{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:09:29Z","timestamp":1792804169593,"version":"4.5.0"},"reference-count":78,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,5,24]],"date-time":"2023-05-24T00:00:00Z","timestamp":1684886400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Centre","award":["2019\/35\/N\/NZ7\/04180"],"award-info":[{"award-number":["2019\/35\/N\/NZ7\/04180"]}],"id":[{"id":"https:\/\/ror.org\/03ha2q922","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Science Centre","award":["POWR.03.02.00-00-I013\/16"],"award-info":[{"award-number":["POWR.03.02.00-00-I013\/16"]}],"id":[{"id":"https:\/\/ror.org\/03ha2q922","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Maj Institute of Pharmacology Polish Academy of Sciences","award":["2019\/35\/N\/NZ7\/04180"],"award-info":[{"award-number":["2019\/35\/N\/NZ7\/04180"]}],"id":[{"id":"https:\/\/ror.org\/01dr6c206","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Maj Institute of Pharmacology Polish Academy of Sciences","award":["POWR.03.02.00-00-I013\/16"],"award-info":[{"award-number":["POWR.03.02.00-00-I013\/16"]}],"id":[{"id":"https:\/\/ror.org\/01dr6c206","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Ischaemic stroke is characterized by a sudden loss of blood circulation to an area of the brain, resulting in a corresponding loss of neurologic function. As a result of this process, neurons in the ischaemic core are deprived of oxygen and trophic substances and are consequently destroyed. Tissue damage in brain ischaemia results from a complex pathophysiological cascade comprising various distinct pathological events. Ischaemia leads to brain damage by stimulating many processes, such as excitotoxicity, oxidative stress, inflammation, acidotoxicity, and apoptosis. Nevertheless, less attention has been given to biophysical factors, including the organization of the cytoskeleton and the mechanical properties of cells. Therefore, in the present study, we sought to evaluate whether the oxygen-glucose deprivation (OGD) procedure, which is a commonly accepted experimental model of ischaemia, could affect cytoskeleton organization and the paracrine immune response. The abovementioned aspects were examined ex vivo in organotypic hippocampal cultures (OHCs) subjected to the OGD procedure. We measured cell death\/viability, nitric oxide (NO) release, and hypoxia-inducible factor 1\u03b1 (HIF-1\u03b1) levels. Next, the impact of the OGD procedure on cytoskeletal organization was evaluated using combined confocal fluorescence microscopy (CFM) and atomic force microscopy (AFM). Concurrently, to find whether there is a correlation between biophysical properties and the immune response, we examined the impact of OGD on the levels of crucial ischaemia cytokines (IL-1\u03b2, IL-6, IL-18, TNF-\u03b1, IL-10, IL-4) and chemokines (CCL3, CCL5, CXCL10) in OHCs and calculated Pearsons\u2019 and Spearman\u2019s rank correlation coefficients. The results of the current study demonstrated that the OGD procedure intensified cell death and nitric oxide release and led to the potentiation of HIF-1\u03b1 release in OHCs. Moreover, we presented significant disturbances in the organization of the cytoskeleton (actin fibers, microtubular network) and cytoskeleton-associated protein 2 (MAP-2), which is a neuronal marker. Simultaneously, our study provided new evidence that the OGD procedure leads to the stiffening of OHCs and a malfunction in immune homeostasis. A negative linear correlation between tissue stiffness and branched IBA1 positive cells after the OGD procedure suggests the pro-inflammatory polarization of microglia. Moreover, the negative correlation of pro- and positive anti-inflammatory factors with actin fibers density indicates an opposing effect of the immune mediators on the rearrangement of cytoskeleton induced by OGD procedure in OHCs. Our study constitutes a basis for further research and provides a rationale for integrating biomechanical and biochemical methods in studying the pathomechanism of stroke-related brain damage. Furthermore, presented data pointed out the interesting direction of proof-of-concept studies, in which follow-up may establish new targets for brain ischemia therapy.<\/jats:p>","DOI":"10.3390\/cells12111465","type":"journal-article","created":{"date-parts":[[2023,5,25]],"date-time":"2023-05-25T01:36:28Z","timestamp":1684978588000},"page":"1465","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Oxygen-Glucose Deprivation in Organotypic Hippocampal Cultures Leads to Cytoskeleton Rearrangement and Immune Activation: Link to the Potential Pathomechanism of Ischaemic Stroke"],"prefix":"10.3390","volume":"12","author":[{"given":"Natalia","family":"Bryniarska-Kubiak","sequence":"first","affiliation":[{"name":"Laboratory of Immunoendocrinology, Department of Experimental Neuroendocrinology, Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Sm\u0119tna St., 31-343 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3959-397X","authenticated-orcid":false,"given":"Andrzej","family":"Kubiak","sequence":"additional","affiliation":[{"name":"Department of Biophysical Microstructures, Institute of Nuclear Physics, Polish Academy of Sciences, 152 Radzikowskiego St., 31-342 Krak\u00f3w, Poland"},{"name":"Laboratory of Stem Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 7 Gronostajowa St., 30-387 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9573-7026","authenticated-orcid":false,"given":"Ewa","family":"Trojan","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoendocrinology, Department of Experimental Neuroendocrinology, Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Sm\u0119tna St., 31-343 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9646-216X","authenticated-orcid":false,"given":"Julita","family":"Weso\u0142owska","sequence":"additional","affiliation":[{"name":"Laboratory for In Vivo and In Vitro Imaging, Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Sm\u0119tna St., 31-343 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0844-8662","authenticated-orcid":false,"given":"Ma\u0142gorzata","family":"Lekka","sequence":"additional","affiliation":[{"name":"Department of Biophysical Microstructures, Institute of Nuclear Physics, Polish Academy of Sciences, 152 Radzikowskiego St., 31-342 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3109-0040","authenticated-orcid":false,"given":"Agnieszka","family":"Basta-Kaim","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoendocrinology, Department of Experimental Neuroendocrinology, Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Sm\u0119tna St., 31-343 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/S0074-7696(02)21011-6","article-title":"Molecular mechanisms of cerebral ischemia-induced neuronal death","volume":"221","author":"Hou","year":"2002","journal-title":"Int. Rev. Cytol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1002\/med.21817","article-title":"Mechanisms of neuronal cell death in ischemic stroke and their therapeutic implications","volume":"42","author":"Tuo","year":"2021","journal-title":"Med. Res. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1038\/s41578-019-0169-1","article-title":"The stiffness of living tissues and its implications for tissue engineering","volume":"5","author":"Gasperini","year":"2020","journal-title":"Nat. Rev. Mater."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1038\/s41567-018-0092-1","article-title":"Mitotic cells generate protrusive extracellular forces to divide in three-dimensional microenvironments","volume":"14","author":"Nam","year":"2018","journal-title":"Nat. Phys."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1038\/nrm.2017.108","article-title":"Mechanical forces direct stem cell behaviour in development and regeneration","volume":"18","author":"Vining","year":"2017","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/15476278.2015.1019687","article-title":"Tissue stiffness dictates development, homeostasis, and disease progression","volume":"11","author":"Handorf","year":"2015","journal-title":"Organogenesis"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1038\/nnano.2012.196","article-title":"Atomic force microscopy: A tip for diagnosing cancer","volume":"7","author":"Lekka","year":"2012","journal-title":"Nat. Nanotechnol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1038\/nrc3080","article-title":"The physics of cancer: The role of physical interactions and mechanical forces in metastasis","volume":"11","author":"Wirtz","year":"2011","journal-title":"Nat. Rev. Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/bs.ctm.2020.08.002","article-title":"Cell membrane mechanics and mechanosensory transduction","volume":"86","author":"Martinac","year":"2020","journal-title":"Curr. Top. Membr."},{"key":"ref_10","first-page":"245","article-title":"Roles of the cytoskeleton, cell adhesion and rho signalling in mechanosensing and mechanotransduction","volume":"161","author":"Ohashi","year":"2017","journal-title":"J. Biochem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"6626","DOI":"10.1073\/pnas.0711704105","article-title":"Rapid signal transduction in living cells is a unique feature of mechanotransduction","volume":"105","author":"Na","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1007\/s12551-019-00587-2","article-title":"Mechanotransduction in neuronal cell development and functioning","volume":"11","author":"Chighizola","year":"2019","journal-title":"Biophys. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1038\/s41551-018-0334-7","article-title":"Solid stress in brain tumours causes neuronal loss and neurological dysfunction and can be reversed by lithium","volume":"3","author":"Seano","year":"2019","journal-title":"Nat. Biomed. Eng."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"485","DOI":"10.7863\/jum.2013.32.3.485","article-title":"Evidence of changes in brain tissue stiffness after ischemic stroke derived from ultrasound-based elastography","volume":"32","author":"Xu","year":"2013","journal-title":"J. Ultrasound Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/0165-0270(91)90128-M","article-title":"A simple method for organotypic cultures of nervous tissue","volume":"37","author":"Stoppini","year":"1991","journal-title":"J. Neurosci. Methods"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.pharep.2019.02.017","article-title":"Protective effects of polydatin in free and nanocapsulated form on changes caused by lipopolysaccharide in hippocampal organotypic cultures","volume":"71","author":"Szczepanowicz","year":"2019","journal-title":"Pharmacol. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"21","DOI":"10.5214\/ans.0972.7531.1118107","article-title":"The neuroprotective effect of bone marrow stem cells is not dependent on direct cell contact with hypoxic injured tissue: Experimental Neurology 2009; 215: 317\u2013327","volume":"18","author":"Sarnowska","year":"2011","journal-title":"Ann. Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1111\/j.1530-0277.2008.00649.x","article-title":"Age and gender differences in response to neonatal ethanol withdrawal and polyamine challenge in organotypic hippocampal cultures","volume":"32","author":"Barron","year":"2008","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1111\/j.1460-9568.2008.06172.x","article-title":"Interaction between neuropeptide Y (NPY) and brain-derived neurotrophic factor in NPY-mediated neuroprotection against excitotoxicity: A role for microglia","volume":"27","author":"Xapelli","year":"2008","journal-title":"Eur. J. Neurosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.bcp.2016.05.008","article-title":"Beneficial impact of intracerebroventricular fractalkine administration on behavioral and biochemical changes induced by prenatal stress in adult rats: Possible role of NLRP3 inflammasome pathway","volume":"113","author":"Trojan","year":"2016","journal-title":"Biochem. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Tylek, K., Trojan, E., Le\u015bkiewicz, M., Regulska, M., Bryniarska, N., Curzytek, K., Lacivita, E., Leopoldo, M., and Basta-Kaim, A. (2021). Time-Dependent Protective and Pro-Resolving Effects of FPR2 Agonists on Lipopolysaccharide-Exposed Microglia Cells Involve Inhibition of NF-\u03baB and MAPKs Pathways. Cells, 10.","DOI":"10.3390\/cells10092373"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2452","DOI":"10.1038\/nprot.2006.180","article-title":"Staining protocol for organotypic hippocampal slice cultures","volume":"1","author":"Gogolla","year":"2006","journal-title":"Nat. Protoc."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1088\/0957-4484\/6\/1\/001","article-title":"Calculation of thermal noise in atomic force microscopy","volume":"6","author":"Butt","year":"1995","journal-title":"Nanotechnology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1002\/cm.21217","article-title":"Glutaraldehyde fixation preserves the trend of elasticity alterations for endothelial cells exposed to TNF-\u03b1","volume":"72","author":"Danilkiewicz","year":"2015","journal-title":"Cytoskeleton"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/0020-7225(65)90019-4","article-title":"The relation between load and penetration in the axisymmetric boussinesq problem for a punch of arbitrary profile","volume":"3","author":"Sneddon","year":"1965","journal-title":"Int. J. Eng. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.molcel.2010.09.022","article-title":"Hypoxia-inducible factors and the response to hypoxic stress","volume":"40","author":"Majmundar","year":"2010","journal-title":"Mol. Cell"},{"key":"ref_27","first-page":"491","article-title":"Impact of developmental origin, niche mechanics and oxygen availability on osteogenic differentiation capacity of mesenchymal stem\/stromal cells","volume":"66","author":"Bryniarska","year":"2019","journal-title":"Acta Biochim. Pol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Nosi, D., Lana, D., Giovannini, M.G., Delfino, G., and Zecchi-Orlandini, S. (2021). Neuroinflammation: Integrated Nervous Tissue Response through Intercellular Interactions at the \u201cWhole System\u201d Scale. Cells, 10.","DOI":"10.3390\/cells10051195"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-G\u00f3mez, J.A., Kavanagh, E., Engskog-Vlachos, P., Engskog, M.K., Herrera, A.J., Espinosa-Oliva, A.M., Joseph, B., Hajji, N., Venero, J.L., and Burguillos, M.A. (2020). Microglia: Agents of the CNS Pro-Inflammatory Response. Cells, 9.","DOI":"10.3390\/cells9071717"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4226","DOI":"10.1007\/s12035-015-9362-4","article-title":"Organotypic Hippocampal Slices as Models for Stroke and Traumatic Brain Injury","volume":"53","author":"Li","year":"2015","journal-title":"Mol. Neurobiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1038\/nprot.2006.228","article-title":"Preparation of organotypic hippocampal slice cultures: Interface method","volume":"1","author":"Yu","year":"2006","journal-title":"Nat. Protoc."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/1742-2094-7-43","article-title":"Central administration of lipopolysaccharide induces depressive-like behavior in vivo and activates brain indoleamine 2,3 dioxygenase in murine organotypic hippocampal slice cultures","volume":"7","author":"Fu","year":"2010","journal-title":"J. Neuroinflamm."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"205","DOI":"10.30773\/pi.2017.04.02","article-title":"Long-Term Culture of Organotypic Hippocampal Slice from Old 3xTg-AD Mouse: An ex vivo Model of Alzheimer\u2019s Disease","volume":"15","author":"Jang","year":"2018","journal-title":"Psychiatry Investig."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.neuroscience.2013.10.021","article-title":"Modeling nigrostriatal degeneration in organotypic cultures, a new ex vivo model of Parkinson\u2019s disease","volume":"256","author":"Daviaud","year":"2013","journal-title":"Neuroscience"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2124","DOI":"10.1161\/01.STR.27.11.2124","article-title":"Selective N-type calcium channel antagonist omega conotoxin MVIIA is neuroprotective against hypoxic neurodegeneration in organotypic hippocampal-slice cultures","volume":"27","author":"Pringle","year":"1996","journal-title":"Stroke"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.brainresbull.2017.10.010","article-title":"A novel method for oxygen glucose deprivation model in organotypic spinal cord slices","volume":"135","author":"Liu","year":"2017","journal-title":"Brain Res. Bull."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Figiel-Dabrowska, A., Radoszkiewicz, K., Rybkowska, P., Krzesniak, N.E., Sulejczak, D., and Sarnowska, A. (2021). Neurogenic and Neuroprotective Potential of Stem\/Stromal Cells Derived from Adipose Tissue. Cells, 10.","DOI":"10.3390\/cells10061475"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1038\/jcbfm.2012.190","article-title":"Subfield-specific neurovascular remodeling in the entorhino-hippocampal-organotypic slice culture as a response to oxygen-glucose deprivation and excitotoxic cell death","volume":"33","author":"Chip","year":"2012","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1523\/JNEUROSCI.2700-13.2014","article-title":"BDNF mediates neuroprotection against oxygen-glucose deprivation by the cardiac glycoside oleandrin","volume":"34","author":"He","year":"2014","journal-title":"J. Neurosci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.brainres.2014.03.037","article-title":"GPR30 activation is neither necessary nor sufficient for acute neuroprotection by 17\u03b2-estradiol after an ischemic injury in organotypic hippocampal slice cultures","volume":"1563","author":"Lamprecht","year":"2014","journal-title":"Brain Res."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Trojan, E., Tylek, K., Le\u015bkiewicz, M., Laso\u0144, W., Brandenburg, L.-O., Leopoldo, M., Lacivita, E., and Basta-Kaim, A. (2021). The N-Formyl Peptide Receptor 2 (FPR2) Agonist MR-39 Exhibits Anti-Inflammatory Activity in LPS-Stimulated Organotypic Hippocampal Cultures. Cells, 10.","DOI":"10.3390\/cells10061524"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/0165-0270(94)00147-9","article-title":"Quantitative measurement of neuronal degeneration in organotypic hippocampal cultures after combined oxygen\/glucose deprivation","volume":"57","author":"Strasser","year":"1995","journal-title":"J. Neurosci. Methods"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1038\/aps.2016.108","article-title":"15-Deoxy-\u039412,14-prostaglandin J2 alleviates hepatic ischemia-reperfusion injury in mice via inducing antioxidant response and inhibiting apoptosis and autophagy","volume":"38","author":"Chen","year":"2017","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_44","first-page":"82","article-title":"Prenatal stress is a vulnerability factor for altered morphology and biological activity of microglia cells","volume":"9","author":"Trojan","year":"2015","journal-title":"Front. Cell. Neurosci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1152\/physrev.00029.2006","article-title":"Nitric oxide and peroxynitrite in health and disease","volume":"87","author":"Pacher","year":"2007","journal-title":"Physiol. Rev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"319","DOI":"10.2174\/1568007054546126","article-title":"Role of nitric oxide and calpain activation in neuronal death and survival","volume":"4","author":"Araujo","year":"2005","journal-title":"Curr. Drug Target-CNS Neurol. Disord."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1089\/jir.2005.25.297","article-title":"Review: Hypoxia-inducible factor-1 (HIF-1): A novel transcription factor in immune reactions","volume":"25","author":"Stiehl","year":"2005","journal-title":"J. Interf. Cytokine Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/S0304-3940(98)00688-0","article-title":"Induction of hypoxia inducible factor 1 by oxygen glucose deprivation is attenuated by hypoxic preconditioning in rat cultured neurons","volume":"254","author":"Ruscher","year":"1998","journal-title":"Neurosci. Lett."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1159\/000495879","article-title":"HIF1\u03b1 Signaling in the Endogenous Protective Responses after Neonatal Brain Hypoxia-Ischemia","volume":"40","author":"Liang","year":"2018","journal-title":"Dev. Neurosci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1007\/978-3-211-85578-2_77","article-title":"HIF-1 alpha inhibition ameliorates neonatal brain damage after hypoxic-ischemic injury","volume":"102","author":"Chen","year":"2008","journal-title":"Acta Neurochir. Suppl."},{"key":"ref_51","first-page":"100916","article-title":"A simple method for quantitating confocal fluorescent images","volume":"25","author":"Shihan","year":"2021","journal-title":"Biochem. Biophys. Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1007\/s12975-021-00888-3","article-title":"The Key Regulator of Necroptosis, RIP1 Kinase, Contributes to the Formation of Astrogliosis and Glial Scar in Ischemic Stroke","volume":"12","author":"Zhu","year":"2021","journal-title":"Transl. Stroke Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1007\/s10753-018-0914-4","article-title":"Neuronal EphA4 Regulates OGD\/R-Induced Apoptosis by Promoting Alternative Activation of Microglia","volume":"42","author":"Wei","year":"2018","journal-title":"Inflammation"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"725268","DOI":"10.3389\/fphar.2021.725268","article-title":"MLIF Modulates Microglia Polarization in Ischemic Stroke by Targeting eEF1A1","volume":"12","author":"Liu","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4051","DOI":"10.1007\/s12035-021-02372-3","article-title":"The Cytoskeletal Elements MAP2 and NF-L Show Substantial Alterations in Different Stroke Models While Elevated Serum Levels Highlight Especially MAP2 as a Sensitive Biomarker in Stroke Patients","volume":"58","author":"Mages","year":"2021","journal-title":"Mol. Neurobiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1097\/00004647-199904000-00008","article-title":"Upregulation of MAP1B and MAP2 in the rat brain after middle cerebral artery occlusion: Effect of age","volume":"19","author":"Schmoll","year":"1999","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1369\/0022155419878181","article-title":"Morphological Characteristics of Neuronal Death After Experimental Subarachnoid Hemorrhage in Mice Using Double Immunoenzymatic Technique","volume":"67","author":"Nakano","year":"2019","journal-title":"J. Histochem. Cytochem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1016\/S0306-4522(99)00079-2","article-title":"DNA cleavage and proteolysis of microtubule-associated protein 2 after cerebral ischemia of different severity","volume":"92","author":"Yagita","year":"1999","journal-title":"Neuroscience"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.jchemneu.2016.09.004","article-title":"Up-regulation of neurofilament light chains is associated with diminished immunoreactivities for MAP2 and tau after ischemic stroke in rodents and in a human case","volume":"78","author":"Krueger","year":"2016","journal-title":"J. Chem. Neuroanat."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1097\/00004647-199611000-00013","article-title":"Microtubular proteolysis in focal cerebral ischemia","volume":"16","author":"Pettigrew","year":"1996","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3389\/fnsyn.2016.00003","article-title":"The Roles of Microtubule-Based Transport at Presynaptic Nerve Terminals","volume":"8","author":"Yagensky","year":"2016","journal-title":"Front. Synaptic Neurosci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"146297","DOI":"10.1016\/j.brainres.2019.06.016","article-title":"The temporal and spatial changes of actin cytoskeleton in the hippocampal CA1 neurons following transient global ischemia","volume":"1720","author":"Guo","year":"2019","journal-title":"Brain Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"16276","DOI":"10.1038\/s41598-022-20623-8","article-title":"Changes in nanomechanical properties of single neuroblastoma cells as a model for oxygen and glucose deprivation (OGD)","volume":"12","author":"Pabijan","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1007\/s43440-021-00315-2","article-title":"The emerging role of mechanical and topographical factors in the development and treatment of nervous system disorders: Dark and light sides of the force","volume":"73","author":"Kubiak","year":"2021","journal-title":"Pharmacol. Rep."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"6212","DOI":"10.1039\/D0NR06464E","article-title":"Stiffening of DU145 prostate cancer cells driven by actin filaments\u2014Microtubule crosstalk conferring resistance to microtubule-targeting drugs","volume":"13","author":"Kubiak","year":"2021","journal-title":"Nanoscale"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.brainres.2009.11.087","article-title":"Rho kinase inhibition protects CA1 cells in organotypic hippocampal slices during in vitro ischemia","volume":"1316","author":"Gisselsson","year":"2010","journal-title":"Brain Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2623","DOI":"10.4103\/1673-5374.335827","article-title":"Advantages of Rho-associated kinases and their inhibitor fasudil for the treatment of neurodegenerative diseases","volume":"17","author":"Xiao","year":"2022","journal-title":"Neural Regen. Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"3256","DOI":"10.1038\/s41467-021-23482-5","article-title":"Mechanically activated ion channel Piezo1 modulates macrophage polarization and stiffness sensing","volume":"12","author":"Atcha","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_69","unstructured":"Bryniarska-Kubiak, N., Kubiak, A., and Basta-Kaim, A. (2022). Mechanotransductive receptor Piezo1 as a promising target in the treatment of neurological diseases. Curr. Neuropharmacol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"709620","DOI":"10.3389\/fnagi.2021.709620","article-title":"A Shift in Tissue Stiffness During Hippocampal Maturation Correlates to the Pattern of Neurogenesis and Composition of the Extracellular Matrix","volume":"13","author":"Ryu","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.jneumeth.2016.07.002","article-title":"Brain tissue stiffness is a sensitive marker for acidosis","volume":"271","author":"Holtzmann","year":"2016","journal-title":"J. Neurosci. Methods"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Ishihara, S., and Haga, H. (2022). Matrix Stiffness Contributes to Cancer Progression by Regulating Transcription Factors. Cancers, 14.","DOI":"10.3390\/cancers14041049"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"H169","DOI":"10.1152\/ajpheart.00205.2018","article-title":"Central artery stiffness and thoracic aortopathy","volume":"316","author":"Humphrey","year":"2019","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"17511","DOI":"10.1038\/s41598-017-17787-z","article-title":"Substrate stiffness influences phenotype and function of human antigen-presenting dendritic cells","volume":"7","author":"Mennens","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1002\/jbm.a.34104","article-title":"The effects of substrate stiffness on the in vitro activation of macrophages and in vivo host response to poly(ethylene glycol)-based hydrogels","volume":"100","author":"Blakney","year":"2012","journal-title":"J. Biomed. Mater. Res. Part A"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Previtera, M.L., and Sengupta, A. (2015). Substrate Stiffness Regulates Proinflammatory Mediator Production through TLR4 Activity in Macrophages. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0145813"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"5908","DOI":"10.1073\/pnas.1811516116","article-title":"Biphasic mechanosensitivity of T cell receptor-mediated spreading of lymphocytes","volume":"116","author":"Wahl","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.1016\/j.bpj.2021.02.042","article-title":"Rapid viscoelastic changes are a hallmark of early leukocyte activation","volume":"120","author":"Zak","year":"2021","journal-title":"Biophys. J."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/11\/1465\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:41:18Z","timestamp":1760125278000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/11\/1465"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,24]]},"references-count":78,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["cells12111465"],"URL":"https:\/\/doi.org\/10.3390\/cells12111465","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,24]]}}}