{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,15]],"date-time":"2026-03-15T04:11:57Z","timestamp":1773547917697,"version":"3.50.1"},"reference-count":63,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T00:00:00Z","timestamp":1753228800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T00:00:00Z","timestamp":1753228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"bijzonder onderzoeksfonds UHasselt Belgium","award":["21DOC21BOF"],"award-info":[{"award-number":["21DOC21BOF"]}]},{"name":"Bijzonder onderzoeksfonds UHasselt Belgium","award":["21KP06BOF"],"award-info":[{"award-number":["21KP06BOF"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Microglia, the primary phagocytes activated after spinal cord injury (SCI), play a key role in containing the lesion and protecting the glial scar from infiltrating immune cells. Although these responses are initially protective, excessive microglial proliferation and sustained pro-inflammatory activation can worsen secondary damage and limit recovery. Modulating microglial activity has been proposed as a potential therapeutic approach to enhance SCI repair. Previous studies suggest that constitutive loss of the mechanosensory channel TRPV4 (transient receptor potential vanilloid 4) reduces microgliosis and inflammation at the lesion site, improving functional outcomes. TRPV4 is a Ca<jats:sup>2+<\/jats:sup>-permeable channel implicated in several microglial characteristics, like morphology, motility, proliferation, and phagocytosis. Whereas endogenous TRPV4-activating stimuli are abundant at the lesion site, the microglia-specific contribution of TRPV4 in SCI recovery remains unknown. To investigate this, we used phagocyte-specific <jats:italic>Trpv4<\/jats:italic> conditional knockout mice and phagocyte-specific TRPV4-deficient bone marrow chimeras subjected to contusion SCI. We achieved robust and efficient spinal cord monocyte-derived cell repopulation after bone marrow transplantation and PLX treatment. Surprisingly, TRPV4 deficiency in phagocytes did not enhance functional recovery, reduce microgliosis, or diminish scar formation after SCI. Furthermore, contrary to prior studies, constitutive TRPV4 deficiency did not improve SCI outcomes, indicating that the role of TRPV4 in this context is complex and potentially redundant with other pathways.<\/jats:p>","DOI":"10.1038\/s41598-025-12372-1","type":"journal-article","created":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T11:38:55Z","timestamp":1753270735000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Loss of TRPV4 is insufficient to promote repair in a spinal cord injury contusion model"],"prefix":"10.1038","volume":"15","author":[{"given":"Melanie","family":"Mertens","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sofie","family":"Kessels","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naomi","family":"Veeningen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elle E. M.","family":"Scheijen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Femke","family":"Mussen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amber","family":"Delbroek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jana","family":"Van Broeckhoven","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yeranddy A.","family":"Alpizar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bert","family":"Br\u00f4ne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,7,23]]},"reference":[{"key":"12372_CR1","doi-asserted-by":"publisher","first-page":"1678","DOI":"10.4103\/1673-5374.389630","volume":"19","author":"S Brockie","year":"2024","unstructured":"Brockie, S., Zhou, C. & Fehlings, M. G. Resident immune responses to spinal cord injury: role of astrocytes and microglia. Neural Regen Res. 19, 1678\u20131685. https:\/\/doi.org\/10.4103\/1673-5374.389630 (2024).","journal-title":"Neural Regen Res."},{"key":"12372_CR2","doi-asserted-by":"publisher","unstructured":"Brockie, S., Hong, J. & Fehlings, M. G. The role of microglia in modulating neuroinflammation after spinal cord injury. Int. J. Mol. Sci. 22 https:\/\/doi.org\/10.3390\/ijms22189706 (2021).","DOI":"10.3390\/ijms22189706"},{"key":"12372_CR3","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1038\/s41593-020-0597-7","volume":"23","author":"X Zhou","year":"2020","unstructured":"Zhou, X. et al. Microglia and macrophages promote corralling, wound compaction and recovery after spinal cord injury via Plexin-B2. Nat. Neurosci. 23, 337\u2013350. https:\/\/doi.org\/10.1038\/s41593-020-0597-7 (2020).","journal-title":"Nat. Neurosci."},{"key":"12372_CR4","doi-asserted-by":"publisher","first-page":"752","DOI":"10.1038\/nn1472","volume":"8","author":"D Davalos","year":"2005","unstructured":"Davalos, D. et al. ATP mediates rapid microglial response to local brain injury in vivo. Nat. Neurosci. 8, 752\u2013758. https:\/\/doi.org\/10.1038\/nn1472 (2005).","journal-title":"Nat. Neurosci."},{"key":"12372_CR5","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1038\/s41467-019-08446-0","volume":"10","author":"V Bellver-Landete","year":"2019","unstructured":"Bellver-Landete, V. et al. Microglia are an essential component of the neuroprotective Scar that forms after spinal cord injury. Nat. Commun. 10, 518. https:\/\/doi.org\/10.1038\/s41467-019-08446-0 (2019).","journal-title":"Nat. Commun."},{"key":"12372_CR6","doi-asserted-by":"publisher","unstructured":"Deng, J. et al. Emerging roles of microglia depletion in the treatment of spinal cord injury. Cells 11 https:\/\/doi.org\/10.3390\/cells11121871 (2022).","DOI":"10.3390\/cells11121871"},{"key":"12372_CR7","doi-asserted-by":"publisher","first-page":"796704","DOI":"10.3389\/fneur.2021.796704","volume":"12","author":"L Xu","year":"2021","unstructured":"Xu, L., Wang, J., Ding, Y., Wang, L. & Zhu, Y. J. Current knowledge of microglia in traumatic spinal cord injury. Front. Neurol. 12, 796704. https:\/\/doi.org\/10.3389\/fneur.2021.796704 (2021).","journal-title":"Front. Neurol."},{"key":"12372_CR8","doi-asserted-by":"publisher","first-page":"11376","DOI":"10.7150\/thno.49199","volume":"10","author":"Y Li","year":"2020","unstructured":"Li, Y. et al. Delayed microglial depletion after spinal cord injury reduces chronic inflammation and neurodegeneration in the brain and improves neurological recovery in male mice. Theranostics 10, 11376\u201311403. https:\/\/doi.org\/10.7150\/thno.49199 (2020).","journal-title":"Theranostics"},{"key":"12372_CR9","doi-asserted-by":"publisher","first-page":"4096","DOI":"10.1038\/s41467-022-31797-0","volume":"13","author":"FH Brennan","year":"2022","unstructured":"Brennan, F. H. et al. Microglia coordinate cellular interactions during spinal cord repair in mice. Nat. Commun. 13, 4096. https:\/\/doi.org\/10.1038\/s41467-022-31797-0 (2022).","journal-title":"Nat. Commun."},{"key":"12372_CR10","doi-asserted-by":"publisher","first-page":"1387","DOI":"10.1038\/nn1997","volume":"10","author":"UK Hanisch","year":"2007","unstructured":"Hanisch, U. K. & Kettenmann, H. Microglia: Active sensor and versatile effector cells in the normal and pathologic brain. Nat. Neurosci. 10, 1387\u20131394. https:\/\/doi.org\/10.1038\/nn1997 (2007).","journal-title":"Nat. Neurosci."},{"key":"12372_CR11","doi-asserted-by":"publisher","unstructured":"Umpierre, A. D. et al. Microglial calcium signaling is attuned to neuronal activity in awake mice. Elife 9 https:\/\/doi.org\/10.7554\/eLife.56502 (2020).","DOI":"10.7554\/eLife.56502"},{"key":"12372_CR12","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1038\/nature07577","volume":"457","author":"C Wei","year":"2009","unstructured":"Wei, C. et al. Calcium flickers steer cell migration. Nature 457, 901\u2013905. https:\/\/doi.org\/10.1038\/nature07577 (2009).","journal-title":"Nature"},{"key":"12372_CR13","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1007\/s12640-016-9632-6","volume":"30","author":"S Echeverry","year":"2016","unstructured":"Echeverry, S., Rodriguez, M. J. & Torres, Y. P. Transient receptor potential channels in microglia: roles in physiology and disease. Neurotox. Res. 30, 467\u2013478. https:\/\/doi.org\/10.1007\/s12640-016-9632-6 (2016).","journal-title":"Neurotox. Res."},{"key":"12372_CR14","doi-asserted-by":"publisher","unstructured":"Vangeel, L. & Voets, T. Transient receptor potential channels and calcium signaling. Cold Spring Harb Perspect. Biol. 11 https:\/\/doi.org\/10.1101\/cshperspect.a035048 (2019).","DOI":"10.1101\/cshperspect.a035048"},{"key":"12372_CR15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/978-3-642-54215-2_1","volume":"222","author":"V Flockerzi","year":"2014","unstructured":"Flockerzi, V. & Nilius, B. TRPs: Truly remarkable proteins. Handb. Exp. Pharmacol. 222, 1\u201312. https:\/\/doi.org\/10.1007\/978-3-642-54215-2_1 (2014).","journal-title":"Handb. Exp. Pharmacol."},{"key":"12372_CR16","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1073\/pnas.0303329101","volume":"101","author":"J Vriens","year":"2004","unstructured":"Vriens, J. et al. Cell swelling, heat, and chemical agonists use distinct pathways for the activation of the cation channel TRPV4. Proc. Natl. Acad. Sci. U S A. 101, 396\u2013401. https:\/\/doi.org\/10.1073\/pnas.0303329101 (2004).","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"12372_CR17","doi-asserted-by":"publisher","unstructured":"Nishimoto, R. et al. Thermosensitive TRPV4 channels mediate temperature-dependent microglia movement. Proc. Natl. Acad. Sci. U S A. 118 https:\/\/doi.org\/10.1073\/pnas.2012894118 (2021).","DOI":"10.1073\/pnas.2012894118"},{"key":"12372_CR18","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1002\/glia.22306","volume":"60","author":"M Konno","year":"2012","unstructured":"Konno, M. et al. Stimulation of transient receptor potential vanilloid 4 channel suppresses abnormal activation of microglia induced by lipopolysaccharide. Glia 60, 761\u2013770. https:\/\/doi.org\/10.1002\/glia.22306 (2012).","journal-title":"Glia"},{"key":"12372_CR19","doi-asserted-by":"publisher","first-page":"1563","DOI":"10.1002\/glia.23979","volume":"69","author":"SN Redmon","year":"2021","unstructured":"Redmon, S. N. et al. TRPV4 channels mediate the mechanoresponse in retinal microglia. Glia 69, 1563\u20131582. https:\/\/doi.org\/10.1002\/glia.23979 (2021).","journal-title":"Glia"},{"key":"12372_CR20","doi-asserted-by":"publisher","first-page":"e11654","DOI":"10.1371\/journal.pone.0011654","volume":"5","author":"C Goswami","year":"2010","unstructured":"Goswami, C., Kuhn, J., Heppenstall, P. A. & Hucho, T. Importance of non-selective cation channel TRPV4 interaction with cytoskeleton and their reciprocal regulations in cultured cells. PLoS One. 5, e11654. https:\/\/doi.org\/10.1371\/journal.pone.0011654 (2010).","journal-title":"PLoS One"},{"key":"12372_CR21","doi-asserted-by":"publisher","first-page":"2157","DOI":"10.1002\/glia.24243","volume":"70","author":"J Beeken","year":"2022","unstructured":"Beeken, J. et al. Acute Inhibition of transient receptor potential vanilloid-type 4 cation channel halts cytoskeletal dynamism in microglia. Glia 70, 2157\u20132168. https:\/\/doi.org\/10.1002\/glia.24243 (2022).","journal-title":"Glia"},{"key":"12372_CR22","doi-asserted-by":"publisher","first-page":"1943","DOI":"10.1523\/JNEUROSCI.2035-19.2020","volume":"40","author":"H Kumar","year":"2020","unstructured":"Kumar, H. et al. Elevated TRPV4 levels contribute to endothelial damage and scarring in experimental spinal cord injury. J. Neurosci. 40, 1943\u20131955. https:\/\/doi.org\/10.1523\/JNEUROSCI.2035-19.2020 (2020).","journal-title":"J. Neurosci."},{"key":"12372_CR23","doi-asserted-by":"publisher","unstructured":"Anjum, A. et al. Spinal cord injury: Pathophysiology, multimolecular interactions, and underlying recovery mechanisms. Int. J. Mol. Sci. 21 https:\/\/doi.org\/10.3390\/ijms21207533 (2020).","DOI":"10.3390\/ijms21207533"},{"key":"12372_CR24","doi-asserted-by":"publisher","unstructured":"Munteanu, C. et al. Main cations and cellular biology of traumatic spinal cord injury. Cells 11 https:\/\/doi.org\/10.3390\/cells11162503 (2022).","DOI":"10.3390\/cells11162503"},{"key":"12372_CR25","doi-asserted-by":"publisher","first-page":"103953","DOI":"10.1016\/j.jmbbm.2020.103953","volume":"110","author":"HJ Baumann","year":"2020","unstructured":"Baumann, H. J. et al. Softening of the chronic hemi-section spinal cord injury Scar parallels dysregulation of cellular and extracellular matrix content. J. Mech. Behav. Biomed. Mater. 110, 103953. https:\/\/doi.org\/10.1016\/j.jmbbm.2020.103953 (2020).","journal-title":"J. Mech. Behav. Biomed. Mater."},{"key":"12372_CR26","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1084\/jem.29.3.235","volume":"29","author":"M Segale","year":"1919","unstructured":"Segale, M. The temperature of acutely inflamed peripheral tissue. J. Exp. Med. 29, 235\u2013249. https:\/\/doi.org\/10.1084\/jem.29.3.235 (1919).","journal-title":"J. Exp. Med."},{"key":"12372_CR27","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1038\/nri3843","volume":"15","author":"SS Evans","year":"2015","unstructured":"Evans, S. S., Repasky, E. A. & Fisher, D. T. Fever and the thermal regulation of immunity: The immune system feels the heat. Nat. Rev. Immunol. 15, 335\u2013349. https:\/\/doi.org\/10.1038\/nri3843 (2015).","journal-title":"Nat. Rev. Immunol."},{"key":"12372_CR28","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1038\/nm1082","volume":"10","author":"X Wang","year":"2004","unstructured":"Wang, X. et al. P2X7 receptor inhibition improves recovery after spinal cord injury. Nat. Med. 10, 821\u2013827. https:\/\/doi.org\/10.1038\/nm1082 (2004).","journal-title":"Nat. Med."},{"key":"12372_CR29","doi-asserted-by":"publisher","first-page":"3333","DOI":"10.1523\/JNEUROSCI.1216-11.2012","volume":"32","author":"C Huang","year":"2012","unstructured":"Huang, C. et al. Critical role of connexin 43 in secondary expansion of traumatic spinal cord injury. J. Neurosci. 32, 3333\u20133338. https:\/\/doi.org\/10.1523\/JNEUROSCI.1216-11.2012 (2012).","journal-title":"J. Neurosci."},{"key":"12372_CR30","doi-asserted-by":"publisher","unstructured":"Rodrigues, P., Ruviaro, N. A. & Trevisan, G. TRPV4 role in neuropathic pain mechanisms in rodents. Antioxid. (Basel). 12. https:\/\/doi.org\/10.3390\/antiox12010024 (2022).","DOI":"10.3390\/antiox12010024"},{"key":"12372_CR31","doi-asserted-by":"publisher","unstructured":"Hu, X. et al. A TRPV4-dependent neuroimmune axis in the spinal cord promotes neuropathic pain. J. Clin. Invest. 133 https:\/\/doi.org\/10.1172\/JCI161507 (2023).","DOI":"10.1172\/JCI161507"},{"key":"12372_CR32","doi-asserted-by":"publisher","first-page":"1014013","DOI":"10.3389\/fimmu.2022.1014013","volume":"13","author":"SP Fu","year":"2022","unstructured":"Fu, S. P. et al. Advances in the research of the role of macrophage\/microglia polarization-mediated inflammatory response in spinal cord injury. Front. Immunol. 13, 1014013. https:\/\/doi.org\/10.3389\/fimmu.2022.1014013 (2022).","journal-title":"Front. Immunol."},{"key":"12372_CR33","doi-asserted-by":"publisher","first-page":"1170","DOI":"10.1002\/glia.24164","volume":"70","author":"E Vankriekelsvenne","year":"2022","unstructured":"Vankriekelsvenne, E. et al. Transmembrane protein 119 is neither a specific nor a reliable marker for microglia. Glia 70, 1170\u20131190. https:\/\/doi.org\/10.1002\/glia.24164 (2022).","journal-title":"Glia"},{"key":"12372_CR34","doi-asserted-by":"publisher","first-page":"820127","DOI":"10.3389\/fncel.2022.820127","volume":"16","author":"D Mercurio","year":"2022","unstructured":"Mercurio, D. et al. Protein expression of the microglial marker Tmem119 decreases in association with morphological changes and location in a mouse model of traumatic brain injury. Front. Cell. Neurosci. 16, 820127. https:\/\/doi.org\/10.3389\/fncel.2022.820127 (2022).","journal-title":"Front. Cell. Neurosci."},{"key":"12372_CR35","doi-asserted-by":"publisher","first-page":"828115","DOI":"10.3389\/fimmu.2021.828115","volume":"12","author":"TN Nguyen","year":"2021","unstructured":"Nguyen, T. N., Siddiqui, G., Veldhuis, N. A. & Poole, D. P. Diverse roles of TRPV4 in macrophages: A need for unbiased profiling. Front. Immunol. 12, 828115. https:\/\/doi.org\/10.3389\/fimmu.2021.828115 (2021).","journal-title":"Front. Immunol."},{"key":"12372_CR36","doi-asserted-by":"publisher","first-page":"1627","DOI":"10.1084\/jem.20180247","volume":"215","author":"JC Cronk","year":"2018","unstructured":"Cronk, J. C. et al. Peripherally derived macrophages can engraft the brain independent of irradiation and maintain an identity distinct from microglia. J. Exp. Med. 215, 1627\u20131647. https:\/\/doi.org\/10.1084\/jem.20180247 (2018).","journal-title":"J. Exp. Med."},{"key":"12372_CR37","doi-asserted-by":"publisher","first-page":"108041","DOI":"10.1016\/j.celrep.2020.108041","volume":"32","author":"Z Xu","year":"2020","unstructured":"Xu, Z. et al. Efficient strategies for microglia replacement in the central nervous system. Cell. Rep. 32, 108041. https:\/\/doi.org\/10.1016\/j.celrep.2020.108041 (2020).","journal-title":"Cell. Rep."},{"key":"12372_CR38","doi-asserted-by":"publisher","first-page":"17018","DOI":"10.1038\/nrdp.2017.18","volume":"3","author":"CS Ahuja","year":"2017","unstructured":"Ahuja, C. S. et al. Traumatic spinal cord injury. Nat. Rev. Dis. Primers. 3, 17018. https:\/\/doi.org\/10.1038\/nrdp.2017.18 (2017).","journal-title":"Nat. Rev. Dis. Primers"},{"key":"12372_CR39","doi-asserted-by":"publisher","first-page":"e12","DOI":"10.1111\/j.1552-6569.2011.00629.x","volume":"22","author":"BC Healy","year":"2012","unstructured":"Healy, B. C. et al. Approaches to normalization of spinal cord volume: Application to multiple sclerosis. J. Neuroimag.. 22, e12\u201319. https:\/\/doi.org\/10.1111\/j.1552-6569.2011.00629.x (2012).","journal-title":"J. Neuroimaging"},{"key":"12372_CR40","doi-asserted-by":"publisher","first-page":"1544","DOI":"10.1038\/nn2015","volume":"10","author":"A Mildner","year":"2007","unstructured":"Mildner, A. et al. Microglia in the adult brain arise from Ly-6ChiCCR2\u2009+\u2009monocytes only under defined host conditions. Nat. Neurosci. 10, 1544\u20131553. https:\/\/doi.org\/10.1038\/nn2015 (2007).","journal-title":"Nat. Neurosci."},{"key":"12372_CR41","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1016\/j.bbrc.2022.04.032","volume":"611","author":"R Chakraborty","year":"2022","unstructured":"Chakraborty, R. & Goswami, C. Both heat-sensitive TRPV4 and cold-sensitive TRPM8 ion channels regulate microglial activity. Biochem. Biophys. Res. Commun. 611, 132\u2013139. https:\/\/doi.org\/10.1016\/j.bbrc.2022.04.032 (2022).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"12372_CR42","doi-asserted-by":"publisher","first-page":"368","DOI":"10.3389\/fncel.2018.00368","volume":"12","author":"YN Gerber","year":"2018","unstructured":"Gerber, Y. N. et al. CSF1R Inhibition reduces microglia proliferation, promotes tissue preservation and improves motor recovery after spinal cord injury. Front. Cell. Neurosci. 12, 368. https:\/\/doi.org\/10.3389\/fncel.2018.00368 (2018).","journal-title":"Front. Cell. Neurosci."},{"key":"12372_CR43","doi-asserted-by":"publisher","first-page":"4","DOI":"10.32607\/actanaturae.10934","volume":"12","author":"EA Kolos","year":"2020","unstructured":"Kolos, E. A. & Korzhevskii, D. E. Spinal cord microglia in health and disease. Acta Nat.. 12, 4\u201317. https:\/\/doi.org\/10.32607\/actanaturae.10934 (2020).","journal-title":"Acta Naturae"},{"key":"12372_CR44","doi-asserted-by":"publisher","first-page":"3568","DOI":"10.1523\/JNEUROSCI.2841-16.2017","volume":"37","author":"CM Freria","year":"2017","unstructured":"Freria, C. M. et al. Deletion of the fractalkine receptor, CX3CR1, improves endogenous repair, axon sprouting, and synaptogenesis after spinal cord injury in mice. J. Neurosci. 37, 3568\u20133587. https:\/\/doi.org\/10.1523\/JNEUROSCI.2841-16.2017 (2017).","journal-title":"J. Neurosci."},{"key":"12372_CR45","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1038\/nn1715","volume":"9","author":"AE Cardona","year":"2006","unstructured":"Cardona, A. E. et al. Control of microglial neurotoxicity by the fractalkine receptor. Nat. Neurosci. 9, 917\u2013924. https:\/\/doi.org\/10.1038\/nn1715 (2006).","journal-title":"Nat. Neurosci."},{"key":"12372_CR46","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1089\/neu.2006.23.635","volume":"23","author":"DM Basso","year":"2006","unstructured":"Basso, D. M. et al. Basso mouse scale for locomotion detects differences in recovery after spinal cord injury in five common mouse strains. J. Neurotrauma. 23, 635\u2013659. https:\/\/doi.org\/10.1089\/neu.2006.23.635 (2006).","journal-title":"J. Neurotrauma"},{"key":"12372_CR47","doi-asserted-by":"publisher","first-page":"714","DOI":"10.1038\/sc.2016.187","volume":"55","author":"M Sharif-Alhoseini","year":"2017","unstructured":"Sharif-Alhoseini, M. et al. Animal models of spinal cord injury: a systematic review. Spinal Cord. 55, 714\u2013721. https:\/\/doi.org\/10.1038\/sc.2016.187 (2017).","journal-title":"Spinal Cord"},{"key":"12372_CR48","doi-asserted-by":"publisher","first-page":"2201","DOI":"10.1002\/jnr.25120","volume":"100","author":"R Ridlen","year":"2022","unstructured":"Ridlen, R., McGrath, K. & Gorrie, C. A. Animal models of compression spinal cord injury. J. Neurosci. Res. 100, 2201\u20132212. https:\/\/doi.org\/10.1002\/jnr.25120 (2022).","journal-title":"J. Neurosci. Res."},{"key":"12372_CR49","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1038\/sc.2014.91","volume":"52","author":"T Cheriyan","year":"2014","unstructured":"Cheriyan, T. et al. Spinal cord injury models: a review. Spinal Cord. 52, 588\u2013595. https:\/\/doi.org\/10.1038\/sc.2014.91 (2014).","journal-title":"Spinal Cord"},{"key":"12372_CR50","doi-asserted-by":"publisher","first-page":"392","DOI":"10.3389\/fncel.2018.00392","volume":"12","author":"M Liu","year":"2018","unstructured":"Liu, M. et al. TRPV4 Inhibition improved myelination and reduced glia reactivity and inflammation in a Cuprizone-Induced mouse model of demyelination. Front. Cell. Neurosci. 12, 392. https:\/\/doi.org\/10.3389\/fncel.2018.00392 (2018).","journal-title":"Front. Cell. Neurosci."},{"key":"12372_CR51","doi-asserted-by":"publisher","unstructured":"Holloman, J. P. et al. Transient receptor potential vanilloid 4-Dependent microglial function in Myelin injury and repair. Int. J. Mol. Sci. 24 https:\/\/doi.org\/10.3390\/ijms242317097 (2023).","DOI":"10.3390\/ijms242317097"},{"key":"12372_CR52","doi-asserted-by":"publisher","first-page":"1310","DOI":"10.4049\/jimmunol.1901033","volume":"204","author":"RG Scheraga","year":"2020","unstructured":"Scheraga, R. G. et al. TRPV4 protects the lung from bacterial pneumonia via MAPK molecular pathway switching. J. Immunol. 204, 1310\u20131321. https:\/\/doi.org\/10.4049\/jimmunol.1901033 (2020).","journal-title":"J. Immunol."},{"key":"12372_CR53","doi-asserted-by":"publisher","first-page":"428","DOI":"10.4049\/jimmunol.1501688","volume":"196","author":"RG Scheraga","year":"2016","unstructured":"Scheraga, R. G. et al. TRPV4 mechanosensitive ion channel regulates Lipopolysaccharide-Stimulated macrophage phagocytosis. J. Immunol. 196, 428\u2013436. https:\/\/doi.org\/10.4049\/jimmunol.1501688 (2016).","journal-title":"J. Immunol."},{"key":"12372_CR54","doi-asserted-by":"publisher","first-page":"13698","DOI":"10.1073\/pnas.1735416100","volume":"100","author":"W Liedtke","year":"2003","unstructured":"Liedtke, W. & Friedman, J. M. Abnormal osmotic regulation in trpv4-\/- mice. Proc. Natl. Acad. Sci. U S A. 100, 13698\u201313703. https:\/\/doi.org\/10.1073\/pnas.1735416100 (2003).","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"12372_CR55","doi-asserted-by":"publisher","first-page":"4106","DOI":"10.1128\/MCB.20.11.4106-4114.2000","volume":"20","author":"S Jung","year":"2000","unstructured":"Jung, S. et al. Analysis of fractalkine receptor CX(3)CR1 function by targeted deletion and green fluorescent protein reporter gene insertion. Mol. Cell. Biol. 20, 4106\u20134114. https:\/\/doi.org\/10.1128\/MCB.20.11.4106-4114.2000 (2000).","journal-title":"Mol. Cell. Biol."},{"key":"12372_CR56","doi-asserted-by":"publisher","unstructured":"Gualdani, R. et al. Mechanical activation of TRPV4 channels controls albumin reabsorption by proximal tubule cells. Sci. Signal. 13 https:\/\/doi.org\/10.1126\/scisignal.abc6967 (2020).","DOI":"10.1126\/scisignal.abc6967"},{"key":"12372_CR57","doi-asserted-by":"publisher","first-page":"1596","DOI":"10.1016\/j.cell.2013.11.030","volume":"155","author":"CN Parkhurst","year":"2013","unstructured":"Parkhurst, C. N. et al. Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor. Cell 155, 1596\u20131609. https:\/\/doi.org\/10.1016\/j.cell.2013.11.030 (2013).","journal-title":"Cell"},{"key":"12372_CR58","doi-asserted-by":"publisher","first-page":"5976","DOI":"10.1038\/s41598-023-32633-1","volume":"13","author":"M Rossi","year":"2023","unstructured":"Rossi, M. et al. Warning regarding hematological toxicity of Tamoxifen activated CreERT2 in young Rosa26CreERT2 mice. Sci. Rep. 13, 5976. https:\/\/doi.org\/10.1038\/s41598-023-32633-1 (2023).","journal-title":"Sci. Rep."},{"key":"12372_CR59","doi-asserted-by":"publisher","DOI":"10.3791\/1488","author":"A Ray","year":"2010","unstructured":"Ray, A. & Dittel, B. N. Isolation of mouse peritoneal cavity cells. J. Vis. Exp. https:\/\/doi.org\/10.3791\/1488 (2010).","journal-title":"J. Vis. Exp."},{"key":"12372_CR60","doi-asserted-by":"publisher","first-page":"e70","DOI":"10.1002\/cpim.70","volume":"125","author":"CJ Bohlen","year":"2019","unstructured":"Bohlen, C. J., Bennett, F. C. & Bennett, M. L. Isolation and culture of microglia. Curr. Protoc. Immunol. 125, e70. https:\/\/doi.org\/10.1002\/cpim.70 (2019).","journal-title":"Curr. Protoc. Immunol."},{"key":"12372_CR61","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1038\/ncb1150","volume":"6","author":"VJ Bezzerides","year":"2004","unstructured":"Bezzerides, V. J., Ramsey, I. S., Kotecha, S., Greka, A. & Clapham, D. E. Rapid vesicular translocation and insertion of TRP channels. Nat. Cell. Biol. 6, 709\u2013720. https:\/\/doi.org\/10.1038\/ncb1150 (2004).","journal-title":"Nat. Cell. Biol."},{"key":"12372_CR62","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1084\/jem.20151437","volume":"213","author":"SA Levesque","year":"2016","unstructured":"Levesque, S. A. et al. Myeloid cell transmigration across the CNS vasculature triggers IL-1beta-driven neuroinflammation during autoimmune encephalomyelitis in mice. J. Exp. Med. 213, 929\u2013949. https:\/\/doi.org\/10.1084\/jem.20151437 (2016).","journal-title":"J. Exp. Med."},{"key":"12372_CR63","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/nmeth.2019","volume":"9","author":"J Schindelin","year":"2012","unstructured":"Schindelin, J. et al. Fiji: an open-source platform for biological-image analysis. Nat. Methods. 9, 676\u2013682. https:\/\/doi.org\/10.1038\/nmeth.2019 (2012).","journal-title":"Nat. Methods"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-12372-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-12372-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-12372-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T11:38:55Z","timestamp":1753270735000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-12372-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,23]]},"references-count":63,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["12372"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-12372-1","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,23]]},"assertion":[{"value":"6 December 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 July 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 July 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"26757"}}