{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T14:37:18Z","timestamp":1781534238812,"version":"3.54.5"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T00:00:00Z","timestamp":1654128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82001779"],"award-info":[{"award-number":["82001779"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Sepsis-associated encephalopathy (SAE) has been identified as a frequent complication of sepsis, featured by an aberrant level of cognitive and affective functions. The present study is designed to explore the changes in functional connectivity (FC) of the hippocampus in rats with SAE utilizing resting-state functional magnetic resonance imaging (rs-fMRI).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Sprague-Dawley rats were randomly assigned to the SAE and control groups. We acquired rs-fMRI data using a 7T MRI to evaluate hippocampal network functional differences between the two groups with a seed-based approach. Behavioral performance was assessed using the open field test and forced swimming test. Statistical analysis was undertaken to evaluate the correlation between the hippocampal FC and behavioral findings.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared with the control group, the SAE group showed increased FC between the bilateral hippocampus and thalamus, septum, bed nuclei stria terminalis (BNST), left primary forelimb somatosensory cortex (S1FL), primary motor cortex (M1), and inferior colliculus. Increased FC between the left hippocampus and thalamus, septum, BNST, left S1FL, and inferior colliculus was observed. While with the right hippocampus, FC in thalamus, septum, left S1FL and inferior colliculus was enhanced. Additionally, positive correlations were found between the hippocampal FC and the immobility time in the forced swimming test.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Hippocampus-related brain networks have significant alterations in rats with SAE, and the elevated hippocampal resting-state FC was positively related to affective deficits. Changes in FC between the hippocampus and other brain regions could be a potential neuroimaging biomarker of cognitive or mental disorders triggered by SAE.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnins.2022.894720","type":"journal-article","created":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T07:31:46Z","timestamp":1654155106000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Increased Resting-State Functional Connectivity of the Hippocampus in Rats With Sepsis-Associated Encephalopathy"],"prefix":"10.3389","volume":"16","author":[{"given":"Yue","family":"Yao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunqiang","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuihua","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xian","family":"Xian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhua","family":"Tong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2292","DOI":"10.1111\/j.1460-9568.2010.07251.x","article-title":"Hippocampal-anterior thalamic pathways for memory: uncovering a network of direct and indirect actions.","volume":"31","author":"Aggleton","year":"2010","journal-title":"Eur. J. Neurosci."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.99364","article-title":"Targeting inflammatory monocytes in sepsis-associated encephalopathy and long-term cognitive impairment.","volume":"3","author":"Andonegui","year":"2018","journal-title":"JCI Insight"},{"key":"B3","doi-asserted-by":"crossref","first-page":"12286","DOI":"10.1073\/pnas.1525309113","article-title":"Functional connectivity with the retrosplenial cortex predicts cognitive aging in rats.","volume":"113","author":"Ash","year":"2016","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-34002-9","article-title":"Sensorimotor stroke alters hippocampo-thalamic network activity.","volume":"8","author":"Baumgartner","year":"2018","journal-title":"Sci. Rep."},{"key":"B5","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1007\/s00213-018-5109-z","article-title":"Hippocampal network oscillations at the interplay between innate anxiety and learned fear.","volume":"236","author":"Caliskan","year":"2019","journal-title":"Psychopharmacology"},{"key":"B6","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1037\/a0031890","article-title":"Neocortical synaptic proliferation following forebrain-dependent trace associative learning.","volume":"127","author":"Chau","year":"2013","journal-title":"Behav. Neurosci."},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.594071","article-title":"Maf1 ameliorates sepsis-associated encephalopathy by suppressing the NF-kB\/NLRP3 inflammasome signaling pathway.","volume":"11","author":"Chen","year":"2020","journal-title":"Front. Immunol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1007\/s12640-009-9101-6","article-title":"Depressive-like parameters in sepsis survivor rats.","volume":"17","author":"Comim","year":"2010","journal-title":"Neurotox. Res."},{"key":"B9","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms2379","article-title":"Spatial organization of frequency preference and selectivity in the human inferior colliculus.","volume":"4","author":"De Martino","year":"2013","journal-title":"Nat. Commun."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/8841332","article-title":"Xiaoyao pills attenuate inflammation and nerve injury induced by lipopolysaccharide in hippocampal neurons in vitro.","volume":"2020","author":"Fang","year":"2020","journal-title":"Neural Plast."},{"key":"B11","doi-asserted-by":"publisher","first-page":"6062","DOI":"10.1523\/JNEUROSCI.5582-05.2006","article-title":"Vibrissa-signaled eyeblink conditioning induces somatosensory cortical plasticity.","volume":"26","author":"Galvez","year":"2006","journal-title":"J. Neurosci."},{"key":"B12","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1177\/0885066616673973","article-title":"Cerebral blood flow autoregulation in sepsis for the intensivist: why its monitoring may be the future of individualized care.","volume":"33","author":"Goodson","year":"2018","journal-title":"J. Intensive Care Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1038\/sj.npp.1300116","article-title":"Norepinephrine but not serotonin reuptake inhibitors enhance theta and gamma activity of the septo-hippocampal system.","volume":"28","author":"Hajos","year":"2003","journal-title":"Neuropsychopharmacology"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1294","DOI":"10.1093\/cercor\/bhr181","article-title":"Resting-state connectivity identifies distinct functional networks in macaque cingulate cortex.","volume":"22","author":"Hutchison","year":"2012","journal-title":"Cereb. Cortex"},{"key":"B15","doi-asserted-by":"publisher","first-page":"183","DOI":"10.5607\/en20056","article-title":"Preliminary comparison of subcortical structures in elderly subclinical depression: structural analysis with 3T MRI.","volume":"30","author":"Im","year":"2021","journal-title":"Exp. Neurobiol."},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0202661","article-title":"Altered functional connectivity within the default mode network in two animal models with opposing episodic memories.","volume":"13","author":"Ji","year":"2018","journal-title":"PLoS One"},{"key":"B17","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1002\/cne.22527","article-title":"Decline in adult neurogenesis during aging follows a topographic pattern in the mouse hippocampus.","volume":"519","author":"Jinno","year":"2011","journal-title":"J Comp. Neurol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1097\/WNR.0b013e328334884c","article-title":"A novel method for olfactory bulbectomy using photochemically induced lesion.","volume":"21","author":"Kang","year":"2010","journal-title":"Neuroreport"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1186\/s12888-018-1913-6","article-title":"Functional connectivity between the thalamus and the primary somatosensory cortex in major depressive disorder: a resting-state fMRI study.","volume":"18","author":"Kang","year":"2018","journal-title":"BMC Psychiatry"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1150","DOI":"10.7150\/ijbs.12044","article-title":"Beneficial effects of highly palatable food on the behavioral and neural adversities induced by early life stress experience in female rats.","volume":"11","author":"Kim","year":"2015","journal-title":"Int. J. Biol. Sci."},{"key":"B21","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1038\/mp.2016.1","article-title":"Overshadowed by the amygdala: the bed nucleus of the stria terminalis emerges as key to psychiatric disorders.","volume":"21","author":"Lebow","year":"2016","journal-title":"Mol. Psychiatry"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1282","DOI":"10.1016\/j.neuroimage.2009.09.072","article-title":"Reliability of fMRI motor tasks in structures of the corticostriatal circuitry: implications for future studies and circuit function.","volume":"49","author":"Lee","year":"2010","journal-title":"Neuroimage"},{"key":"B23","doi-asserted-by":"publisher","first-page":"3517","DOI":"10.1002\/hbm.22418","article-title":"Neuronal oscillations and functional interactions between resting state networks.","volume":"35","author":"Lei","year":"2014","journal-title":"Hum. Brain Mapp."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1207","DOI":"10.1002\/jmri.27195","article-title":"structural and functional thalamic changes in Parkinson\u2019s disease with mild cognitive impairment.","volume":"52","author":"Li","year":"2020","journal-title":"J. Magn. Reson. Imaging"},{"key":"B25","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1089\/brain.2020.0875","article-title":"An investigation of the impacts of three anesthetic regimens on task-functional magnetic resonance imaging and functional connectivity resting-state functional magnetic resonance imaging in sprague Dawley and Wistar rats.","volume":"12","author":"Lu","year":"2021","journal-title":"Brain connect."},{"key":"B26","doi-asserted-by":"publisher","first-page":"3979","DOI":"10.1073\/pnas.1200506109","article-title":"Rat brains also have a default mode network.","volume":"109","author":"Lu","year":"2012","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B27","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.eplepsyres.2017.08.004","article-title":"Functional connectivity of the hippocampus to the thalamocortical circuitry in an animal model of absence seizures.","volume":"137","author":"Mousavi","year":"2017","journal-title":"Epilepsy Res."},{"key":"B28","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1016\/j.pnpbp.2009.03.039","article-title":"The septo-hippocampal system, learning and recovery of function.","volume":"33","author":"Niewiadomska","year":"2009","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"B29","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/j.bbr.2010.02.007","article-title":"Functional cooperation between the hippocampal subregions and the medial septum in unreinforced and reinforced spatial memory tasks.","volume":"209","author":"Okada","year":"2010","journal-title":"Behav. Brain Res."},{"key":"B30","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/j.bbi.2015.08.002","article-title":"NADPH oxidase 2-derived reactive oxygen species in the hippocampus might contribute to microglial activation in postoperative cognitive dysfunction in aged mice.","volume":"51","author":"Qiu","year":"2016","journal-title":"Brain Behav. Immun."},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1186\/1471-244X-12-32","article-title":"Impaired pitch identification as a potential marker for depression.","volume":"12","author":"Schwenzer","year":"2012","journal-title":"BMC Psychiatry"},{"key":"B32","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1016\/j.expneurol.2007.01.003","article-title":"Long-term cognitive impairment, neuronal loss and reduced cortical cholinergic innervation after recovery from sepsis in a rodent model.","volume":"204","author":"Semmler","year":"2007","journal-title":"Exp. Neurol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1136\/jnnp-2012-302883","article-title":"Persistent cognitive impairment, hippocampal atrophy and EEG changes in sepsis survivors.","volume":"84","author":"Semmler","year":"2013","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1799","DOI":"10.1016\/s0140-6736(03)14899-4","article-title":"Apoptosis of neurons in cardiovascular autonomic centres triggered by inducible nitric oxide synthase after death from septic shock.","volume":"362","author":"Sharshar","year":"2003","journal-title":"Lancet"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1353","DOI":"10.1177\/0898264318781123","article-title":"Depressive and anxiety symptoms in older adults with auditory, vision, and dual sensory impairment.","volume":"31","author":"Simning","year":"2019","journal-title":"J. Aging Health"},{"key":"B36","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.jpsychires.2017.06.006","article-title":"The impact of chronic mild stress on long-term depressive behavior in rats which have survived sepsis.","volume":"94","author":"Steckert","year":"2017","journal-title":"J. Psychiatr. Res."},{"key":"B37","doi-asserted-by":"publisher","first-page":"4076","DOI":"10.1002\/hbm.22899","article-title":"Resting state connectivity of the bed nucleus of the stria terminalis at ultra-high field.","volume":"36","author":"Torrisi","year":"2015","journal-title":"Hum. Brain Mapp."},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3389\/fninf.2011.00026","article-title":"An in vivo MRI template set for morphometry, tissue segmentation, and fMRI localization in rats.","volume":"5","author":"Valdes-Hernandez","year":"2011","journal-title":"Front. Neuroinform."},{"key":"B39","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1523\/JNEUROSCI.0479-18.2018","article-title":"The cognitive thalamus as a gateway to mental representations.","volume":"39","author":"Wolff","year":"2019","journal-title":"J. Neurosci."},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0064820","article-title":"Altered functional connectivity in an aged rat model of postoperative cognitive dysfunction: a study using resting-state functional MRI.","volume":"8","author":"Xie","year":"2013","journal-title":"PLoS One"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2019.01421","article-title":"White matter structural brain connectivity of young healthy individuals with high trait anxiety.","volume":"10","author":"Yang","year":"2019","journal-title":"Front. Neurol."},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-01970-7","article-title":"Knockdown of long non-coding RNA SOX2OT downregulates SOX2 to improve hippocampal neurogenesis and cognitive function in a mouse model of sepsis-associated encephalopathy.","volume":"17","author":"Yin","year":"2020","journal-title":"J. Neuroinflammation"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1187","DOI":"10.1093\/cercor\/bhp182","article-title":"Noninvasive functional and structural connectivity mapping of the human thalamocortical system.","volume":"20","author":"Zhang","year":"2010","journal-title":"Cereb. Cortex"}],"container-title":["Frontiers in Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2022.894720\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T07:31:50Z","timestamp":1654155110000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2022.894720\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,2]]},"references-count":43,"alternative-id":["10.3389\/fnins.2022.894720"],"URL":"https:\/\/doi.org\/10.3389\/fnins.2022.894720","relation":{},"ISSN":["1662-453X"],"issn-type":[{"value":"1662-453X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,2]]},"article-number":"894720"}}