{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T23:33:29Z","timestamp":1791848009180,"version":"4.3.4"},"reference-count":117,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,4,11]],"date-time":"2023-04-11T00:00:00Z","timestamp":1681171200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health NINDS","award":["R01 NS197387"],"award-info":[{"award-number":["R01 NS197387"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The extracellular matrix (ECM) surrounds cells in the brain, providing structural and functional support. Emerging studies demonstrate that the ECM plays important roles during development, in the healthy adult brain, and in brain diseases. The aim of this review is to briefly discuss the physiological roles of the ECM and its contribution to the pathogenesis of brain disease, highlighting the gene expression changes, transcriptional factors involved, and a role for microglia in ECM regulation. Much of the research conducted thus far on disease states has focused on \u201comic\u201d approaches that reveal differences in gene expression related to the ECM. Here, we review recent findings on alterations in the expression of ECM-associated genes in seizure, neuropathic pain, cerebellar ataxia, and age-related neurodegenerative disorders. Next, we discuss evidence implicating the transcription factor hypoxia-inducible factor 1 (HIF-1) in regulating the expression of ECM genes. HIF-1 is induced in response to hypoxia, and also targets genes involved in ECM remodeling, suggesting that hypoxia could contribute to ECM remodeling in disease conditions. We conclude by discussing the role microglia play in the regulation of the perineuronal nets (PNNs), a specialized form of ECM in the central nervous system. We show evidence that microglia can modulate PNNs in healthy and diseased brain states. Altogether, these findings suggest that ECM regulation is altered in brain disease, and highlight the role of HIF-1 and microglia in ECM remodeling.<\/jats:p>","DOI":"10.3390\/ijms24087049","type":"journal-article","created":{"date-parts":[[2023,4,12]],"date-time":"2023-04-12T02:57:08Z","timestamp":1681268228000},"page":"7049","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":170,"title":["Extracellular Matrix Regulation in Physiology and in Brain Disease"],"prefix":"10.3390","volume":"24","author":[{"given":"Alyssa","family":"Soles","sequence":"first","affiliation":[{"name":"Department of Neuroscience, University of Minnesota, 321 Church St SE, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0334-2033","authenticated-orcid":false,"given":"Adem","family":"Selimovic","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Minnesota, 321 Church St SE, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaelin","family":"Sbrocco","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Minnesota, 321 Church St SE, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferris","family":"Ghannoum","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Minnesota, 321 Church St SE, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8294-2285","authenticated-orcid":false,"given":"Katherine","family":"Hamel","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Minnesota, 321 Church St SE, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7890-5828","authenticated-orcid":false,"given":"Emmanuel Labrada","family":"Moncada","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Minnesota, 321 Church St SE, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8952-6417","authenticated-orcid":false,"given":"Stephen","family":"Gilliat","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Minnesota, 321 Church St SE, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marija","family":"Cvetanovic","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Minnesota, 321 Church St SE, Minneapolis, MN 55455, USA"},{"name":"Institute for Translational Neuroscience, University of Minnesota, 2101 6th Street SE, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1152\/physrev.00027.2007","article-title":"Diffusion in brain extracellular space","volume":"88","author":"Nicholson","year":"2008","journal-title":"Physiol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1016\/S0166-2236(98)01298-3","article-title":"Perineuronal nets: Past and present","volume":"21","author":"Celio","year":"1998","journal-title":"Trends Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"a005108","DOI":"10.1101\/cshperspect.a005108","article-title":"Extracellular Matrix: Functions in the nervous system","volume":"3","author":"Barros","year":"2011","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"de Jong, J.M., Broekaart, D.W.M., Bongaarts, A., M\u00fchlebner, A., Mills, J.D., van Vliet, E.A., and Aronica, E. (2022). Altered Extracellular Matrix as an Alternative Risk Factor for Epileptogenicity in Brain Tumors. Biomedicines, 10.","DOI":"10.3390\/biomedicines10102475"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Bosiacki, M., G\u0105ssowska-Dobrowolska, M., Kojder, K., Fabia\u0144ska, M., Je\u017cewski, D., Gutowska, I., and Lubkowska, A. (2019). Perineuronal nets and their role in synaptic homeostasis. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20174108"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1002\/dneu.20954","article-title":"Extracellular matrix and matrix receptors in blood-brain barrier formation and stroke","volume":"71","author":"Baeten","year":"2011","journal-title":"Dev. Neurobiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1038\/ncomms2230","article-title":"Fibrinogen-induced perivascular microglial clustering is required for the development of axonal damage in neuroinflammation","volume":"3","author":"Davalos","year":"2012","journal-title":"Nat. Commun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1022754","DOI":"10.3389\/fncel.2022.1022754","article-title":"A glial perspective on the extracellular matrix and perineuronal net remodeling in the central nervous system","volume":"16","author":"Tewari","year":"2022","journal-title":"Front. Cell. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/B978-0-444-63486-3.00007-4","article-title":"Neural ECM in laminar organization and connectivity development in healthy and diseased human brain","volume":"214","author":"Aronica","year":"2014","journal-title":"Prog. Brain Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"180216","DOI":"10.1098\/rsob.180216","article-title":"How the extracellular matrix shapes neural development","volume":"9","author":"Long","year":"2019","journal-title":"Open Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1152\/physrev.2000.80.4.1267","article-title":"Proteoglycans in the developing brain: New conceptual insights for old proteins","volume":"80","author":"Bandtlow","year":"2000","journal-title":"Physiol. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"854956","DOI":"10.3389\/fnsyn.2022.854956","article-title":"The Synaptic Extracellular Matrix: Long-Lived, Stable, and Still Remarkably Dynamic","volume":"14","author":"Dankovich","year":"2022","journal-title":"Front. Synaptic Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1038\/nrn1115","article-title":"Extracellular matrix molecules and synaptic plasticity","volume":"4","author":"Dityatev","year":"2003","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1515\/revneuro-2017-0017","article-title":"Brain extracellular space, hyaluronan, and the prevention of epileptic seizures","volume":"28","author":"Perkins","year":"2017","journal-title":"Rev. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Pint\u00e9r, P., and Alp\u00e1r, A. (2022). The Role of Extracellular Matrix in Human Neurodegenerative Diseases. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231911085"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1111\/j.1750-3639.2008.00195.x","article-title":"Brain extracellular matrix in neurodegeneration","volume":"19","author":"Wiley","year":"2009","journal-title":"Brain Pathol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"707466","DOI":"10.3389\/fnagi.2021.707466","article-title":"Role of the Extracellular Matrix in Alzheimer\u2019s Disease","volume":"13","author":"Sun","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3807","DOI":"10.1111\/ejn.15336","article-title":"Brain extracellular matrix: An upcoming target in neurological and psychiatric disorders","volume":"53","author":"Dityatev","year":"2021","journal-title":"Eur. J. Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3440","DOI":"10.1038\/s41467-020-17328-9","article-title":"Synucleinopathy alters nanoscale organization and diffusion in the brain extracellular space through hyaluronan remodeling","volume":"11","author":"Soria","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1177\/0271678X16655551","article-title":"Matrix metalloproteinases in the brain and blood-brain barrier: Versatile breakers and makers","volume":"36","author":"Rempe","year":"2016","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.pmbts.2017.02.005","article-title":"Biochemical and Biological Attributes of Matrix Metalloproteinases","volume":"147","author":"Cui","year":"2017","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1189\/jlb.0306152","article-title":"Matrix metalloproteinases, their production by monocytes and macrophages and their potential role in HIV-related diseases","volume":"80","author":"Webster","year":"2006","journal-title":"J. Leukoc. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1177\/15357597211018688","article-title":"Perineuronal Net Dynamics in the Pathophysiology of Epilepsy","volume":"21","author":"Chaunsali","year":"2021","journal-title":"Epilepsy Curr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1002\/dneu.20974","article-title":"Extracellular matrix and perineuronal nets in CNS repair","volume":"71","author":"Kwok","year":"2011","journal-title":"Dev. Neurobiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1016\/j.neuint.2012.08.007","article-title":"The perineuronal net component of the extracellular matrix in plasticity and epilepsy","volume":"61","author":"McRae","year":"2012","journal-title":"Neurochem. Int."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2423","DOI":"10.1177\/0271678X211004307","article-title":"Global proteomic analysis of extracellular matrix in mouse and human brain highlights relevance to cerebrovascular disease","volume":"41","author":"Pokhilko","year":"2021","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"dev175596","DOI":"10.1242\/dev.175596","article-title":"The extracellular matrix in development","volume":"147","author":"Walma","year":"2020","journal-title":"Development"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13036-022-00292-x","article-title":"Extracellular matrix dynamics: Tracking in biological systems and their implications","volume":"16","author":"Hu","year":"2022","journal-title":"J. Biol. Eng."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1038\/nrn2898","article-title":"The dual role of the extracellular matrix in synaptic plasticity and homeostasis","volume":"11","author":"Dityatev","year":"2010","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6850","DOI":"10.1111\/febs.15776","article-title":"A guide to the composition and functions of the extracellular matrix","volume":"288","author":"Karamanos","year":"2021","journal-title":"FEBS J."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Fudge, N.J., and Mearow, K.M. (2013). Extracellular matrix-associated gene expression in adult sensory neuron populations cultured on a laminin substrate. BMC Neurosci., 14.","DOI":"10.1186\/1471-2202-14-15"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/S0959-437X(05)80183-2","article-title":"Extracellular matrix and neurite outgrowth","volume":"2","author":"Letourneau","year":"1992","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"109827","DOI":"10.1016\/j.cellsig.2020.109827","article-title":"Metalloprotease ADAMTS-1 decreases cell migration and invasion modulating the spatiotemporal dynamics of Cdc42 activity","volume":"77","author":"Hodgson","year":"2021","journal-title":"Cell. Signal."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.neuroscience.2018.10.021","article-title":"Gene Expression Profiling of Two Epilepsy Models Reveals the ECM\/Integrin signaling Pathway is Involved in Epiletogenesis","volume":"396","author":"Han","year":"2019","journal-title":"Neuroscience"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.matbio.2015.01.014","article-title":"ADAMTS expression and function in central nervous system injury and disorders","volume":"44\u201346","author":"Gottschall","year":"2015","journal-title":"Matrix Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1016\/j.ajpath.2016.12.001","article-title":"Cathepsin H\u2013Mediated Degradation of HDAC4 for Matrix Metalloproteinase Expression in Hepatic Stellate Cells: Implications of Epigenetic Suppression of Matrix Metalloproteinases in Fibrosis through Stabilization of Class IIa Histone Deacetylases","volume":"187","author":"Yang","year":"2017","journal-title":"Am. J. Pathol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1038\/nn.4394","article-title":"Mechanosensing is critical for axon growth in the developing brain","volume":"19","author":"Koser","year":"2016","journal-title":"Nat. Neurosci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1111\/j.1528-1157.1996.tb00541.x","article-title":"The pilocarpine model of epilepsy in mice","volume":"37","author":"Cavalheiro","year":"1996","journal-title":"Epilepsia"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2887","DOI":"10.1016\/j.neubiorev.2013.10.011","article-title":"The kainic acid models of temporal lobe epilepsy","volume":"37","author":"Levesque","year":"2013","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1093\/hmg\/ddy139","article-title":"Neurodegenerative diseases have genetic hallmarks of autoinflammatory disease","volume":"27","author":"Richards","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1016\/S0092-8674(00)80483-3","article-title":"Neuronal death in the hippocampus is promoted by plasmin-catalyzed degradation of laminin","volume":"91","author":"Chen","year":"1997","journal-title":"Cell"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.eplepsyres.2017.02.021","article-title":"Increased metalloproteinase activity in the hippocampus following status epilepticus","volume":"132","author":"Dubeya","year":"2017","journal-title":"Eplilepsy Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/0014-5793(95)01539-6","article-title":"Degradation of cartilage aggrecan by collagenase-3 (MMP-13)","volume":"380","author":"Fosang","year":"1996","journal-title":"FEBS Lett."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.brainres.2005.07.036","article-title":"Focal cerebral ischemia induces changes in both MMP-13 and aggrecan around individual neurons","volume":"1056","author":"Nagel","year":"2005","journal-title":"Brain Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1083\/jcb.200708213","article-title":"Important role of matrix metalloproteinase 9 in epileptogenesis","volume":"180","author":"Wilczynski","year":"2008","journal-title":"J. Cell Biol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Sita\u0161, B., Bobi\u0107-Rasonja, M., Mrak, G., Trnski, S., Krbot Skori\u0107, M., Ore\u0161kovi\u0107, D., Knezovi\u0107, V., Gad\u017ee, \u017d.P., Petanjek, Z., and \u0160imi\u0107, G. (2022). Reorganization of the Brain Extracellular Matrix in Hippocampal Sclerosis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23158197"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1097\/j.pain.0000000000001471","article-title":"Genetic pathway analysis reveals a major role for extracellular matrix organization in inflammatory and neuropathic pain","volume":"160","author":"Parisien","year":"2019","journal-title":"Pain"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BSR20212411","article-title":"Extracellular matrix and synapse formation","volume":"43","author":"Yang","year":"2023","journal-title":"Biosci. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.matbio.2018.02.023","article-title":"Cartilage oligomeric matrix protein: COMPopathies and beyond","volume":"71\u201372","author":"Posey","year":"2018","journal-title":"Matrix Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1038\/ng0894-513","article-title":"Identification and characterization of the gene causing type 1 spinocerebellar ataxia","volume":"7","author":"Banfi","year":"1994","journal-title":"Nat. Genet."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1007\/s12311-008-0009-0","article-title":"Clinical, genetic, molecular, and pathophysiological insights into spinocerebellar ataxia type 1","volume":"7","author":"Goold","year":"2008","journal-title":"Cerebellum"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1093\/hmg\/ddz265","article-title":"Cerebellar contribution to the cognitive alterations in SCA1: Evidence from mouse models","volume":"29","author":"Asher","year":"2020","journal-title":"Hum. Mol. Genet."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1038\/nrn.2017.92","article-title":"Polyglutamine spinocerebellar ataxias-from genes to potential treatments","volume":"18","author":"Paulson","year":"2017","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1007\/s12311-021-01311-1","article-title":"Consensus Paper: Strengths and Weaknesses of Animal Models of Spinocerebellar Ataxias and Their Clinical Implications. Cerebellum","volume":"21","author":"Cendelin","year":"2021","journal-title":"Cerebellum"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/S0896-6273(02)00733-X","article-title":"A long CAG repeat in the mouse Sca1 locus replicates SCA1 features and reveals the impact of protein solubility on selective neurodegeneration","volume":"34","author":"Watase","year":"2002","journal-title":"Neuron"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1016\/j.devcel.2011.08.017","article-title":"Atxn1 protein family and Cic regulate extracellular matrix remodeling and lung alveolarizatio","volume":"21","author":"Lee","year":"2011","journal-title":"Dev Cell."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Hamel, K., Sheeler, C., Rosa, J.-G., Gilliat, S., Zhang, Y., and Cvetanovic, M. (2022). Increased vulnerability of Purkinje cells in the posterior cerebellum of SCA1 mice is associated with molecular and cellular alterations related to disease pathology. bioRxiv.","DOI":"10.1101\/2022.02.24.481789"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1126\/science.1185152","article-title":"Cbln1 Is a Ligand for an Orphan Glutamate Receptor d2, a Bidirectional Synapse Organizer","volume":"328","author":"Matsuda","year":"2010","journal-title":"Science"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1016\/j.cell.2010.04.035","article-title":"Trans-synaptic interaction of GluR\u03b42 and neurexin through Cbln1 mediates synapse formation in the cerebellum","volume":"141","author":"Uemura","year":"2010","journal-title":"Cell"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"eabb4853","DOI":"10.1126\/science.abb4853","article-title":"A synthetic synaptic organizer protein restores glutamatergic neuronal circuits","volume":"369","author":"Suzuki","year":"2020","journal-title":"Science"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"12778","DOI":"10.1523\/JNEUROSCI.2579-11.2011","article-title":"Abnormalities in the Climbing Fiber-Purkinje Cell Circuitry Contribute to Neuronal Dysfunction in ATXN1[82Q] Mice","volume":"31","author":"Barnes","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.biochi.2004.10.006","article-title":"Matrikines in the regulation of extracellular matrix degradation","volume":"87","author":"Maquart","year":"2005","journal-title":"Biochimie"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1828","DOI":"10.1172\/JCI115204","article-title":"Marked longevity of human lung parenchymal elastic fibers deduced from prevalence of D-aspartate and nuclear weapons-related radiocarbon","volume":"87","author":"Shapiro","year":"1991","journal-title":"J. Clin. Investig."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1038\/jid.1982.28","article-title":"Elastases and elastin degradation","volume":"79","author":"Werb","year":"1982","journal-title":"J. Investig. Dermatol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.critrevonc.2003.06.007","article-title":"An introduction to matrikines: Extracellular matrix-derived peptides which regulate cell activity-Implication in tumor invasion","volume":"49","author":"Maquart","year":"2004","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2473","DOI":"10.1007\/s10571-021-01140-0","article-title":"Elastin-Derived Peptides in the Central Nervous System: Friend or Foe","volume":"42","author":"Szychowski","year":"2022","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1093\/cvr\/cvw061","article-title":"Matrix ageing and vascular impacts: Focus on elastin fragmentation","volume":"110","author":"Duca","year":"2016","journal-title":"Cardiovasc. Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"18703","DOI":"10.1002\/anie.201912399","article-title":"Significant Upregulation of Alzheimer\u2019s \u03b2-Amyloid Levels in a Living System Induced by Extracellular Elastin Polypeptides","volume":"58","author":"Ma","year":"2019","journal-title":"Angew. Chemie-Int. Ed."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Lajoie, A.C., Lafontaine, A.L., Kimoff, R.J., and Kaminska, M. (2020). Obstructive sleep apnea in neurodegenerative disorders: Current evidence in support of benefit from sleep apnea treatment. J. Clin. Med., 9.","DOI":"10.3390\/jcm9020297"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"222","DOI":"10.5935\/1984-0063.20190081","article-title":"Increase in the frequency of obstructive sleep apnea in elderly people","volume":"12","author":"Ernst","year":"2019","journal-title":"Sleep Sci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.sleep.2003.07.002","article-title":"Sleep disorders in multiple system atrophy: A correlative video-polysomnographic study","volume":"5","author":"Vetrugno","year":"2004","journal-title":"Sleep Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"zsaa191","DOI":"10.1093\/sleep\/zsaa191","article-title":"Stridor during sleep: Description of 81 consecutive cases diagnosed in a tertiary sleep disorders center","volume":"44","author":"Silva","year":"2021","journal-title":"Sleep"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"zsy015","DOI":"10.1093\/sleep\/zsy015","article-title":"Sleep-disordered breathing in epilepsy: Epidemiology, mechanisms, and treatment","volume":"41","author":"Sivathamboo","year":"2018","journal-title":"Sleep"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11910-019-0968-1","article-title":"Sleep Disorders in Hereditary Ataxias","volume":"19","author":"Huebra","year":"2019","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_75","first-page":"186","article-title":"The Cognitive Effects of Obstructive Sleep Apnea: An Updated Meta-analysis","volume":"31","author":"Stranks","year":"2015","journal-title":"Arch. Clin. Neuropsychol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s11910-011-0248-1","article-title":"Sleep-disordered breathing in neurodegenerative diseases","volume":"12","author":"Gaig","year":"2012","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Punjabi, N.M., Caffo, B.S., Goodwin, J.L., Gottlieb, D.J., Newman, A.B., O\u2019Connor, G.T., Rapoport, D.M., Redline, S., Resnick, H.E., and Robbins, J.A. (2009). Sleep-disordered breathing and mortality: A prospective cohort study. PLoS Med., 6.","DOI":"10.1371\/journal.pmed.1000132"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s00441-009-0841-7","article-title":"Extracellular matrix genes as hypoxia-inducible targets","volume":"339","author":"Myllyharju","year":"2010","journal-title":"Cell Tissue Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/s41392-023-01332-8","article-title":"Hypoxic microenvironment in cancer: Molecular mechanisms and therapeutic interventions","volume":"8","author":"Chen","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"99","DOI":"10.3389\/fcell.2022.810980","article-title":"The Signature of Moderate Perinatal Hypoxia on Cortical Organization and Behavior: Altered PNN-Parvalbumin Interneuron Connectivity of the Cingulate Circuitries","volume":"10","author":"Trnski","year":"2022","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"703084","DOI":"10.3389\/fcell.2021.703084","article-title":"Hypoxia-Inducible Factor (HIF) in Ischemic Stroke and Neurodegenerative Disease","volume":"9","author":"Mitroshina","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1988","DOI":"10.1523\/JNEUROSCI.5323-07.2008","article-title":"The good, the bad, and the cell type-specific roles of hypoxia inducible factor-1\u03b1 in neurons and astrocytes","volume":"28","author":"Vangeison","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s12987-021-00302-y","article-title":"Pericyte, but not astrocyte, hypoxia inducible factor-1 (HIF-1) drives hypoxia-induced vascular permeability in vivo","volume":"19","author":"Baumann","year":"2022","journal-title":"Fluids Barriers CNS"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1016\/j.neuron.2015.09.050","article-title":"Activating injury-responsive genes with hypoxia enhances axon regeneration through neuronal HIF-1\u03b1","volume":"88","author":"Cho","year":"2015","journal-title":"Neuron"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Allen, S.P., Seehra, R.S., Heath, P.R., Hall, B.P.C., Bates, J., Garwood, C.J., Matuszyk, M.M., Wharton, S.B., and Simpson, J.E. (2020). Transcriptomic analysis of human astrocytes in vitro reveals hypoxia-induced mitochondrial dysfunction, modulation of metabolism, and dysregulation of the immune response. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21218028"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1002\/jcp.21746","article-title":"Hypoxia-induced matrix metalloproteinase-13 expression in astrocytes enhances permeability of brain endothelial cells","volume":"220","author":"Lu","year":"2009","journal-title":"J. Cell. Physiol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1046\/j.1471-4159.1995.64041513.x","article-title":"Cytokines Regulate Gelatinase A and B (Matrix Metalloproteinase 2 and 9) Activity in Cultured Rat Astrocytes","volume":"64","author":"Gottschall","year":"1995","journal-title":"J. Neurochem."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.jneuroim.2006.01.014","article-title":"Evidence that hypoxia-inducible factor-1 (HIF-1) mediates transcriptional activation of interleukin-1\u03b2 (IL-1\u03b2) in astrocyte cultures","volume":"174","author":"Zhang","year":"2006","journal-title":"J. Neuroimmunol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1038\/s41593-018-0242-x","article-title":"Microglia in neurodegeneration","volume":"21","author":"Hickman","year":"2018","journal-title":"Nat. Neurosci."},{"key":"ref_90","first-page":"914104","article-title":"The role of microglia and matrix metalloproteinases involvement in neuroinflammation and gliomas","volume":"2013","author":"Bechmann","year":"2013","journal-title":"Clin. Dev. Immunol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"282","DOI":"10.3389\/fnagi.2017.00282","article-title":"Acute hypoxia induced an imbalanced M1\/M2 activation of microglia through NF-\u03baB signaling in Alzheimer\u2019s disease mice and wild-type littermates. Front","volume":"9","author":"Zhang","year":"2017","journal-title":"Aging Neurosci."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/1742-2094-4-12","article-title":"Hypoxia-inducible factor-1 (HIF-1) is involved in the regulation of hypoxia-stimulated expression of monocyte chemoattractant protein-1 (MCP-1\/CCL2) and MCP-5 (Ccl12) in astrocytes","volume":"4","author":"Callaghan","year":"2007","journal-title":"J. Neuroinflamm."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Smith, S.M.C., Friedle, S.A., and Watters, J.J. (2013). Chronic intermittent hypoxia exerts CNS region-specific effects on rat microglial inflammatory and TLR4 gene expression. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0081584"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.cbi.2014.05.001","article-title":"Regulatory crosstalk and interference between the xenobiotic and hypoxia sensing pathways at the AhR-ARNT-HIF1\u03b1 signaling node","volume":"218","author":"Vorrink","year":"2014","journal-title":"Chem. Biol. Interact."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"110445","DOI":"10.1016\/j.cellsig.2022.110445","article-title":"Mutual antagonism between aryl hydrocarbon receptor and hypoxia-inducible factor-1\u03b1 (AhR\/HIF-1\u03b1) signaling: Impact on the aging process","volume":"99","author":"Salminen","year":"2022","journal-title":"Cell. Signal."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1515\/BC.2006.144","article-title":"The impact of aryl hydrocarbon receptor signaling on matrix metabolism: Implications for development and disease","volume":"387","author":"Hillegass","year":"2006","journal-title":"Biol. Chem."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Grishanova, A.Y., and Perepechaeva, M.L. (2022). Aryl Hydrocarbon Receptor in Oxidative Stress as a Double Agent and Its Biological and Therapeutic Significance. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23126719"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Ojo, E.S., and Tischkau, S.A. (2021). The role of ahr in the hallmarks of brain aging: Friend and foe. Cells, 10.","DOI":"10.3390\/cells10102729"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"5309328","DOI":"10.1155\/2016\/5309328","article-title":"Aryl Hydrocarbon Receptor Activation by TCDD Modulates Expression of Extracellular Matrix Remodeling Genes during Experimental Liver Fibrosis","volume":"2016","author":"Lamb","year":"2016","journal-title":"Biomed. Res. Int."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"8477","DOI":"10.1038\/s41598-020-65414-1","article-title":"The aryl hydrocarbon receptor pathway controls matrix metalloproteinase-1 and collagen levels in human orbital fibroblasts","volume":"10","author":"Roztocil","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.expneurol.2007.01.036","article-title":"Matrix metalloproteinase-9 regulates TNF-\u03b1 and FasL expression in neuronal, glial cells and its absence extends life in a transgenic mouse model of amyotrophic lateral sclerosis","volume":"205","author":"Kiaei","year":"2007","journal-title":"Exp. Neurol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.neuron.2013.12.009","article-title":"Neuronal matrix Metalloproteinase-9 is a determinant of selective Neurodegeneration","volume":"81","author":"Kaplan","year":"2014","journal-title":"Neuron"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"215","DOI":"10.2119\/molmed.2014.00032","article-title":"Hypoxia-inducible aryl hydrocarbon receptor nuclear translocator (ARNT) (HIF-1\u03b2): Is it a rare exception?","volume":"20","author":"Mandl","year":"2014","journal-title":"Mol. Med."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"102700","DOI":"10.1016\/j.conb.2023.102700","article-title":"The brain\u2019s polymath: Emerging roles of microglia throughout brain development","volume":"79","author":"Wong","year":"2023","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2472","DOI":"10.1038\/s41423-021-00751-3","article-title":"Microglia as hackers of the matrix: Sculpting synapses and the extracellular space","volume":"18","author":"Crapser","year":"2021","journal-title":"Cell. Mol. Immunol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.tins.2019.04.003","article-title":"Perineuronal Nets: Plasticity, Protection, and Therapeutic Potential","volume":"42","author":"Reichelt","year":"2019","journal-title":"Trends Neurosci."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1126\/science.abl6773","article-title":"Microglia-mediated degradation of perineuronal nets promotes pain","volume":"377","author":"Tansley","year":"2022","journal-title":"Science"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.cell.2020.05.050","article-title":"Microglial Remodeling of the Extracellular Matrix Promotes Synapse Plasticity","volume":"182","author":"Nguyen","year":"2020","journal-title":"Cell"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Strackeljan, L., Baczynska, E., Cangalaya, C., Baidoe-Ansah, D., Wlodarczyk, J., Kaushik, R., and Dityatev, A. (2021). Microglia depletion-induced remodeling of extracellular matrix and excitatory synapses in the hippocampus of adult mice. Cells, 10.","DOI":"10.3390\/cells10081862"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"102919","DOI":"10.1016\/j.ebiom.2020.102919","article-title":"Microglia facilitate loss of perineuronal nets in the Alzheimer\u2019s disease brain","volume":"58","author":"Crapser","year":"2020","journal-title":"EBioMedicine"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1093\/brain\/awz363","article-title":"Microglial depletion prevents extracellular matrix changes and striatal volume reduction in a model of Huntington\u2019s disease","volume":"143","author":"Crapser","year":"2020","journal-title":"Brain"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"eabg1601","DOI":"10.1126\/sciadv.abg1601","article-title":"Microglial dyshomeostasis drives perineuronal net and synaptic loss in a CSF1R+\/\u2212 mouse model of ALSP, which can be rescued via CSF1R inhibitors","volume":"7","author":"Arreola","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Sheeler, C., Rosa, J., Ferro, A., Mcadams, B., Borgenheimer, E., and Cvetanovic, M. (2020). Glia in Neurodegeneration: The Housekeeper, the Defender and the Perpetrator. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21239188"},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Plaza-Zabala, A., Sierra-Torre, V., and Sierra, A. (2017). Autophagy and microglia: Novel partners in neurodegeneration and aging. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18030598"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"637549","DOI":"10.3389\/fnsyn.2021.637549","article-title":"Poly I:C Activated Microglia Disrupt Perineuronal Nets and Modulate Synaptic Balance in Primary Hippocampal Neurons in vitro","volume":"13","author":"Wegrzyn","year":"2021","journal-title":"Front. Synaptic Neurosci."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"851988","DOI":"10.3389\/fnint.2022.851988","article-title":"Update on Perineuronal Net Staining With Wisteria floribunda Agglutinin (WFA)","volume":"16","author":"Meinicke","year":"2022","journal-title":"Front. Integr. Neurosci."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"5779","DOI":"10.1523\/JNEUROSCI.0434-21.2021","article-title":"Regulation of perineuronal nets in the adult cortex by the activity of the cortical network","volume":"41","author":"Devienne","year":"2021","journal-title":"J. Neurosci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/8\/7049\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:13:45Z","timestamp":1760123625000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/8\/7049"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,11]]},"references-count":117,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["ijms24087049"],"URL":"https:\/\/doi.org\/10.3390\/ijms24087049","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,11]]}}}