcirculation. 2006;13:229–36.

    Article  PubMed  CAS  Google Scholar 

  137. Liotta LA, Goldfarb RH, Brundage R, Siegal GP, Terranova V, Garbisa S. Effect of plasminogen activator (urokinase), plasmin, and thrombin on glycoprotein and collagenous components of basement membrane. Cancer Res. 1981;41:4629–36.

    PubMed  CAS  Google Scholar 

  138. Hamann GF, Liebetrau M, Martens H, Burggraf D, Kloss CU, Bultemeier G, et al. Microvascular basal lamina injury after experimental focal cerebral ischemia and reperfusion in the rat. J Cereb Blood Flow Metab. 2002;22:526–33.

    Article  PubMed  Google Scholar 

  139. Lijnen HR, Van Hoef B, Lupu F, Moons L, Carmeliet P, Collen D. Function of the plasminogen/plasmin and matrix metalloproteinase systems after vascular injury in mice with targeted inactivation of fibrinolytic system genes. Arterioscler Thromb Vasc Biol. 1998;18:1035–45.

    Article  PubMed  CAS  Google Scholar 

  140. Cunningham LA, Wetzel M, Rosenberg GA. Multiple roles for mmps and timps in cerebral ischemia. Glia. 2005;50:329–39.

    Article  PubMed  Google Scholar 

  141. Fujimura M, Gasche Y, Morita-Fujimura Y, Massengale J, Kawase M, Chan PH. Early appearance of activated matrix metalloproteinase-9 and blood-brain barrier disruption in mice after focal cerebral ischemia and reperfusion. Brain Res. 1999;842:92–100.

    Article  PubMed  CAS  Google Scholar 

  142. Gasche Y, Fujimura M, Morita-Fujimura Y, Copin JC, Kawase M, Massengale J, et al. Early appearance of activated matrix metalloproteinase-9 after focal cerebral ischemia in mice: a possible role in blood-brain barrier dysfunction. J Cereb Blood Flow Metab. 1999;19:1020–8.

    Article  PubMed  CAS  Google Scholar 

  143. Heo JH, Lucero J, Abumiya T, Koziol JA, Copeland BR, del Zoppo GJ. Matrix metalloproteinases increase very early during experimental focal cerebral ischemia. J Cereb Blood Flow Metab. 1999;19:624–33.

    Article  PubMed  CAS  Google Scholar 

  144. Romanic AM, White RF, Arleth AJ, Ohlstein EH, Barone FC. Matrix metalloproteinase expression increases after cerebral focal ischemia in rats: Inhibition of matrix metalloproteinase-9 reduces infarct size. Stroke. 1998;29:1020–30.

    Article  PubMed  CAS  Google Scholar 

  145. Petty MA, Wettstein JG. Elements of cerebral microvascular ischaemia. Brain Res Brain Res Rev. 2001;36:23–34.

    Article  PubMed  CAS  Google Scholar 

  146. Liu XS, Zhang ZG, Zhang L, Morris DC, Kapke A, Lu M, et al. Atorvastatin downregulates tissue plasminogen activator-aggravated genes mediating coagulation and vascular permeability in single cerebral endothelial cells captured by laser microdissection. J Cereb Blood Flow Metab. 2006;26:787–96.

    Article  PubMed  CAS  Google Scholar 

  147. Rosenberg GA. Matrix metalloproteinases in neuroinflammation. Glia. 2002;39:279–91.

    Article  PubMed  Google Scholar 

  148. Rosenberg GA, Estrada EY, Dencoff JE. Matrix metalloproteinases and timps are associated with blood-brain barrier opening after reperfusion in rat brain. Stroke. 1998;29:2189–95.

    Article  PubMed  CAS  Google Scholar 

  149. Rosenberg GA, Navratil M, Barone F, Feuerstein G. Proteolytic cascade enzymes increase in focal cerebral ischemia in rat. J Cereb Blood Flow Metab. 1996;16:360–6.

    Article  PubMed  CAS  Google Scholar 

  150. Fukuda S, Fini CA, Mabuchi T, Koziol JA, Eggleston LL Jr, del Zoppo GJ. Focal cerebral ischemia induces active proteases that degrade microvascular matrix. Stroke. 2004;35:998–1004.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  151. Seyfried D, Han Y, Zheng Z, Day N, Moin K, Rempel S, et al. Cathepsin b and middle cerebral artery occlusion in the rat. J Neurosurg. 1997;87:716–23.

    Article  PubMed  CAS  Google Scholar 

  152. Vosko MR, Busch E, Burggraf D, Bultemeier G, Hamann GF. Microvascular basal lamina damage in thromboembolic stroke in a rat model. Neurosci Lett. 2003;353:217–20.

    Article  PubMed  CAS  Google Scholar 

  153. Trinkl A, Vosko MR, Wunderlich N, Dichgans M, Hamann GF. Pravastatin reduces microvascular basal lamina damage following focal cerebral ischemia and reperfusion. Eur J Neurosci. 2006;24:520–6.

    Article  PubMed  Google Scholar 

  154. Breedveld G, de Coo IF, Lequin MH, Arts WF, Heutink P, Gould DB, et al. Novel mutations in three families confirm a major role of col4a1 in hereditary porencephaly. J Med Genet. 2006;43:490–5.

    Article  PubMed  CAS  Google Scholar 

  155. Sibon I, Coupry I, Menegon P, Bouchet JP, Gorry P, Burgelin I, et al. Col4a1 mutation in axenfeld-rieger anomaly with leukoencephalopathy and stroke. Ann Neurol. 2007;62:177–84.

    Article  PubMed  Google Scholar 

  156. Plaisier E, Gribouval O, Alamowitch S, Mougenot B, Prost C, Verpont MC, et al. Col4a1 mutations and hereditary angiopathy, nephropathy, aneurysms, and muscle cramps. N Engl J Med. 2007;357:2687–95.

    Article  PubMed  CAS  Google Scholar 

  157. Anik I, Kokturk S, Genc H, Cabuk B, Koc K, Yavuz S, et al. Immunohistochemical analysis of timp-2 and collagen types i and iv in experimental spinal cord ischemia-reperfusion injury in rats. J Spinal Cord Med. 2011;34:257–64.

    Article  PubMed  PubMed Central  Google Scholar 

  158. Rosell A, Cuadrado E, Ortega-Aznar A, Hernandez-Guillamon M, Lo EH, Montaner J. Mmp-9-positive neutrophil infiltration is associated to blood-brain barrier breakdown and basal lamina type iv collagen degradation during hemorrhagic transformation after human ischemic stroke. Stroke. 2008;39:1121–6.

    Article  PubMed  CAS  Google Scholar 

  159. Gould DB, Phalan FC, Breedveld GJ, van Mil SE, Smith RS, Schimenti JC, et al. Mutations in col4a1 cause perinatal cerebral hemorrhage and porencephaly. Science. 2005;308:1167–71.

    Article  PubMed  CAS  Google Scholar 

  160. Gould DB, Phalan FC, van Mil SE, Sundberg JP, Vahedi K, Massin P, et al. Role of col4a1 in small-vessel disease and hemorrhagic stroke. N Engl J Med. 2006;354:1489–96.

    Article  PubMed  CAS  Google Scholar 

  161. de Vries LS, Mancini GM. Intracerebral hemorrhage and col4a1 and col4a2 mutations, from fetal life into adulthood. Ann Neurol. 2012;71:439–41.

    Article  CAS  PubMed  Google Scholar 

  162. Gunda B, Mine M, Kovacs T, Hornyak C, Bereczki D, Varallyay G, et al. Col4a2 mutation causing adult onset recurrent intracerebral hemorrhage and leukoencephalopathy. J Neurol. 2014;261:500–3.

    Article  PubMed  Google Scholar 

  163. Corlobe A, Tournier-Lasserve E, Mine M, Menjot de Champfleur N, Carra Dalliere C, Ayrignac X, et al. Col4a1 mutation revealed by an isolated brain hemorrhage. Cerebrovasc Dis. 2013;35:593–4.

    Article  PubMed  Google Scholar 

  164. de Vries LS, Koopman C, Groenendaal F, Van Schooneveld M, Verheijen FW, Verbeek E, et al. Col4a1 mutation in two preterm siblings with antenatal onset of parenchymal hemorrhage. Ann Neurol. 2009;65:12–8.

    Article  PubMed  CAS  Google Scholar 

  165. Shah S, Kumar Y, McLean B, Churchill A, Stoodley N, Rankin J, et al. A dominantly inherited mutation in collagen iv a1 (col4a1) causing childhood onset stroke without porencephaly. Eur J Paediatr Neurol. 2010;14:182–7.

    Article  PubMed  Google Scholar 

  166. Lichtenbelt KD, Pistorius LR, De Tollenaer SM, Mancini GM, De Vries LS. Prenatal genetic confirmation of a col4a1 mutation presenting with sonographic fetal intracranial hemorrhage. Ultrasound Obstet Gynecol. 2012;39:726–7.

    Article  PubMed  CAS  Google Scholar 

  167. Garel C, Rosenblatt J, Moutard ML, Heron D, Gelot A, Gonzales M, et al. Fetal intracerebral hemorrhage and col4a1 mutation: promise and uncertainty. Ultrasound Obstet Gynecol. 2013;41:228–30.

    Article  PubMed  CAS  Google Scholar 

  168. Colin E, Sentilhes L, Sarfati A, Mine M, Guichet A, Ploton C, et al. Fetal intracerebral hemorrhage and cataract: Think col4a1. J Perinatol. 2014;34:75–7.

    Article  PubMed  CAS  Google Scholar 

  169. Weng YC, Sonni A, Labelle-Dumais C, de Leau M, Kauffman WB, Jeanne M, et al. Col4a1 mutations in patients with sporadic late-onset intracerebral hemorrhage. Ann Neurol. 2012;71:470–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  170. van der Knaap MS, Smit LM, Barkhof F, Pijnenburg YA, Zweegman S, Niessen HW, et al. Neonatal porencephaly and adult stroke related to mutations in collagen iv a1. Ann Neurol. 2006;59:504–11.

    Article  PubMed  CAS  Google Scholar 

  171. Vahedi K, Massin P, Guichard JP, Miocque S, Polivka M, Goutieres F, et al. Hereditary infantile hemiparesis, retinal arteriolar tortuosity, and leukoencephalopathy. Neurology. 2003;60:57–63.

    Article  PubMed  CAS  Google Scholar 

  172. Bilguvar K, DiLuna ML, Bizzarro MJ, Bayri Y, Schneider KC, Lifton RP, et al. Col4a1 mutation in preterm intraventricular hemorrhage. J Pediatr. 2009;155:743–5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  173. Lanfranconi S, Markus HS. Col4a1 mutations as a monogenic cause of cerebral small vessel disease: a systematic review. Stroke. 2010;41:e513–8.

    Article  PubMed  Google Scholar 

  174. Hamann GF, Okada Y, Fitridge R, del Zoppo GJ. Microvascular basal lamina antigens disappear during cerebral ischemia and reperfusion. Stroke. 1995;26:2120–6.

    Article  PubMed  CAS  Google Scholar 

  175. Zalewska T, Ziemka-Nalecz M, Sarnowska A, Domanska-Janik K. Transient forebrain ischemia modulates signal transduction from extracellular matrix in gerbil hippocampus. Brain Res. 2003;977:62–9.

    Article  PubMed  CAS  Google Scholar 

  176. Horstmann S, Kalb P, Koziol J, Gardner H, Wagner S. Profiles of matrix metalloproteinases, their inhibitors, and laminin in stroke patients: influence of different therapies. Stroke. 2003;34:2165–70.

    Article  PubMed  Google Scholar 

  177. Liesi P, Kaakkola S, Dahl D, Vaheri A. Laminin is induced in astrocytes of adult brain by injury. EMBO J. 1984;3:683–6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  178. Jucker M, Bialobok P, Kleinman HK, Walker LC, Hagg T, Ingram DK. Laminin-like and laminin-binding protein-like immunoreactive astrocytes in rat hippocampus after transient ischemia. Antibody to laminin-binding protein is a sensitive marker of neural injury and degeneration. Ann N Y Acad Sci. 1993;679:245–52.

    Article  PubMed  CAS  Google Scholar 

  179. Ji K, Tsirka SE. Inflammation modulates expression of laminin in the central nervous system following ischemic injury. J Neuroinflammation. 2012;9:159.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  180. Jucker M, Bialobok P, Hagg T, Ingram DK. Laminin immunohistochemistry in brain is dependent on method of tissue fixation. Brain Res. 1992;586:166–70.

    Article  PubMed  CAS  Google Scholar 

  181. Chen ZL, Yao Y, Norris EH, Kruyer A, Jno-Charles O, Akhmerov A, et al. Ablation of astrocytic laminin impairs vascular smooth muscle cell function and leads to hemorrhagic stroke. J Cell Biol. 2013;202:381–95.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  182. Hamann GF, Okada Y, del Zoppo GJ. Hemorrhagic transformation and microvascular integrity during focal cerebral ischemia/reperfusion. J Cereb Blood Flow Metab. 1996;16:1373–8.

    Article  PubMed  CAS  Google Scholar 

  183. Ning M, Sarracino DA, Kho AT, Guo S, Lee SR, Krastins B, et al. Proteomic temporal profile of human brain endothelium after oxidative stress. Stroke. 2011;42:37–43.

    Article  PubMed  CAS  Google Scholar 

  184. Liu J, Gao BB, Feener EP. Proteomic identification of novel plasma kallikrein substrates in the astrocyte secretome. Transl Stroke Res. 2010;1:276–86.

    Article  PubMed  CAS  Google Scholar 

  185. Bix GJ, Gowing EK, Clarkson AN. Perlecan domain v is neuroprotective and affords functional improvement in a photothrombotic stroke model in young and aged mice. Transl Stroke Res. 2013;4:515–23.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  186. Kahle MP, Lee B, Pourmohamad T, Cunningham A, Su H, Kim H, et al. Perlecan domain v is upregulated in human brain arteriovenous malformation and could mediate the vascular endothelial growth factor effect in lesional tissue. Neuroreport. 2012;23:627–30.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  187. Al-Ahmad AJ, Lee B, Saini M, Bix GJ. Perlecan domain v modulates astrogliosis in vitro and after focal cerebral ischemia through multiple receptors and increased nerve growth factor release. Glia. 2011;59:1822–40.

    Article  PubMed  Google Scholar 

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Funding

This work was supported by AHA Scientist Development Grant (16SDG29320001).

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Authors and Affiliations

  1. Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, GA, USA

    Yao Yao

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  1. Yao Yao
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Editors and Affiliations

  1. Department of Vascular Neurosurgery, PLA Rocket Force General Hospital, Beijing, China

    Weijian Jiang

  2. Department of Neurology, University of California Irvine, Irvine, California, USA

    Wengui Yu

  3. Department of Neurosurgery, Tangdu Hospital of Air Force Medical University, Xi’an, China

    Yan Qu

  4. Department of Neurosurgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China

    Zhongsong Shi

  5. Department of Neurology, The First Affiliated Hospital School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China

    Benyan Luo

  6. Department of Anesthesiology, Loma Linda University, Loma Linda, California, USA

    John H. Zhang

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Yao, Y. (2018). Extracellular Matrix in Stroke. In: Jiang, W., Yu, W., Qu, Y., Shi, Z., Luo, B., Zhang, J. (eds) Cerebral Ischemic Reperfusion Injuries (CIRI). Springer Series in Translational Stroke Research. Springer, Cham. https://doi.org/10.1007/978-3-319-90194-7_8

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