{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T10:31:26Z","timestamp":1793442686435,"version":"4.5.0"},"reference-count":45,"publisher":"Radiation Research Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Radiation Research"],"published-print":{"date-parts":[[2021,2,5]]},"abstract":"<jats:p>Radiation-induced brain injury (RBI) is a serious complication in patients who have received radiotherapy for head and neck tumors. Currently, there is a scarcity of information on early diagnostic and preventive methods of RBI. Accumulating evidence suggests that microRNAs are involved in the regulation of radiation injury, but the molecular biological mechanism of miRNAs in RBI is largely unknown. Therefore, in our study, microRNA sequencing was used to discover differential miRNAs in the hippocampus of RBI-modeled mice, which suggested that miR-741-3p was most significantly upregulated. To clarify the underlying mechanism of miR-741-3p in RBI-modeled mice, an inhibitor of miR-741-3p (antagomiR-741) was delivered into the brain via the nasal passage before irradiation. The delivery of antagomiR-741 significantly reduced miR-741-3p levels in the hippocampus of RBI-modeled mice, and the cognitive dysfunction and neuronal apoptosis induced by radiation were also alleviated at 6 weeks postirradiation. Downregulation of miR-741-3p was found to improve the protrusion and branching status of microglia after irradiation and reduced the number of GFAP-positive astrocytes. Additionally, antagomiR-741 suppressed the radiation-induced production of pro-inflammatory cytokines IL-6 and TNF-\u03b1 in the hippocampus and S100B in the serum. Furthermore, Ddr2, PKC\u03b1 and St8sia1 were revealed as target genes of miR-741-3p and as potential regulatory targets for RBI. Overall, our study provides identification and functional evaluation of miRNA in RBI and lays the foundation for improving the prevention strategy for RBI based on the delivery of miRNA via the nose-brain pathway.<\/jats:p>","DOI":"10.1667\/rade-20-00070.1","type":"journal-article","created":{"date-parts":[[2021,3,31]],"date-time":"2021-03-31T07:11:06Z","timestamp":1617174666000},"page":"355-365","source":"Crossref","is-referenced-by-count":6,"title":["Nasal Delivery of AntagomiR-741 Protects Against the Radiation-Induced Brain Injury in Mice"],"prefix":"10.1667","volume":"195","author":[{"given":"Mingqian","family":"Ou","sequence":"first","affiliation":[{"name":"Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihao","family":"Fan","sequence":"additional","affiliation":[{"name":"Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Furong","family":"Sun","sequence":"additional","affiliation":[{"name":"Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minhua","family":"Li","sequence":"additional","affiliation":[{"name":"Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meijun","family":"Lin","sequence":"additional","affiliation":[{"name":"Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangsheng","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Puning People's Hospital, Southern Medical University, Jieyang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyun","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Luoding People's Hospital, Affiliated Hospital of Guangdong Medical University, Luoding, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haojie","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Southern Medical University, Affiliated Shenzhen Bao An Hospital, Shenzhen, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanxin","family":"Jie","sequence":"additional","affiliation":[{"name":"Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujie","family":"Cai","sequence":"additional","affiliation":[{"name":"Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Chen","sequence":"additional","affiliation":[{"name":"Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiongjin","family":"Chen","sequence":"additional","affiliation":[{"name":"Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Zhao","sequence":"additional","affiliation":[{"name":"The Intensive Care Unit, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei","family":"Tang","sequence":"additional","affiliation":[{"name":"Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Cui","sequence":"additional","affiliation":[{"name":"Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haihong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1243","reference":[{"key":"17","doi-asserted-by":"crossref","unstructured":"P Xu, Y Xu, B Hu, et al.  \"Brain Behav Immun.\"  50, \"Extracellular ATP enhances radiation-induced brain injury through microglial activation and paracrine signaling via P2X7 receptor.\" 87 (2015)","DOI":"10.1016\/j.bbi.2015.06.020"},{"key":"10","doi-asserted-by":"crossref","unstructured":"S Flamant  and R Tamarat  \"Radiat Res.\"  186, \"Extracellular vesicles and vascular injury: new insights for radiation exposure.\" 203 (2016)","DOI":"10.1667\/RR14482.1"},{"key":"15","doi-asserted-by":"crossref","unstructured":"VK Singh  and HB Pollard  \"Expert Rev Mol Diagn.\"  17, \"Ionizing radiation-induced altered microRNA expression as biomarkers for assessing acute radiation injury.\" 871 (2017)","DOI":"10.1080\/14737159.2017.1366316"},{"key":"3","doi-asserted-by":"crossref","unstructured":"L Yang, J Yang, G Li, et al.  \"Mol Neurobiol.\"  54, \"Pathophysiological responses in rat and mouse models of radiation-induced brain injury.\" 1022 (2017)","DOI":"10.1007\/s12035-015-9628-x"},{"key":"5","doi-asserted-by":"crossref","unstructured":"Y Xu, X Rong, W Hu, et al.  \"Int J Radiat Oncol Biol Phys.\"  101, \"Bevacizumab monotherapy reduces radiation-induced brain necrosis in nasopharyngeal carcinoma patients: a randomized controlled trial.\" 1087 (2018)","DOI":"10.1016\/j.ijrobp.2018.04.068"},{"key":"1","doi-asserted-by":"crossref","unstructured":"FS Ali, O Arevalo, S Zorofchian, et al.  \"Curr Oncol Rep.\"  21, \"Cerebral radiation necrosis: Incidence, pathogenesis, diagnostic challenges, and future opportunities.\" 66 (2019)","DOI":"10.1007\/s11912-019-0818-y"},{"key":"2","doi-asserted-by":"crossref","unstructured":"G Zanni, S Goto, AF Fragopoulou, et al.  \"Mol Psychiatry.\"  , \"Lithium treatment reverses irradiation-induced changes in rodent neural progenitors and rescues cognition.\"  (2019)","DOI":"10.1038\/s41380-019-0584-0"},{"key":"4","doi-asserted-by":"crossref","unstructured":"Y Yang, X Lin, J Li, et al.  \"Front Neurol.\"  10, \"Aberrant brain activity at early delay stage post-radiotherapy as a biomarker for predicting neurocognitive dysfunction late-delayed in patients with nasopharyngeal carcinoma.\" 752 (2019)","DOI":"10.3389\/fneur.2019.00752"},{"key":"6","doi-asserted-by":"crossref","unstructured":"M Genc, E Genc, BO Genc, et al.  \"Br J Radiol.\"  79, \"Significant response of radiation induced CNS toxicity to high dose steroid administration.\" e196 (2006)","DOI":"10.1259\/bjr\/50789043"},{"key":"7","doi-asserted-by":"crossref","unstructured":"GT Alfotih, MG Zheng, WQ Cai, et al.  \"Neurol Neurochir Pol.\"  50, \"Surgical techniques in radiation induced temporal lobe necrosis in nasopharyngeal carcinoma patients.\" 172 (2016)","DOI":"10.1016\/j.pjnns.2016.02.007"},{"key":"8","doi-asserted-by":"crossref","unstructured":"Z Schmal, A Isermann, D Hladik, et al.  \"Radiother Oncol.\"  137, \"DNA damage accumulation during fractionated low-dose radiation compromises hippocampal neurogenesis.\" 45 (2019)","DOI":"10.1016\/j.radonc.2019.04.021"},{"key":"9","doi-asserted-by":"crossref","unstructured":"H Chen, ZZ Chong, SM De Toledo, et al.  \"Brain Res.\"  1646, \"Delayed activation of human microglial cells by high dose ionizing radiation.\" 193 (2016)","DOI":"10.1016\/j.brainres.2016.06.002"},{"key":"11","doi-asserted-by":"crossref","unstructured":"MP Dragomir, E Knutsen, GA Calin,  \"Cell.\"  174, \"SnapShot: Unconventional miRNA functions.\" 1038 (2018)","DOI":"10.1016\/j.cell.2018.07.040"},{"key":"12","doi-asserted-by":"crossref","unstructured":"C Xiang, S Han, J Nao, et al.  \"Front Neurosci.\"  13, \"MicroRNAs dysregulation and metabolism in multiple system atrophy.\" 1103 (2019)","DOI":"10.3389\/fnins.2019.01103"},{"key":"13","doi-asserted-by":"crossref","unstructured":"H Yavarpour-Bali, M Ghasemi-Kasman, A Shojaei,  \"Prog Neuropsychopharmacol Biol Psychiatry.\"  98, \"Direct reprogramming of terminally differentiated cells into neurons: A novel and promising strategy for Alzheimer's disease treatment.\" 109820 (2020)","DOI":"10.1016\/j.pnpbp.2019.109820"},{"key":"14","doi-asserted-by":"crossref","unstructured":"F Ma, X Zhang, KJ Yin,  \"Exp Neurol.\"  323, \"MicroRNAs in central nervous system diseases: A prospective role in regulating blood-brain barrier integrity.\" 113094 (2020)","DOI":"10.1016\/j.expneurol.2019.113094"},{"key":"16","doi-asserted-by":"crossref","unstructured":"MA. Chaudhry,  \"J Cell Biochem.\"  115, \"Radiation-induced microRNA: discovery, functional analysis, and cancer radiotherapy.\" 436 (2014)","DOI":"10.1002\/jcb.24694"},{"key":"18","doi-asserted-by":"crossref","unstructured":"Y Peng, K Lu, Z Li, et al.  \"Neuro Oncol.\"  16, \"Blockade of Kv1.3 channels ameliorates radiation-induced brain injury.\" 528 (2014)","DOI":"10.1093\/neuonc\/not221"},{"key":"19","doi-asserted-by":"crossref","unstructured":"R. Morris,  \"J Neurosci Methods.\"  11, \"Developments of a water-maze procedure for studying spatial learning in the rat.\" 47 (1984)","DOI":"10.1016\/0165-0270(84)90007-4"},{"key":"20","doi-asserted-by":"crossref","unstructured":"V Agarwal, GW Bell, JW Nam, et al.  \"Elife.\"  4, \"Predicting effective microRNA target sites in mammalian mRNAs.\"  (2015)","DOI":"10.7554\/eLife.05005"},{"key":"21","doi-asserted-by":"crossref","unstructured":"IC Hoogland, C Houbolt, DJ van Westerloo, et al.  \"J Neuroinflammation.\"  12, \"Systemic inflammation and microglial activation: systematic review of animal experiments.\" 114 (2015)","DOI":"10.1186\/s12974-015-0332-6"},{"key":"22","doi-asserted-by":"crossref","unstructured":"M. Brenner,  \"Neurosci Lett.\"  565, \"Role of GFAP in CNS injuries.\" 7 (2014)","DOI":"10.1016\/j.neulet.2014.01.055"},{"key":"23","doi-asserted-by":"crossref","unstructured":"X Jin, Z Chen, X Liu, et al.  \"Brain Res.\"  1558, \"The expression of endothelial barrier antigen (EBA) and S100B in the rat parietal cortex following brain irradiation.\" 84 (2014)","DOI":"10.1016\/j.brainres.2014.02.032"},{"key":"24","doi-asserted-by":"crossref","unstructured":"V Anoop, LI Cutinho, P Mourya, et al.  \"Brain Res Bull.\"  155, \"Approaches for encephalic drug delivery using nanomaterials: The current status.\" 184 (2020)","DOI":"10.1016\/j.brainresbull.2019.11.017"},{"key":"25","doi-asserted-by":"crossref","unstructured":"AR Khan, M Liu, MW Khan, et al.  \"J Control Release.\"  268, \"Progress in brain targeting drug delivery system by nasal route.\" 364 (2017)","DOI":"10.1016\/j.jconrel.2017.09.001"},{"key":"26","doi-asserted-by":"crossref","unstructured":"F Erdo, LA Bors, D Farkas, et al.  \"Brain Res Bull.\"  143, \"Evaluation of intranasal delivery route of drug administration for brain targeting.\" 155 (2018)","DOI":"10.1016\/j.brainresbull.2018.10.009"},{"key":"27","doi-asserted-by":"crossref","unstructured":"Q Wang, Y Zhang, CH Wong, et al.  \"AAPS J.\"  20, \"Demonstration of direct nose-to-brain transport of unbound HIV-1 replication inhibitor DB213 via intranasal administration by pharmacokinetic modeling.\" 23 (2017)","DOI":"10.1208\/s12248-017-0179-0"},{"key":"28","doi-asserted-by":"crossref","unstructured":"MC Bonferoni  and S Rossi  \"Pharmaceutics.\"  11, \"Nanoemulsions for \u201cnose-to-brain\u201d drug delivery.\"  (2019)","DOI":"10.3390\/pharmaceutics11020084"},{"key":"29","doi-asserted-by":"crossref","unstructured":"E Eisenberg, R Goldman, D Schlag-Eisenberg, et al.  \"J Pain Res.\"  12, \"Adhesive arachnoiditis following lumbar epidural steroid injections: a report of two cases and review of the literature.\" 513 (2019)","DOI":"10.2147\/JPR.S192706"},{"key":"30","doi-asserted-by":"crossref","unstructured":"E Robinson, S Shahipasand, P Liantis, et al.  \"Br J Hosp Med (Lond).\"  79, \"Nerve root injection cancellations because of incomplete anticoagulation management.\" 465 (2018)","DOI":"10.12968\/hmed.2018.79.8.465"},{"key":"31","doi-asserted-by":"crossref","unstructured":"T Musumeci  and A Bonaccorso  \"Pharmaceutics.\"  11, \"Epilepsy disease and nose-to-brain delivery of polymeric nanoparticles: An overview.\" 118 (2019)","DOI":"10.3390\/pharmaceutics11030118"},{"key":"32","doi-asserted-by":"crossref","unstructured":"C Vitorino, S Silva, J Bicker, et al.  \"Drug Discov Today.\"  24, \"Antidepressants and nose-to-brain delivery: drivers, restraints, opportunities and challenges.\" 1911 (2019)","DOI":"10.1016\/j.drudis.2019.06.001"},{"key":"33","doi-asserted-by":"crossref","unstructured":"SV Dhuria, LR Hanson, WH Frey,  \"J Pharm Sci.\"  99, \"Intranasal delivery to the central nervous system: mechanisms and experimental considerations.\" 1654 (2010)","DOI":"10.1002\/jps.21924"},{"key":"34","doi-asserted-by":"crossref","unstructured":"H Tao, J Zhao, T Liu, et al.  \"Mediators Inflamm.\"  2017, \"Intranasal Delivery of miR-146a mimics delayed seizure onset in the lithium-pilocarpine mouse model.\" 6512620 (2017)","DOI":"10.1155\/2017\/6512620"},{"key":"35","doi-asserted-by":"crossref","unstructured":"TH Palpagama, HJ Waldvogel, RLM Faull, et al.  \"Front Mol Neurosci.\"  12, \"The role of microglia and astrocytes in Huntington's disease.\" 258 (2019)","DOI":"10.3389\/fnmol.2019.00258"},{"key":"36","doi-asserted-by":"crossref","unstructured":"N Yang, X Gao, X Qu, et al.  \"Radiat Res.\"  186, \"PIDD mediates radiation-induced microglia activation.\" 345 (2016)","DOI":"10.1667\/RR14374.1"},{"key":"37","doi-asserted-by":"crossref","unstructured":"GH Wang, Y Liu, XB Wu, et al.  \"Cytotherapy.\"  18, \"Neuroprotective effects of human umbilical cord-derived mesenchymal stromal cells combined with nimodipine against radiation-induced brain injury through inhibition of apoptosis.\" 53 (2016)","DOI":"10.1016\/j.jcyt.2015.10.006"},{"key":"38","doi-asserted-by":"crossref","unstructured":"A Serrano, S Apolloni, S Rossi, et al.  \"Cells.\"  8, \"The S100A4 Transcriptional inhibitor niclosamide reduces pro-inflammatory and migratory phenotypes of microglia: Implications for amyotrophic lateral sclerosis.\" 1261 (2019)","DOI":"10.3390\/cells8101261"},{"key":"39","doi-asserted-by":"crossref","unstructured":"CF Hatton  and CJA Duncan  \"Front Immunol.\"  10, \"Microglia are essential to protective antiviral immunity: Lessons from mouse models of viral encephalitis.\" 2656 (2019)","DOI":"10.3389\/fimmu.2019.02656"},{"key":"40","doi-asserted-by":"crossref","unstructured":"Z Fang, A Xu, L Wu, et al.  \"Sci Rep.\"  6, \"The role of protein kinase C alpha translocation in radiation-induced bystander effect.\" 25817 (2016)","DOI":"10.1038\/srep25817"},{"key":"41","doi-asserted-by":"crossref","unstructured":"M Hebron, M Peyton, X Liu, et al.  \"J Neuroimmunol.\"  311, \"Discoidin domain receptor inhibition reduces neuropathology and attenuates inflammation in neurodegeneration models.\" 1 (2017)","DOI":"10.1016\/j.jneuroim.2017.07.009"},{"key":"42","doi-asserted-by":"crossref","unstructured":"K Mlinac, D Fabris, Z Vukelic, et al.  \"Carbohydr Res.\"  382, \"Structural analysis of brain ganglioside acetylation patterns in mice with altered ganglioside biosynthesis.\" 1 (2013)","DOI":"10.1016\/j.carres.2013.09.007"},{"key":"43","doi-asserted-by":"crossref","unstructured":"CY Fong, CG Tay, LC Ong, et al.  \"Cochrane Database Syst Rev.\"  11, \"Chloral hydrate as a sedating agent for neurodiagnostic procedures in children.\" Cd011786 (2017)","DOI":"10.1002\/14651858.CD011786.pub2"},{"key":"44","doi-asserted-by":"crossref","unstructured":"I Roberts  and E Sydenham  \"Cochrane Database Syst Rev.\"  12, \"Barbiturates for acute traumatic brain injury.\" Cd000033 (2012)","DOI":"10.1002\/14651858.CD000033.pub2"},{"key":"45","unstructured":"K Tanobe, K Nishikawa, H Hinohara, et al.  \"Masui.\"  52, \"Blood-brain barrier and general anesthetics.\" 840 (2003)"}],"container-title":["Radiation Research"],"original-title":[],"deposited":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T09:45:22Z","timestamp":1793439922000},"score":1,"resource":{"primary":{"URL":"https:\/\/bioone.org\/journals\/radiation-research\/volume-195\/issue-4\/RADE-20-00070.1\/Nasal-Delivery-of-AntagomiR-741-Protects-Against-the-Radiation-Induced\/10.1667\/RADE-20-00070.1.full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,5]]},"references-count":45,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,4,1]]}},"URL":"https:\/\/doi.org\/10.1667\/rade-20-00070.1","relation":{},"ISSN":["0033-7587","1938-5404"],"issn-type":[{"value":"0033-7587","type":"print"},{"value":"1938-5404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,5]]}}}