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The hippocampus is responsible for memory formation. As a functional core area, the cornu ammonis 1 (CA1) region of the hippocampus contains abundant blood vessels and is susceptible to ischemia. The aim of the study was to explore vascular function and neuronal state in the CA1 region of rats undergoing intraoperative hypothermia. The neuronal morphological change and activity-regulated cytoskeleton-associated protein (Arc) expression were evaluated by haematoxylin-eosin staining and immunofluorescence respectively. Histology and immunohistochemistry were used to assess vascular function. Results showed that intraoperative hypothermia inhibited the expression of vascular endothelial growth factor and endothelial nitric oxide synthase, and caused reactive oxygen species accumulation. Additionally, the phenotype of vascular smooth muscle cells was transformed from contractile to synthetic, showing a decrease in smooth muscle myosin heavy chain and an increase in osteopontin. Ultimately, vascular dysfunction caused neuronal pyknosis in the CA1 region and reduced memory-related Arc expression. In conclusion, neuronal disorder in the CA1 region was caused by intraoperative hypothermia-related vascular dysfunction. This study could provide a novel understanding of the effect of intraoperative hypothermia in the hippocampus, which might identify a new research target and treatment strategy.<\/jats:p>","DOI":"10.3390\/brainsci12060692","type":"journal-article","created":{"date-parts":[[2022,5,27]],"date-time":"2022-05-27T07:05:07Z","timestamp":1653635107000},"page":"692","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Intraoperative Hypothermia Induces Vascular Dysfunction in the CA1 Region of Rat Hippocampus"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6354-4481","authenticated-orcid":false,"given":"Tianjia","family":"Li","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7051-1189","authenticated-orcid":false,"given":"Guangyan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1977-2647","authenticated-orcid":false,"given":"Jie","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9278-6316","authenticated-orcid":false,"given":"Yuguang","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.ygyno.2013.08.034","article-title":"Intraoperative hypothermia during primary surgical cytoreduction for advanced ovarian cancer: Risk factors and associations with postoperative morbidity","volume":"131","author":"Long","year":"2013","journal-title":"Gynecol. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e14103","DOI":"10.1111\/ijcp.14103","article-title":"The incidence of inadvertent perioperative hypothermia in patients undergoing general anesthesia and an examination of risk factors","volume":"75","author":"Sari","year":"2021","journal-title":"Int. J. Clin. Pract."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1097\/ALN.0000000000000681","article-title":"Compliance with Surgical Care Improvement Project for Body Temperature Management (SCIP Inf-10) Is Associated with Improved Clinical Outcomes","volume":"123","author":"Scott","year":"2015","journal-title":"Anesthesiology"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Yi, J., Lei, Y., Xu, S., Si, Y., Li, S., Xia, Z., Shi, Y., Gu, X., Yu, J., and Xu, G. (2017). Intraoperative hypothermia and its clinical outcomes in patients undergoing general anesthesia: National study in China. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0177221"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"6696","DOI":"10.1111\/ejn.14958","article-title":"Arc\/Arg3.1 function in long-term synaptic plasticity: Emerging mechanisms and unresolved issues","volume":"54","author":"Zhang","year":"2021","journal-title":"Eur. J. Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Wang, D., Cui, Z., Zeng, Q., Kuang, H., Wang, L.P., Tsien, J.Z., and Cao, X. (2009). Genetic Enhancement of Memory and Long-Term Potentiation but Not CA1 Long-Term Depression in NR2B Transgenic Rats. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0007486"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"8443","DOI":"10.1523\/JNEUROSCI.20-22-08443.2000","article-title":"Dopamine and cAMP-regulated phosphoprotein 32 kDa controls both striatal long-term depression and long-term potentiation, opposing forms of synaptic plasticity","volume":"20","author":"Calabresi","year":"2000","journal-title":"J. Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.semcdb.2017.09.006","article-title":"Arc protein: A flexible hub for synaptic plasticity and cognition","volume":"77","author":"Nikolaienko","year":"2018","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1126\/science.287.5454.864","article-title":"Synaptic Assembly of the Brain in the Absence of Neurotransmitter Secretion","volume":"287","author":"Verhage","year":"2000","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1139\/cjpp-2020-0507","article-title":"Mild hyperhomocysteinemia induces blood\u2013brain barrier dysfunction but not neuroinflammation in the cerebral cortex and hippocampus of wild-type mice","volume":"99","author":"Chu","year":"2021","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.neuroscience.2016.04.011","article-title":"Changes in synaptic plasticity and expression of glutamate receptor subunits in the CA1 and CA3 areas of the hippocampus after transient global ischemia","volume":"327","author":"Han","year":"2016","journal-title":"Neuroscience"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1038\/nrn.2017.48","article-title":"Cerebral blood flow regulation and neurovascular dysfunction in Alzheimer disease","volume":"18","author":"Kisler","year":"2017","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1093\/nsr\/nwz124","article-title":"High-resolution mapping of brain vasculature and its impairment in the hippocampus of Alzheimer\u2019s disease mice","volume":"6","author":"Zhang","year":"2019","journal-title":"Natl. Sci. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/j.pharep.2018.03.004","article-title":"Ischemic tau protein gene induction as an additional key factor driving development of Alzheimer\u2019s phenotype changes in CA1 area of hippocampus in an ischemic model of Alzheimer\u2019s disease","volume":"70","author":"Pluta","year":"2018","journal-title":"Pharmacol. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Battaglia, S., Garofalo, S., and Di Pellegrino, G. (2018). Context-dependent extinction of threat memories: Influences of healthy aging. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-31000-9"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s11357-021-00449-4","article-title":"Hippocampus is more susceptible to hypoxic injury: Has the Rosetta Stone of regional variation in neurovascular coupling been deciphered?","volume":"44","author":"Zhang","year":"2022","journal-title":"Geroscience"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Estefan, D.P., S\u00e1nchez-Fibla, M., Duff, A., Principe, A., Rocamora, R., Zhang, H., Axmacher, N., and Verschure, P.F.M.J. (2019). Coordinated representational reinstatement in the human hippocampus and lateral temporal cortex during episodic memory retrieval. Nat. Commun., 10.","DOI":"10.1038\/s41467-019-09569-0"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1002\/mrm.22611","article-title":"Hippocampal blood flow in normal aging measured with arterial spin labeling at 3T","volume":"65","author":"Rusinek","year":"2011","journal-title":"Magn. Reson. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1038\/s41582-018-0031-x","article-title":"Spatial navigation deficits\u2014Overlooked cognitive marker for preclinical Alzheimer disease?","volume":"14","author":"Coughlan","year":"2018","journal-title":"Nat. Rev. Neurol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Hort, J., Vali\u0161, M., Ku\u010da, K., and Angelucci, F. (2019). Vascular Cognitive Impairment: Information from Animal Models on the Pathogenic Mechanisms of Cognitive Deficits. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20102405"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/j.freeradbiomed.2016.09.004","article-title":"Enhanced XOR activity in eNOS-deficient mice: Effects on the nitrate-nitrite-NO pathway and ROS homeostasis","volume":"99","author":"Peleli","year":"2016","journal-title":"Free Radic. Biol. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1016\/j.cell.2019.01.021","article-title":"VEGF in Signaling and Disease: Beyond Discovery and Development","volume":"176","author":"Apte","year":"2019","journal-title":"Cell"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Karaman, S., Lepp\u00e4nen, V.-M., and Alitalo, K. (2018). Vascular endothelial growth factor signaling in development and disease. Development, 145.","DOI":"10.1242\/dev.151019"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1093\/cvr\/cvs315","article-title":"Derivation and maturation of synthetic and contractile vascular smooth muscle cells from human pluripotent stem cells","volume":"97","author":"Wanjare","year":"2013","journal-title":"Cardiovasc. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s13239-014-0204-8","article-title":"Variation in Cardiac Pulse Frequencies Modulates vSMC Phenotype Switching During Vascular Remodeling","volume":"6","author":"Tosun","year":"2015","journal-title":"Cardiovasc. Eng. Technol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1016\/j.bbrc.2019.06.151","article-title":"The SR proteins SF2 and RBP1 regulate triglyceride storage in the fat body of Drosophila","volume":"516","author":"Bennick","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Monroe, D.G., Hawse, J.R., Subramaniam, M., and Spelsberg, T.C. (2010). Retinoblastoma binding protein-1 (RBP1) is a Runx2 coactivator and promotes osteoblastic differentiation. BMC Musculoskelet. Disord., 11.","DOI":"10.1186\/1471-2474-11-104"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.neuron.2017.07.030","article-title":"The Neurovascular Unit Coming of Age: A Journey through Neurovascular Coupling in Health and Disease","volume":"96","author":"Iadecola","year":"2017","journal-title":"Neuron"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Shaw, K., Bell, L., Boyd, K., Grijseels, D.M., Clarke, D., Bonnar, O., Crombag, H.S., and Hall, C.N. (2021). Neurovascular coupling and oxygenation are decreased in hippocampus compared to neocortex because of microvascular differences. Nat. Commun., 12.","DOI":"10.1038\/s41467-021-23508-y"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/nrn1387","article-title":"Neurovascular regulation in the normal brain and in Alzheimer\u2019s disease","volume":"5","author":"Iadecola","year":"2004","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.neuron.2014.12.032","article-title":"Blood-Brain Barrier Breakdown in the Aging Human Hippocampus","volume":"85","author":"Montagne","year":"2015","journal-title":"Neuron"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Senatorov, V.V., Friedman, A.R., Milikovsky, D.Z., Ofer, J., Saar-Ashkenazy, R., Charbash, A., Jahan, N., Chin, G., Mihaly, E., and Lin, J.M. (2019). Blood-brain barrier dysfunction in aging induces hyperactivation of TGF\u03b2 signaling and chronic yet reversible neural dysfunction. Sci. Transl. Med., 11.","DOI":"10.1126\/scitranslmed.aaw8283"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1002\/hipo.22802","article-title":"Selective decline of neurotrophin and neurotrophin receptor genes within CA1 pyramidal neurons and hippocampus proper: Correlation with cognitive performance and neuropathology in mild cognitive impairment and Alzheimer\u2019s disease","volume":"29","author":"Ginsberg","year":"2019","journal-title":"Hippocampus"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1002\/sctm.19-0174","article-title":"Exosomal 2\u2032,3\u2032-CNP from mesenchymal stem cells promotes hippocampus CA1 neurogenesis\/neuritogenesis and contributes to rescue of cognition\/learning deficiencies of damaged brain","volume":"9","author":"Chen","year":"2020","journal-title":"Stem Cells Transl. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1007\/s11011-020-00579-2","article-title":"Combination therapy of the granulocyte colony stimulating factor and intravenous lipid emulsion protect the hippocampus after global ischemia in rat: Focusing on CA1 region","volume":"35","author":"Rasouli","year":"2020","journal-title":"Metab. Brain Dis."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Lei, S., Zhang, P., Li, W., Gao, M., He, X., Zheng, J., Li, X., Wang, X., Wang, N., and Zhang, J. (2014). Pre- and Posttreatment With Edaravone Protects CA1 Hippocampus and Enhances Neurogenesis in the Subgranular Zone of Dentate Gyrus After Transient Global Cerebral Ischemia in Rats. ASN Neuro, 6.","DOI":"10.1177\/1759091414558417"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1016\/j.neuron.2018.05.012","article-title":"The Temporal Dynamics of Arc Expression Regulate Cognitive Flexibility","volume":"98","author":"Wall","year":"2018","journal-title":"Neuron"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/nn.2708","article-title":"New views of Arc, a master regulator of synaptic plasticity","volume":"14","author":"Shepherd","year":"2011","journal-title":"Nat. Neurosci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.neuron.2006.08.024","article-title":"Arc\/Arg3.1 Is Essential for the Consolidation of Synaptic Plasticity and Memories","volume":"52","author":"Plath","year":"2006","journal-title":"Neuron"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1021\/cn2001156","article-title":"Ischemia-Induced Increase in Microvascular Phosphodiesterase 4D Expression in Rat Hippocampus Associated with Blood Brain Barrier Permeability: Effect of Age","volume":"3","author":"He","year":"2012","journal-title":"ACS Chem. Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1038\/s41586-021-04369-3","article-title":"A human brain vascular atlas reveals diverse mediators of Alzheimer\u2019s risk","volume":"603","author":"Yang","year":"2022","journal-title":"Nature"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Xu, G., Li, T., and Huang, Y. (2022). The Effects of Intraoperative Hypothermia on Postoperative Cognitive Function in the Rat Hippocampus and Its Possible Mechanisms. Brain Sci., 12.","DOI":"10.3390\/brainsci12010096"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1038\/s41593-018-0118-0","article-title":"CA1 pyramidal cell diversity enabling parallel information processing in the hippocampus","volume":"21","author":"Soltesz","year":"2018","journal-title":"Nat. Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.freeradbiomed.2014.05.021","article-title":"Neurovascular coupling in hippocampus is mediated via diffusion by neuronal-derived nitric oxide","volume":"73","author":"Santos","year":"2014","journal-title":"Free Radic. Biol. Med."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Yi, J., Xiang, Z., Deng, X., Fan, T., Fu, R., Geng, W., Guo, R., He, N., Li, C., and Li, L. (2015). Incidence of Inadvertent Intraoperative Hypothermia and Its Risk Factors in Patients Undergoing General Anesthesia in Beijing: A Prospective Regional Survey. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0136136"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Yi, J., Zhan, L., Lei, Y., Xu, S., Si, Y., Li, S., Xia, Z., Shi, Y., Gu, X., and Yu, J. (2017). Establishment and Validation of a Prediction Equation to Estimate Risk of Intraoperative Hypothermia in Patients Receiving General Anesthesia. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-12997-x"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"18747","DOI":"10.3390\/ijms151018747","article-title":"Association between the Hypomethylation of Osteopontin and Integrin \u03b23 Promoters and Vascular Smooth Muscle Cell Phenotype Switching in Great Saphenous Varicose Veins","volume":"15","author":"Jiang","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1161\/01.RES.72.2.476","article-title":"Nitric oxide mediates vasodilatation in response to activation of N-methyl-D-aspartate receptors in brain","volume":"72","author":"Faraci","year":"1993","journal-title":"Circ. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"H1616","DOI":"10.1152\/ajpheart.2000.279.4.H1616","article-title":"P-450 epoxygenase and NO synthase inhibitors reduce cerebral blood flow response to N-methyl-d-aspartate","volume":"279","author":"Bhardwaj","year":"2000","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1006\/nimg.2002.1314","article-title":"Temporal Dynamics of Brain Tissue Nitric Oxide during Functional Forepaw Stimulation in Rats","volume":"18","author":"Buerk","year":"2003","journal-title":"NeuroImage"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2269","DOI":"10.1159\/000486061","article-title":"NLRP3 Gene Deletion Attenuates Angiotensin II-Induced Phenotypic Transformation of Vascular Smooth Muscle Cells and Vascular Remodeling","volume":"44","author":"Ren","year":"2017","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Cauli, B. (2010). Revisiting the role of neurons in neurovascular coupling. Front. Neuroenergetics, 2.","DOI":"10.3389\/fnene.2010.00009"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41591-018-0297-y","article-title":"Blood\u2013brain barrier breakdown is an early biomarker of human cognitive dysfunction","volume":"25","author":"Nation","year":"2019","journal-title":"Nat. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.bbrc.2016.10.027","article-title":"High glucose induces the expression of osteopontin in blood vessels in vitro and in vivo","volume":"480","author":"Li","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.bbrc.2016.09.106","article-title":"Perivascular adipose tissue alleviates inflammatory factors and stenosis in diabetic blood vessels","volume":"480","author":"Li","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/j.bbrc.2017.10.122","article-title":"Role of ROS-TRPM7-ERK1\/2 axis in high concentration glucose-mediated proliferation and phenotype switching of rat aortic vascular smooth muscle cells","volume":"494","author":"Yang","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1093\/brain\/awz383","article-title":"Hippocampal vascular reserve associated with cognitive performance and hippocampal volume","volume":"143","author":"Perosa","year":"2020","journal-title":"Brain"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"69","DOI":"10.3233\/JAD-150975","article-title":"Spatial Memory Impairment is Associated with Intraneural Amyloid-\u03b2 Immunoreactivity and Dysfunctional Arc Expression in the Hippocampal-CA3 Region of a Transgenic Mouse Model of Alzheimer\u2019s Disease","volume":"51","author":"Morin","year":"2016","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1111\/joa.13458","article-title":"Neuropeptides in the developing human hippocampus under hypoxic\u2013ischemic conditions","volume":"239","author":"Fuentes","year":"2021","journal-title":"J. Anat."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1161\/CIRCRESAHA.118.311378","article-title":"Mechanisms of Vascular Aging","volume":"123","author":"Ungvari","year":"2018","journal-title":"Circ. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"9158","DOI":"10.18632\/aging.202963","article-title":"Aging diabetes, deconstructing the cerebrovascular wall","volume":"13","author":"Fan","year":"2021","journal-title":"Aging"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Mughal, A., Harraz, O.F., Gonzales, A.L., Hill-Eubanks, D., and Nelson, M.T. (2021). PIP2 Improves Cerebral Blood Flow in a Mouse Model of Alzheimer\u2019s Disease. Function, 2.","DOI":"10.1093\/function\/zqab010"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1038\/nrn3114","article-title":"Neurovascular pathways to neurodegeneration in Alzheimer\u2019s disease and other disorders","volume":"12","author":"Zlokovic","year":"2011","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1016\/j.neuron.2013.10.008","article-title":"The Pathobiology of Vascular Dementia","volume":"80","author":"Iadecola","year":"2013","journal-title":"Neuron"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1038\/d41586-020-00131-3","article-title":"Neurodegenerative diseases distinguished through protein-structure analysis","volume":"578","author":"Gerez","year":"2020","journal-title":"Nature"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Shimizu, S., Hirose, D., Hatanaka, H., Takenoshita, N., Kaneko, Y., Ogawa, Y., Sakurai, H., and Hanyu, H. (2018). Role of Neuroimaging as a Biomarker for Neurodegenerative Diseases. Front. Neurol., 9.","DOI":"10.3389\/fneur.2018.00265"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Tanaka, M., Toldi, J., and V\u00e9csei, L. (2020). Exploring the Etiological Links behind Neurodegenerative Diseases: Inflammatory Cytokines and Bioactive Kynurenines. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21072431"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1007\/s12035-014-8657-1","article-title":"Body Fluid Cytokine Levels in Mild Cognitive Impairment and Alzheimer\u2019s Disease: A Comparative Overview","volume":"50","author":"Brosseron","year":"2014","journal-title":"Mol. Neurobiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"371","DOI":"10.2174\/1871527311312030010","article-title":"Drug-Induced Hypothermia in Stroke Models: Does it Always Protect?","volume":"12","author":"Zhang","year":"2013","journal-title":"CNS Neurol. Disord. -Drug Targets"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Curfman, G.D. (2002). Hypothermia to Protect the Brain. N. Engl. J. Med., 346.","DOI":"10.1056\/NEJM200202213460802"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/S1474-4422(03)00436-8","article-title":"Therapeutic hypothermia for acute stroke","volume":"2","author":"Olsen","year":"2003","journal-title":"Lancet Neurol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/nrn3174","article-title":"Neuroprotective mechanisms of hypothermia in brain ischaemia","volume":"13","author":"Yenari","year":"2012","journal-title":"Nat. Rev. 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