{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T20:20:53Z","timestamp":1792095653955,"version":"4.4.0"},"reference-count":100,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T00:00:00Z","timestamp":1758240000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Local Initiative for Excellence Foundation","award":["K08NS110988"],"award-info":[{"award-number":["K08NS110988"]}]},{"name":"National Institutes of Health\/National Institute of Neurological Disorders and Stroke","award":["K08NS110988"],"award-info":[{"award-number":["K08NS110988"]}]},{"name":"University of Cincinnati","award":["K08NS110988"],"award-info":[{"award-number":["K08NS110988"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Traumatic brain injury (TBI) is a major source of disability worldwide, with cognitive and memory deficits being pervasive after injury. The hippocampus, a major structure involved in learning and memory, is particularly vulnerable to TBI, and cellular dysfunction within the hippocampal dentate gyrus is believed to be a major contributor to cognitive deficits after TBI. However, there is little known about the transcriptomic changes occurring directly within the dentate gyrus at subacute-to-chronic timepoints after TBI. To address this, we performed bulk RNA sequencing and single-nucleus RNA sequencing of the isolated dentate gyrus three weeks after lateral fluid percussion injury in male rats. We report here that there is evidence of an ongoing neuroinflammatory response marked by increased neuroinflammatory genes that implicate various neuroinflammatory pathways that are associated with a subset of microglia and astrocyte populations.<\/jats:p>","DOI":"10.3390\/ijms26189140","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T10:08:58Z","timestamp":1758276538000},"page":"9140","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Altered Neuroinflammatory Transcriptomic Profile in the Hippocampal Dentate Gyrus Three Weeks After Lateral Fluid Percussion Injury in Rats"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-8251-332X","authenticated-orcid":false,"given":"Anthony J.","family":"DeSana","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yara","family":"Alfawares","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roshni","family":"Khatri","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy M.","family":"Hopkins","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faith V.","family":"Best","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"McGuire","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7103-971X","authenticated-orcid":false,"given":"Laura B.","family":"Ngwenya","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA"},{"name":"Department of Neurology and Rehabilitation Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.3171\/2017.10.JNS17352","article-title":"Estimating the global incidence of traumatic brain injury","volume":"130","author":"Dewan","year":"2019","journal-title":"J. Neurosurg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.tem.2022.04.003","article-title":"Metabolic disorders on cognitive dysfunction after traumatic brain injury","volume":"33","author":"Lai","year":"2022","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"101530","DOI":"10.1016\/j.rehab.2021.101530","article-title":"The effectiveness of memory remediation strategies after traumatic brain injury: Systematic review and meta-analysis","volume":"64","author":"Lambez","year":"2021","journal-title":"Ann. Phys. Rehabil. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"36","DOI":"10.3109\/02699052.2011.635352","article-title":"Comparison of subjective cognitive complaints with neuropsychological tests in individuals with mild vs more severe traumatic brain injuries","volume":"26","author":"Jamora","year":"2012","journal-title":"Brain Inj."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"941","DOI":"10.3109\/02699052.2012.666365","article-title":"Determinants of subjective memory complaints in community-dwelling adults with mild-to-moderate traumatic brain injury","volume":"26","author":"Bay","year":"2012","journal-title":"Brain Inj."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"McGuire, J.L., Correll, E.A., Lowery, A.C., Rhame, K., Anwar, F.N., McCullumsmith, R.E., and Ngwenya, L.B. (2019). Pioglitazone improves working memory performance when administered in chronic TBI. Neurobiol. Dis., 132.","DOI":"10.1016\/j.nbd.2019.104611"},{"key":"ref_7","first-page":"109","article-title":"Cognitive evaluation of traumatically brain-injured rats using serial testing in the Morris water maze","volume":"24","author":"Thompson","year":"2006","journal-title":"Restor. Neurol. Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1089\/neu.2006.23.1529","article-title":"Traumatic Brain Injury Produces Delay-Dependent Memory Impairment in Rats","volume":"23","author":"Whiting","year":"2006","journal-title":"J. Neurotrauma"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1089\/neu.1993.10.405","article-title":"Mild experimental brain injury in the rat induces cognitive deficits associated with regional neuronal loss in the hippocampus","volume":"10","author":"Hicks","year":"1993","journal-title":"J. Neurotrauma"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1002\/1097-4547(20010215)63:4<313::AID-JNR1025>3.0.CO;2-4","article-title":"Enhanced neurogenesis in the rodent hippocampus following traumatic brain injury","volume":"63","author":"Dash","year":"2001","journal-title":"J. Neurosci. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.ibneur.2020.11.005","article-title":"Deficits in pattern separation and dentate gyrus proliferation after rodent lateral fluid percussion injury","volume":"10","author":"Correll","year":"2021","journal-title":"IBRO Neurosci. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Ngwenya, L.B., and Danzer, S.C. (2018). Impact of Traumatic Brain Injury on Neurogenesis. Front. Neurosci., 12.","DOI":"10.3389\/fnins.2018.01014"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1038\/s41583-023-00710-z","article-title":"Assessments of dentate gyrus function: Discoveries and debates","volume":"24","author":"Borzello","year":"2023","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1016\/j.stemcr.2017.07.015","article-title":"Enhanced Dentate Neurogenesis after Brain Injury Undermines Long-Term Neurogenic Potential and Promotes Seizure Susceptibility","volume":"9","author":"Neuberger","year":"2017","journal-title":"Stem Cell Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5222","DOI":"10.1038\/s41467-024-49299-6","article-title":"Traumatic brain injury promotes neurogenesis at the cost of astrogliogenesis in the adult hippocampus of male mice","volume":"15","author":"Bielefeld","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_16","first-page":"65","article-title":"Widespread cellular proliferation and focal neurogenesis after traumatic brain injury in the rat","volume":"25","author":"Urrea","year":"2007","journal-title":"Restor. Neurol. Neurosci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1523\/JNEUROSCI.0993-19.2019","article-title":"Microglia Actively Remodel Adult Hippocampal Neurogenesis through the Phagocytosis Secretome","volume":"40","author":"Paris","year":"2020","journal-title":"J. Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1016\/j.neuron.2015.10.037","article-title":"Synaptic Integration of Adult-Born Hippocampal Neurons Is Locally Controlled by Astrocytes","volume":"88","author":"Sultan","year":"2015","journal-title":"Neuron"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1002\/glia.23505","article-title":"Unique role for dentate gyrus microglia in neuroblast survival and in VEGF-induced activation","volume":"67","author":"Kreisel","year":"2019","journal-title":"Glia"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1038\/s43587-022-00281-1","article-title":"Complement C1q-dependent excitatory and inhibitory synapse elimination by astrocytes and microglia in Alzheimer\u2019s disease mouse models","volume":"2","author":"Dejanovic","year":"2022","journal-title":"Nat. Aging"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1759091420911770","DOI":"10.1177\/1759091420911770","article-title":"Spatiotemporal Distribution of Microglia After Traumatic Brain Injury in Male Mice","volume":"12","author":"Caplan","year":"2020","journal-title":"ASN Neuro"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1347987","DOI":"10.1155\/2016\/1347987","article-title":"Astrocyte Hypertrophy Contributes to Aberrant Neurogenesis after Traumatic Brain Injury","volume":"2016","author":"Robinson","year":"2016","journal-title":"Neural Plast."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Littlejohn, E.L., DeSana, A.J., Williams, H.C., Chapman, R.T., Joseph, B., Juras, J.A., and Saatman, K.E. (2021). IGF1-Stimulated Posttraumatic Hippocampal Remodeling Is Not Dependent on mTOR. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.663456"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1038\/nrneurol.2017.13","article-title":"The far-reaching scope of neuroinflammation after traumatic brain injury","volume":"13","author":"Simon","year":"2017","journal-title":"Nat. Rev. Neurol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Boone, D.R., Weisz, H.A., Willey, H.E., Torres, K.E.O., Falduto, M.T., Sinha, M., Spratt, H., Bolding, I.J., Johnson, K.M., and Parsley, M.A. (2019). Traumatic brain injury induces long-lasting changes in immune and regenerative signaling. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0214741"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1089\/neur.2021.0021","article-title":"Transcriptional Pathology Evolves over Time in Rat Hippocampus after Lateral Fluid Percussion Traumatic Brain Injury","volume":"2","author":"Zdilar","year":"2021","journal-title":"Neurotrauma Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.ebiom.2017.01.046","article-title":"Traumatic Brain Injury Induces Genome-Wide Transcriptomic, Methylomic, and Network Perturbations in Brain and Blood Predicting Neurological Disorders","volume":"16","author":"Meng","year":"2017","journal-title":"EBioMedicine"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Xing, J., Ren, L., Xu, H., Zhao, L., Wang, Z.H., Hu, G.D., and Wei, Z.L. (2022). Single-Cell RNA Sequencing Reveals Cellular and Transcriptional Changes Associated With Traumatic Brain Injury. Front. Genet., 13.","DOI":"10.3389\/fgene.2022.861428"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e14913","DOI":"10.7717\/peerj.14913","article-title":"RNA-seq reveals Nup62 as a potential regulator for cell division after traumatic brain injury in mice hippocampus","volume":"11","author":"Zhao","year":"2023","journal-title":"PeerJ"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.3934\/mbe.2021065","article-title":"Integration of single-cell and bulk RNA sequencing data reveals key cell types and regulators in traumatic brain injury","volume":"18","author":"Zheng","year":"2021","journal-title":"Math. Biosci. Eng."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3894","DOI":"10.1038\/s41467-018-06222-0","article-title":"Single cell molecular alterations reveal target cells and pathways of concussive brain injury","volume":"9","author":"Arneson","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.expneurol.2018.12.003","article-title":"Significant changes in circular RNA in the mouse cerebral cortex around an injury site after traumatic brain injury","volume":"313","author":"Chen","year":"2019","journal-title":"Exp. Neurol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Puhakka, N., Bot, A.M., Vuokila, N., Debski, K.J., Lukasiuk, K., and Pitk\u00e4nen, A. (2017). Chronically dysregulated NOTCH1 interactome in the dentate gyrus after traumatic brain injury. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0172521"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.neuron.2007.01.025","article-title":"Decoding NMDA Receptor Signaling: Identification of Genomic Programs Specifying Neuronal Survival and Death","volume":"53","author":"Zhang","year":"2007","journal-title":"Neuron"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.neuroscience.2008.06.018","article-title":"Hypoxic\/ischemic conditions induce expression of the putative pro-death gene Clca1 via activation of extrasynaptic N-methyl-d-aspartate receptors","volume":"158","author":"Wahl","year":"2009","journal-title":"Neuroscience"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1016\/j.cell.2007.10.036","article-title":"The classical complement cascade mediates CNS synapse elimination","volume":"131","author":"Stevens","year":"2007","journal-title":"Cell"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/j.neuron.2012.03.026","article-title":"Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner","volume":"74","author":"Schafer","year":"2012","journal-title":"Neuron"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"6233","DOI":"10.1038\/s41467-022-33932-3","article-title":"Microglial debris is cleared by astrocytes via C4b-facilitated phagocytosis and degraded via RUBICON-dependent noncanonical autophagy in mice","volume":"13","author":"Zhou","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1002\/glia.23169","article-title":"Astrocyte-mediated synapse remodeling in the pathological brain","volume":"65","author":"Kim","year":"2017","journal-title":"Glia"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.bbi.2021.08.210","article-title":"Novel microglia-mediated mechanisms underlying synaptic loss and cognitive impairment after traumatic brain injury","volume":"98","author":"Krukowski","year":"2021","journal-title":"Brain Behav. Immun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/s41392-023-01588-0","article-title":"Microglia in neurodegenerative diseases: Mechanism and potential therapeutic targets","volume":"8","author":"Gao","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/s41583-022-00641-1","article-title":"Astrocyte contribution to dysfunction, risk and progression in neurodegenerative disorders","volume":"24","author":"Brandebura","year":"2023","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1186\/s13073-023-01249-5","article-title":"Annotation of cell types (ACT): A convenient web server for cell type annotation","volume":"15","author":"Quan","year":"2023","journal-title":"Genome Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1111\/j.0022-202X.2005.23673.x","article-title":"C1q: Its Functions within the Innate and Adaptive Immune Responses and its Role in Lupus Autoimmunity","volume":"125","author":"Sontheimer","year":"2005","journal-title":"J. Investig. Dermatol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/s13041-025-01197-8","article-title":"Targeting CD74 in microglia to modulate experimental cerebral ischemia and reperfusion injury: Insights from Single-Cell and bulk transcriptomics","volume":"18","author":"Cao","year":"2025","journal-title":"Mol. Brain"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Jahn, J., Bollensdorf, A., Kalischer, C., Piecha, R., Wei\u00df-M\u00fcller, J., Potru, P.S., Ru\u00df, T., and Spittau, B. (2022). Microglial CD74 Expression Is Regulated by TGF\u03b2 Signaling. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231810247"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"7466","DOI":"10.1523\/JNEUROSCI.0682-22.2022","article-title":"STAT1 Contributes to Microglial\/Macrophage Inflammation and Neurological Dysfunction in a Mouse Model of Traumatic Brain Injury","volume":"42","author":"Zhao","year":"2022","journal-title":"J. Neurosci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.neuron.2018.10.013","article-title":"Activity-Regulated Transcription: Bridging the Gap between Neural Activity and Behavior","volume":"100","author":"Yap","year":"2018","journal-title":"Neuron"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"D\u2019Sa, K., Guelfi, S., Vandrovcova, J., Reynolds, R.H., Zhang, D., Hardy, J., Bot\u00eda, J.A., Weale, M.E., Taliun, S.A.G., and Small, K.S. (2023). Analysis of subcellular RNA fractions demonstrates significant genetic regulation of gene expression in human brain post-transcriptionally. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-40324-0"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"19802","DOI":"10.1073\/pnas.1319700110","article-title":"RNA-sequencing from single nuclei","volume":"110","author":"Grindberg","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s12974-018-1066-z","article-title":"The role of the complement system in traumatic brain injury: A review","volume":"15","author":"Hammad","year":"2018","journal-title":"J. Neuroinflamm."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S0162-3109(97)80150-6","article-title":"Bacterial meningitis: Complement gene expression in the central nervous system","volume":"38","author":"Stahel","year":"1997","journal-title":"Immunopharmacology"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Alawieh, A., Elvington, A., and Tomlinson, S. (2015). Complement in the Homeostatic and Ischemic Brain. Front. Immunol., 6.","DOI":"10.3389\/fimmu.2015.00417"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1002\/glia.10153","article-title":"Microglia and inflammatory mechanisms in the clearance of amyloid beta peptide","volume":"40","author":"Rogers","year":"2002","journal-title":"Glia"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1146\/annurev-neuro-061010-113810","article-title":"The complement system: An unexpected role in synaptic pruning during development and disease","volume":"35","author":"Stephan","year":"2012","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1038\/sj.emboj.7601004","article-title":"Complement: A novel factor in basal and ischemia-induced neurogenesis","volume":"25","author":"Rahpeymai","year":"2006","journal-title":"EMBO J."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2824","DOI":"10.1002\/stem.225","article-title":"Complement-derived anaphylatoxin C3a regulates in vitro differentiation and migration of neural progenitor cells","volume":"27","author":"Shinjyo","year":"2009","journal-title":"Stem Cells"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3981","DOI":"10.1523\/JNEUROSCI.3617-10.2011","article-title":"Complement receptor 2 is expressed in neural progenitor cells and regulates adult hippocampal neurogenesis","volume":"31","author":"Moriyama","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1089\/08977150152725605","article-title":"Complement activation in the human brain after traumatic head injury","volume":"18","author":"Bellander","year":"2001","journal-title":"J. Neurotrauma"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/S0165-5728(96)00164-6","article-title":"Elevated levels of the complement components C3 and factor B in ventricular cerebrospinal fluid of patients with traumatic brain injury","volume":"73","author":"Kossmann","year":"1997","journal-title":"J. Neuroimmunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/jcbfm.1995.107","article-title":"Effect of soluble complement receptor-1 on neutrophil accumulation after traumatic brain injury in rats","volume":"15","author":"Kaczorowski","year":"1995","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1097\/01.WCB.0000084250.20114.2C","article-title":"Central nervous system-targeted complement inhibition mediates neuroprotection after closed head injury in transgenic mice","volume":"23","author":"Rancan","year":"2003","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1016\/j.expneurol.2006.01.033","article-title":"Pharmacological complement inhibition at the C3 convertase level promotes neuronal survival, neuroprotective intracerebral gene expression, and neurological outcome after traumatic brain injury","volume":"199","author":"Leinhase","year":"2006","journal-title":"Exp. Neurol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1186\/s12974-021-02197-w","article-title":"Traumatic brain injury results in unique microglial and astrocyte transcriptomes enriched for type I interferon response","volume":"18","author":"Todd","year":"2021","journal-title":"J. Neuroinflamm."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Izzy, S., Liu, Q., Fang, Z., Lule, S., Wu, L., Chung, J.Y., Sarro-Schwartz, A., Brown-Whalen, A., Perner, C., and Hickman, S.E. (2019). Time-Dependent Changes in Microglia Transcriptional Networks Following Traumatic Brain Injury. Front. Cell Neurosci., 13.","DOI":"10.3389\/fncel.2019.00307"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.brainres.2016.07.002","article-title":"Altered expression of long non-coding RNA and mRNA in mouse cortex after traumatic brain injury","volume":"1646","author":"Zhong","year":"2016","journal-title":"Brain Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1186\/s40478-021-01226-2","article-title":"Chronic complement dysregulation drives neuroinflammation after traumatic brain injury: A transcriptomic study","volume":"9","author":"Toutonji","year":"2021","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/s13073-017-0467-4","article-title":"A practical guide to single-cell RNA-sequencing for biomedical research and clinical applications","volume":"9","author":"Haque","year":"2017","journal-title":"Genome Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"52","DOI":"10.4132\/jptm.2022.12.19","article-title":"Perspectives on single-nucleus RNA sequencing in different cell types and tissues","volume":"57","author":"Kim","year":"2023","journal-title":"J. Pathol. Transl. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.jss.2019.08.024","article-title":"Microglia Adopt Longitudinal Transcriptional Changes After Traumatic Brain Injury","volume":"246","author":"Makinde","year":"2020","journal-title":"J. Surg. Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1126\/science.2549638","article-title":"Inhibition of postsynaptic PKC or CaMKII blocks induction but not expression of LTP","volume":"245","author":"Malinow","year":"1989","journal-title":"Science"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/S0896-6273(03)00428-8","article-title":"Selective regulation of neurite extension and synapse formation by the beta but not the alpha isoform of CaMKII","volume":"39","author":"Fink","year":"2003","journal-title":"Neuron"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1126\/science.1321493","article-title":"Impaired spatial learning in alpha-calcium-calmodulin kinase II mutant mice","volume":"257","author":"Silva","year":"1992","journal-title":"Science"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1038\/nn.2857","article-title":"A CaMKII\u03b2 signaling pathway at the centrosome regulates dendrite patterning in the brain","volume":"14","author":"Puram","year":"2011","journal-title":"Nat. Neurosci."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Borghi, R., Trivisano, M., Specchio, N., Tartaglia, M., and Compagnucci, C. (2023). Understanding the pathogenetic mechanisms underlying altered neuronal function associated with CAMK2B mutations. Neurosci. Biobehav. Rev., 152.","DOI":"10.1016\/j.neubiorev.2023.105299"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Paban, V., Ogier, M., Chambon, C., Fernandez, N., Davidsson, J., Risling, M., and Alescio-Lautier, B. (2016). Molecular gene expression following blunt and rotational models of traumatic brain injury parallel injuries associated with stroke and depression. J. Transl. Sci., 2.","DOI":"10.15761\/JTS.1000159"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Halpain, S., and Dehmelt, L. (2006). The MAP1 family of microtubule-associated proteins. Genome Biol., 7.","DOI":"10.1186\/gb-2006-7-6-224"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"14805","DOI":"10.1523\/JNEUROSCI.1161-10.2010","article-title":"Behavioral and cerebellar transmission deficits in mice lacking the autism-linked gene islet brain-2","volume":"30","author":"Giza","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.brainresbull.2023.03.007","article-title":"Are cytoskeleton changes observed in astrocytes functionally linked to aging?","volume":"196","author":"Villablanca","year":"2023","journal-title":"Brain Res. Bull."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1038\/s41593-020-00728-x","article-title":"Tau accumulation in astrocytes of the dentate gyrus induces neuronal dysfunction and memory deficits in Alzheimer\u2019s disease","volume":"23","author":"Richetin","year":"2020","journal-title":"Nat. Neurosci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1159\/000365548","article-title":"Patterns of Hippocampal Tau Pathology Differentiate Neurodegenerative Dementias","volume":"38","author":"Milenkovic","year":"2014","journal-title":"Dement. Geriatr. Cogn. Disord."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1089\/neu.2018.6348","article-title":"Traumatic Brain Injury Induces Tau Aggregation and Spreading","volume":"37","author":"Edwards","year":"2020","journal-title":"J. Neurotrauma"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1016\/j.neuron.2018.10.014","article-title":"Changes in the Synaptic Proteome in Tauopathy and Rescue of Tau-Induced Synapse Loss by C1q Antibodies","volume":"100","author":"Dejanovic","year":"2018","journal-title":"Neuron"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1007\/BF02293907","article-title":"An examination of the effect of six types of error perturbation on fifteen clustering algorithms","volume":"45","author":"Milligan","year":"1980","journal-title":"Psychometrika"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"108189","DOI":"10.1016\/j.celrep.2020.108189","article-title":"Single-Nucleus RNA-Seq Is Not Suitable for Detection of Microglial Activation Genes in Humans","volume":"32","author":"Thrupp","year":"2020","journal-title":"Cell Rep."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"e14997","DOI":"10.7554\/eLife.14997","article-title":"Hipposeq: A comprehensive RNA-seq database of gene expression in hippocampal principal neurons","volume":"5","author":"Cembrowski","year":"2016","journal-title":"eLife"},{"key":"ref_87","unstructured":"National Research Council (2011). Guide for the Care and Use of Laboratory Animals: Eighth Edition."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"115120","DOI":"10.1016\/j.expneurol.2024.115120","article-title":"Repetitive cortical spreading depolarizations are prolonged early after experimental traumatic brain injury","volume":"385","author":"Best","year":"2025","journal-title":"Exp. Neurol."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Hagihara, H., Toyama, K., Yamasaki, N., and Miyakawa, T. (2009). Dissection of hippocampal dentate gyrus from adult mouse. J. Vis. Exp., 1543.","DOI":"10.3791\/1543-v"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2995","DOI":"10.1038\/s41467-023-38785-y","article-title":"ExpressAnalyst: A unified platform for RNA-sequencing analysis in non-model species","volume":"14","author":"Liu","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Blighe, K., Rana, S., and Lewis, M. (2024). EnhancedVolcano: Publication-ready volcano plots with enhanced colouring and labeling. R Package Version 1.22.0.","DOI":"10.32614\/CRAN.package.ggvolcano"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2847","DOI":"10.1093\/bioinformatics\/btw313","article-title":"Complex heatmaps reveal patterns and correlations in multidimensional genomic data","volume":"32","author":"Gu","year":"2016","journal-title":"Bioinformatics"},{"key":"ref_93","unstructured":"Harvard Chan Bioinformatics Core (2024, July 01). Introduction to Single-Cell RNA-seq. Available online: https:\/\/github.com\/hbctraining."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/s41587-023-01767-y","article-title":"Dictionary learning for integrative, multimodal and scalable single-cell analysis","volume":"42","author":"Hao","year":"2024","journal-title":"Nat. Biotechnol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"giy083","DOI":"10.1093\/gigascience\/giy083","article-title":"Clustering trees: A visualization for evaluating clusterings at multiple resolutions","volume":"7","author":"Zappia","year":"2018","journal-title":"GigaScience"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/nbt.4096","article-title":"Integrating single-cell transcriptomic data across different conditions, technologies, and species","volume":"36","author":"Butler","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2153","DOI":"10.1002\/glia.23636","article-title":"Transcriptional control of myelination and remyelination","volume":"67","author":"Sock","year":"2019","journal-title":"Glia"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"4678","DOI":"10.1038\/s41467-022-32205-3","article-title":"Connecting omics signatures and revealing biological mechanisms with iLINCS","volume":"13","author":"Pilarczyk","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Chen, E.Y., Tan, C.M., Kou, Y., Duan, Q., Wang, Z., Meirelles, G.V., Clark, N.R., and Ma\u2019ayan, A. (2013). Enrichr: Interactive and collaborative HTML5 gene list enrichment analysis tool. BMC Bioinform., 14.","DOI":"10.1186\/1471-2105-14-128"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"D679","DOI":"10.1093\/nar\/gkad960","article-title":"WikiPathways 2024: Next generation pathway database","volume":"52","author":"Agrawal","year":"2024","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/18\/9140\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:48:48Z","timestamp":1760035728000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/18\/9140"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,19]]},"references-count":100,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["ijms26189140"],"URL":"https:\/\/doi.org\/10.3390\/ijms26189140","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,19]]}}}