{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T19:18:04Z","timestamp":1790104684622,"version":"4.0.1"},"reference-count":68,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K08NS125042"],"award-info":[{"award-number":["K08NS125042"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HD072455"],"award-info":[{"award-number":["R01 HD072455"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIH-NEI P30 EY002162\/EY037668"],"award-info":[{"award-number":["NIH-NEI P30 EY002162\/EY037668"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Background: Hypoxic\u2013ischemic (HI) brain injury triggers a dynamic, multi-phase response involving early microglial efferocytosis followed by extracellular matrix (ECM) deposition and scar formation. Arginase-1 (ARG1), a key enzyme in tissue repair, is implicated in both processes, yet its role in neonatal microglia remains poorly defined. We characterize ARG1-linked pathways in neonatal microglia, identifying distinct efferocytic and fibrotic phases post-HI. Methods: HI was induced in P9 mice using the Vannucci model, and brains were collected at 24 h (D1) and 5 days (D5). Spatially resolved single-cell transcriptomics (seqFISH) was performed using a targeted panel enriched for microglial, ARG1-pathway, efferocytosis, and profibrotic genes. Cell segmentation, clustering, and spatial mapping were conducted using Navigator and Seurat. Differential expression, GSEA, and enrichment analyses were used to identify time- and injury-dependent pathways. Results: Spatial transcriptomics identified 12 transcriptionally distinct cell populations with preserved neuroanatomical organization. HI caused the expansion of microglia and astrocytes and the loss of glutamatergic neurons by D5. Microglia rapidly activated regenerative and profibrotic programs\u2014including TGF-\u03b2, PI3K\u2013Akt, cytoskeletal remodeling, and migration\u2014driven by early DEGs such as Cd44, Reln, TGF-\u03b21, and Col1a2. By D5, microglia adopted a collagen-rich fibrotic state with an upregulation of Bgn, Col11a1, Anxa5, and Npy. Conclusion: Neonatal microglia transition from early efferocytic responses to later fibrotic remodeling after HI, driven by the persistent activation of PI3K\u2013Akt, TGF-\u03b2, and Wnt\/FZD4 pathways. These findings identify microglia as central regulators of neonatal scar formation and highlight therapeutic targets within ARG1-linked signaling.<\/jats:p>","DOI":"10.3390\/cells15030253","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T15:56:12Z","timestamp":1769615772000},"page":"253","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Temporal and Spatial Gene Expression Dynamics in Neonatal HI Hippocampus with Focus on Arginase"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7899-7248","authenticated-orcid":false,"given":"Michael A.","family":"Smith","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of California San Francisco, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eesha","family":"Natarajan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California San Francisco, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Lizama-Valenzuela","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California San Francisco, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Arnold","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California San Francisco, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Stroud","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California San Francisco, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4348-7069","authenticated-orcid":false,"given":"Amara","family":"Larpthaveesarp","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California San Francisco, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Alvira","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California San Francisco, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9740-405X","authenticated-orcid":false,"given":"Jeffrey R.","family":"Fineman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California San Francisco, San Francisco, CA 94143, USA"},{"name":"Initiative for Pediatric Drug and Device Development, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0560-9045","authenticated-orcid":false,"given":"Donna M.","family":"Ferriero","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California San Francisco, San Francisco, CA 94143, USA"},{"name":"Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA 94158, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emin","family":"Maltepe","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California San Francisco, San Francisco, CA 94143, USA"},{"name":"Department of Biomedical Sciences, University of California San Francisco, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California San Francisco, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana K.","family":"Mike","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California San Francisco, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Tetorou, K., Sisa, C., Iqbal, A., Dhillon, K., and Hristova, M. (2021). Current Therapies for Neonatal Hypoxic-Ischaemic and Infection-Sensitised Hypoxic-Ischaemic Brain Damage. Front. Synaptic Neurosci., 13.","DOI":"10.3389\/fnsyn.2021.709301"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2843","DOI":"10.1097\/CM9.0000000000003363","article-title":"Efferocytosis: A new therapeutic target for stroke","volume":"137","author":"Gao","year":"2024","journal-title":"Chin. Med. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1002\/glia.24490","article-title":"Long-term recruitment of peripheral immune cells to brain scars after a neonatal insult","volume":"72","author":"Bolini","year":"2024","journal-title":"Glia"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1152\/physrev.00037.2016","article-title":"Arginase: A Multifaceted Enzyme Important in Health and Disease","volume":"98","author":"Caldwell","year":"2018","journal-title":"Physiol. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Rath, M., M\u00fcller, I., Kropf, P., Closs, E.I., and Munder, M. (2014). Metabolism via Arginase or Nitric Oxide Synthase: Two Competing Arginine Pathways in Macrophages. Front. Immunol., 5.","DOI":"10.3389\/fimmu.2014.00532"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1039\/c8mt00248g","article-title":"The inhibitory role of intracellular free zinc in the regulation of Arg-1 expression in interleukin-4-induced activation of M2 microglia","volume":"10","author":"Aratake","year":"2018","journal-title":"Metallomics"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Yang, Z., and Ming, X.F. (2013). Arginase: The emerging therapeutic target for vascular oxidative stress and inflammation. Front. Immunol., 4.","DOI":"10.3389\/fimmu.2013.00149"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"8512","DOI":"10.1523\/JNEUROSCI.0728-06.2006","article-title":"Arginase 1 regulation of nitric oxide production is key to survival of trophic factor-deprived motor neurons","volume":"26","author":"Sahawneh","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/j.cmet.2020.01.001","article-title":"Macrophage Metabolism of Apoptotic Cell-Derived Arginine Promotes Continual Efferocytosis and Resolution of Injury","volume":"31","author":"Yurdagul","year":"2020","journal-title":"Cell Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3079","DOI":"10.1523\/JNEUROSCI.4012-15.2016","article-title":"Cyclic AMP and Polyamines Overcome Inhibition by Myelin-Associated Glycoprotein through eIF5A-Mediated Increases in p35 Expression and Activation of Cdk5","volume":"36","author":"He","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Szondi, D.C., Wong, J.K., Vardy, L.A., and Cruickshank, S.M. (2021). Arginase Signaling as a Key Player in Chronic Wound Pathophysiology and Healing. Front. Mol. Biosci., 8.","DOI":"10.3389\/fmolb.2021.773866"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"8904","DOI":"10.1523\/JNEUROSCI.1146-14.2014","article-title":"IL-4 Signaling Drives a Unique Arginase+\/IL-1\u03b2+ Microglia Phenotype and Recruits Macrophages to the Inflammatory CNS: Consequences of Age-Related Deficits in IL-4R\u03b1 after Traumatic Spinal Cord Injury","volume":"34","author":"Fenn","year":"2014","journal-title":"J. Neurosci."},{"key":"ref_13","unstructured":"Stratoulias, V., Ruiz, R., Kanatani, S., Osman, A.M., Armengol, J.A., Rodr\u00edguez-Moreno, A., Murgoci, A.-N., Garc\u00eda-Dom\u00ednguez, I., Keane, L., and V\u00e1zquez-Cabrera, G. (2021). ARG1+ microglia are critical for shaping cognition in female mice. bioRxiv."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1038\/s41390-020-0978-3","article-title":"Changes in arginase isoforms in a murine model of neonatal brain hypoxia-ischemia","volume":"89","author":"Mike","year":"2021","journal-title":"Pediatr. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e25276","DOI":"10.1002\/jnr.25276","article-title":"Selective vulnerability of hippocampal CA1 and CA3 pyramidal cells: What are possible pathomechanisms and should more attention be paid to the CA3 region in future studies?","volume":"102","author":"Einenkel","year":"2024","journal-title":"J. Neurosci. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"608","DOI":"10.3345\/cep.2021.00164","article-title":"Cognitive outcomes in late childhood and adolescence of neonatal hypoxic-ischemic encephalopathy","volume":"64","author":"Lee","year":"2021","journal-title":"Clin. Exp. Pediatr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e131355","DOI":"10.1172\/jci.insight.131355","article-title":"STAT6\/ARG1 promotes microglia\/macrophage efferocytosis and inflammation resolution in stroke mice","volume":"4","author":"Cai","year":"2019","journal-title":"JCI Insight"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1111\/cns.13256","article-title":"Macrophages reprogram after ischemic stroke and promote efferocytosis and inflammation resolution in the mouse brain","volume":"25","author":"Zhang","year":"2019","journal-title":"CNS Neurosci. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Mike, J.K., and Ferriero, D.M. (2021). Efferocytosis Mediated Modulation of Injury after Neonatal Brain Hypoxia-Ischemia. Cells, 10.","DOI":"10.3390\/cells10051025"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"196","DOI":"10.3109\/08977194.2011.595714","article-title":"TGF-\u03b2 signaling in fibrosis","volume":"29","author":"Biernacka","year":"2011","journal-title":"Growth Factors"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2077","DOI":"10.4049\/jimmunol.155.4.2077","article-title":"Transforming growth factor-beta stimulates arginase activity in macrophages. Implications for the regulation of macrophage cytotoxicity","volume":"155","author":"Boutard","year":"1995","journal-title":"J. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Hamanaka, R.B., Shin, K.W.D., Atalay, M.V., Cetin-Atalay, R., Shah, H., Szafran, J.C.H., Woods, P.S., Meliton, A.Y., Shamaa, O.R., and Tian, Y. (2024). Role of Arginine and its Metabolism in TGF-\u03b2-Induced Activation of Lung Fibroblasts. bioRxiv.","DOI":"10.1101\/2024.11.01.618293"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1161\/01.CIR.103.8.1121","article-title":"Transforming Growth Factor-beta(1) Stimulates L-Arginine Transport and Metabolism in Vascular Smooth Muscle Cells","volume":"103","author":"Durante","year":"2001","journal-title":"Circulation"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1159\/000496467","article-title":"The Arginase Pathway in Neonatal Brain Hypoxia-Ischemia","volume":"40","author":"Krystofova","year":"2018","journal-title":"Dev. Neurosci."},{"key":"ref_25","first-page":"8","article-title":"Targeting TGF-\u03b2 signaling for the treatment of fibrosis","volume":"68\u201369","author":"Matei","year":"2018","journal-title":"Matrix Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1161\/ATVBAHA.121.316233","article-title":"Crosstalk Between Macrophages and Vascular Smooth Muscle Cells in Atherosclerotic Plaque Stability","volume":"42","author":"Yurdagul","year":"2022","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Senavirathna, L.K., Liang, Y., Huang, C., Yang, X., Bamunuarachchi, G., Xu, D., Dang, Q., Sivasami, P., Vaddadi, K., and Munteanu, M.C. (2021). Long Noncoding RNA FENDRR Inhibits Lung Fibroblast Proliferation via a Reduction of \u03b2-Catenin. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22168536"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2909","DOI":"10.4103\/NRR.NRR-D-24-00715","article-title":"Brain scarring in infants: Immunological insights from a neonatal hypoxic-ischemic encephalopathy model","volume":"20","year":"2025","journal-title":"Neural Regen. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3573","DOI":"10.1016\/j.cell.2021.04.048","article-title":"Integrated analysis of multimodal single-cell data","volume":"184","author":"Hao","year":"2021","journal-title":"Cell"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Crowell, H.L., Soneson, C., Germain, P.-L., Calini, D., Collin, L., Raposo, C., Malhotra, D., and Robinson, M.D. (2020). On the discovery of subpopulation-specific state transitions from multi-sample multi-condition single-cell RNA sequencing data. bioRxiv.","DOI":"10.1101\/713412"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1023\/A:1010933404324","article-title":"Random Forests","volume":"45","author":"Breiman","year":"2001","journal-title":"Mach. Learn."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"George, A.F., Luo, X., Neidleman, J., Hoh, R., Vohra, P., Thomas, R., Shin, M.G., Lee, M.J., Blish, C.A., and Deeks, S.G. (2022). Deep Phenotypic Analysis of Blood and Lymphoid T and NK Cells From HIV+ Controllers and ART-Suppressed Individuals. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.803417"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Duclot, F., and Kabbaj, M. (2017). The Role of Early Growth Response 1 (EGR1) in Brain Plasticity and Neuropsychiatric Disorders. Front. Behav. Neurosci., 11.","DOI":"10.3389\/fnbeh.2017.00035"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.nbd.2013.11.005","article-title":"Genome-wide approaches reveal EGR1-controlled regulatory networks associated with neurodegeneration","volume":"63","author":"Koldamova","year":"2014","journal-title":"Neurobiol. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3220","DOI":"10.1172\/JCI90604","article-title":"Transcriptional control of microglia phenotypes in health and disease","volume":"127","author":"Holtman","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1038\/s41593-023-01326-3","article-title":"ARG1-expressing microglia show a distinct molecular signature and modulate postnatal development and function of the mouse brain","volume":"26","author":"Stratoulias","year":"2023","journal-title":"Nat. Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"eabd8811","DOI":"10.1126\/sciadv.abd8811","article-title":"Diversified transcriptional responses of myeloid and glial cells in spinal cord injury shaped by HDAC3 activity","volume":"7","author":"Wahane","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/s12974-025-03428-0","article-title":"Microglia efferocytosis: An emerging mechanism for the resolution of neuroinflammation in Alzheimer\u2019s disease","volume":"22","author":"Chen","year":"2025","journal-title":"J. Neuroinflamm."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"13749","DOI":"10.1038\/s41598-024-63464-3","article-title":"Cell adhesion molecule CD44 is dispensable for reactive astrocyte activation during prion disease","volume":"14","author":"Bradford","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Li, L., Sun, B., Harris, O.A., and Luo, J. (2024). TGF-\u03b2 Signaling in Microglia: A Key Regulator of Development, Homeostasis and Reactivity. Biomedicines, 12.","DOI":"10.3390\/biomedicines12112468"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1038\/s41401-024-01432-3","article-title":"A novel annexin dimer targets microglial phagocytosis of astrocytes to protect the brain-blood barrier after cerebral ischemia","volume":"46","author":"Tang","year":"2025","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"111301","DOI":"10.1016\/j.cellsig.2024.111301","article-title":"The positive role of transforming growth factor-\u03b21 in ischemic stroke","volume":"121","author":"Li","year":"2024","journal-title":"Cell. Signal."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"121713","DOI":"10.1016\/j.lfs.2023.121713","article-title":"RAGE pathways play an important role in regulation of organ fibrosis","volume":"323","author":"Liu","year":"2023","journal-title":"Life Sci."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Rojas, A., Lindner, C., Schneider, I., Gonzalez, I., and Uribarri, J. (2024). The RAGE Axis: A Relevant Inflammatory Hub in Human Diseases. Biomolecules, 14.","DOI":"10.3390\/biom14040412"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"pgad334","DOI":"10.1093\/pnasnexus\/pgad334","article-title":"A unique cell population expressing the Epithelial-Mesenchymal Transition-transcription factor Snail moderates microglial and astrocyte injury responses","volume":"2","author":"Karl","year":"2023","journal-title":"PNAS Nexus"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Piersma, B., Bank, R.A., and Boersema, M. (2015). Signaling in Fibrosis: TGF-\u03b2, WNT, and YAP\/TAZ Converge. Front. Med., 2.","DOI":"10.3389\/fmed.2015.00059"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Nallanthighal, S., Heiserman, J.P., and Cheon, D.J. (2021). Collagen Type XI Alpha 1 (COL11A1): A Novel Biomarker and a Key Player in Cancer. Cancers, 13.","DOI":"10.3390\/cancers13050935"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1186\/s12935-020-01232-9","article-title":"Arginine deprivation: A potential therapeutic for cancer cell metastasis? A review","volume":"20","author":"Maalouf","year":"2020","journal-title":"Cancer Cell Int."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Wright, B., King, S., and Suphioglu, C. (2024). The Importance of Phosphoinositide 3-Kinase in Neuroinflammation. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252111638"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Sennello, J.A., Flozak, A.S., Misharin, A.V., Gottardi, C.J., and Lam, A.P. (2017). Arginase 1 is negatively regulated by \u03b2-catenin signaling in the lung. bioRxiv.","DOI":"10.1101\/137539"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1038\/s42003-024-06202-9","article-title":"Wnt\/\u03b2-catenin signaling regulates amino acid metabolism through the suppression of CEBPA and FOXA1 in liver cancer cells","volume":"7","author":"Nakagawa","year":"2024","journal-title":"Commun. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Yang, Y., and Zhang, Z. (2020). Microglia and Wnt Pathways: Prospects for Inflammation in Alzheimer\u2019s Disease. Front. Aging Neurosci., 12.","DOI":"10.3389\/fnagi.2020.00110"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/S0006-8993(01)03371-6","article-title":"Neurodegeneration in the rat hippocampus and striatum after middle cerebral artery occlusion","volume":"929","author":"Butler","year":"2002","journal-title":"Brain Res."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Li, T., Zhao, J., and Gao, H. (2022). Depletion of ARG1-Positive Microglia\/Macrophages Exacerbates Cerebral Ischemic Damage by Facilitating the Inflammatory Response. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232113055"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1038\/s41467-021-21617-2","article-title":"Mitochondrial arginase-2 is essential for IL-10 metabolic reprogramming of inflammatory macrophages","volume":"12","author":"Dowling","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e2413484122","DOI":"10.1073\/pnas.2413484122","article-title":"Detrimental influence of Arginase-1 in infiltrating macrophages on poststroke functional recovery and inflammatory milieu","volume":"122","author":"Kim","year":"2025","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"eabb2119","DOI":"10.1126\/sciadv.abb2119","article-title":"Fate mapping via CCR2-CreER mice reveals monocyte-to-microglia transition in development and neonatal stroke","volume":"6","author":"Chen","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1038\/s41586-025-09449-2","article-title":"Dynamic fibroblast\u2013immune interactions shape recovery after brain injury","volume":"646","author":"Mroz","year":"2025","journal-title":"Nature"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2239","DOI":"10.1016\/j.celrep.2016.05.012","article-title":"Complexin 3 Increases the Fidelity of Signaling in a Retinal Circuit by Regulating Exocytosis at Ribbon Synapses","volume":"15","author":"Mortensen","year":"2016","journal-title":"Cell Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/s12974-020-01774-9","article-title":"Transcriptomic profiling of microglia and astrocytes throughout aging","volume":"17","author":"Pan","year":"2020","journal-title":"J. Neuroinflamm."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Hsiao, C.-C., Sankowski, R., Prinz, M., Smolders, J., Huitinga, I., and Hamann, J. (2021). GPCRomics of Homeostatic and Disease-Associated Human Microglia. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.674189"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1111\/jnc.15195","article-title":"Activation of neuronal Ras-related C3 botulinum toxin substrate 1 (Rac1) improves post-stroke recovery and axonal plasticity in mice","volume":"157","author":"Bu","year":"2021","journal-title":"J. Neurochem."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"G\u00f3mez Morillas, A., Besson, V.C., and Lerouet, D. (2021). Microglia and Neuroinflammation: What Place for P2RY12?. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22041636"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Mercurio, D., Fumagalli, S., Schafer, M.K., Pedragosa, J., Ngassam, L.D.C., Wilhelmi, V., Winterberg, S., Planas, A.M., Weihe, E., and De Simoni, M.G. (2022). 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.","DOI":"10.3389\/fncel.2022.820127"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"111","DOI":"10.4103\/0971-5851.158842","article-title":"Transforming growth factor-\u03b21 and TGF-\u03b22 act synergistically in the fibrotic pathway in oral submucous fibrosis: An immunohistochemical observation","volume":"36","author":"Kamath","year":"2015","journal-title":"Indian J. Med. Paediatr. Oncol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1016\/j.immuni.2017.10.007","article-title":"The Cytokine TGF-\u03b2 Promotes the Development and Homeostasis of Alveolar Macrophages","volume":"47","author":"Yu","year":"2017","journal-title":"Immunity"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"14828","DOI":"10.1016\/S0021-9258(17)36699-1","article-title":"Transforming growth factor-beta stimulates alpha 2(I) collagen gene expression through a cis-acting element that contains an Sp1-binding site","volume":"269","author":"Inagaki","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1186\/s12974-025-03495-3","article-title":"N-Lactoyl-Phenylalanine modulates lipid metabolism in microglia\/macrophage via the AMPK-PGC1\u03b1-PPAR\u03b3 pathway to promote recovery in mice with spinal cord injury","volume":"22","author":"Ying","year":"2025","journal-title":"J. Neuroinflamm."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/3\/253\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T08:22:13Z","timestamp":1769674933000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/3\/253"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,28]]},"references-count":68,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["cells15030253"],"URL":"https:\/\/doi.org\/10.3390\/cells15030253","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,28]]}}}