{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T14:20:05Z","timestamp":1790864405746,"version":"4.1.0"},"reference-count":25,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11_suppl_1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2013,9,10]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>Paraplegia continues to complicate thoracoabdominal aortic interventions. The elusive mechanism of spinal cord ischemia\u2013reperfusion injury has delayed the development of pharmacological adjuncts. Microglia, the resident macrophages of the central nervous system, can have pathological responses after a variety of insults. This can occur through toll-like receptor 4 (TLR-4) in stroke models. We hypothesize that spinal cord ischemia\u2013reperfusion injury after aortic occlusion results from TLR-4\u2013mediated microglial activation in mice.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>TLR-4 mutant and wild-type mice underwent aortic occlusion for 5 minutes, followed by 60 hours of reperfusion when spinal cords were removed for analysis. Spinal cord cytokine production and microglial activation were assessed at 6 and 36 hours after surgery. Isolated microglia from mutant and wild-type mice were subjected to oxygen and glucose deprivation for 24 hours, after which the expression of TLR-4 and proinflammatory cytokines was analyzed. Mice without functional TLR-4 demonstrated decreased microglial activation and cytokine production and had preserved functional outcomes and neuronal viability after thoracic aortic occlusion. After oxygen and glucose deprivation, wild-type microglia had increased TLR-4 expression and production of proinflammatory cytokines.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>The absence of functional TLR-4 attenuated neuronal injury and microglial activation after thoracic aortic occlusion in mice. Furthermore, microglial upregulation of TLR-4 occurred after oxygen and glucose deprivation, and the absence of functional TLR-4 significantly attenuated the production of proinflammatory cytokines. In conclusion, TLR-4\u2013mediated microglia activation in the spinal cord after aortic occlusion is critical in the mechanism of paraplegia after aortic cross-clamping and may provide targets for pharmacological intervention.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.112.000024","type":"journal-article","created":{"date-parts":[[2013,9,12]],"date-time":"2013-09-12T21:37:10Z","timestamp":1379021830000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":83,"title":["Toll-Like Receptor 4\u2013Dependent Microglial Activation Mediates Spinal Cord Ischemia\u2013Reperfusion Injury"],"prefix":"10.1161","volume":"128","author":[{"given":"Marshall T.","family":"Bell","sequence":"first","affiliation":[{"name":"From the Departments of Cardiothoracic Surgery (M.T.B., V.A.A., J.C.C., K.A.F., F.G., X.M., P.D.S., M.J.W., D.A.F., T.B.R.) and Anesthesiology (F.P., P.S.H.), University of Colorado, Denver, CO."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferenc","family":"Puskas","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiothoracic Surgery (M.T.B., V.A.A., J.C.C., K.A.F., F.G., X.M., P.D.S., M.J.W., D.A.F., T.B.R.) and Anesthesiology (F.P., P.S.H.), University of Colorado, Denver, CO."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktor A.","family":"Agoston","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiothoracic Surgery (M.T.B., V.A.A., J.C.C., K.A.F., F.G., X.M., P.D.S., M.J.W., D.A.F., T.B.R.) and Anesthesiology (F.P., P.S.H.), University of Colorado, Denver, CO."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Joseph C.","family":"Cleveland","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiothoracic Surgery (M.T.B., V.A.A., J.C.C., K.A.F., F.G., X.M., P.D.S., M.J.W., D.A.F., T.B.R.) and Anesthesiology (F.P., P.S.H.), University of Colorado, Denver, CO."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten A.","family":"Freeman","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiothoracic Surgery (M.T.B., V.A.A., J.C.C., K.A.F., F.G., X.M., P.D.S., M.J.W., D.A.F., T.B.R.) and Anesthesiology (F.P., P.S.H.), University of Colorado, Denver, CO."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabia","family":"Gamboni","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiothoracic Surgery (M.T.B., V.A.A., J.C.C., K.A.F., F.G., X.M., P.D.S., M.J.W., D.A.F., T.B.R.) and Anesthesiology (F.P., P.S.H.), University of Colorado, Denver, CO."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paco S.","family":"Herson","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiothoracic Surgery (M.T.B., V.A.A., J.C.C., K.A.F., F.G., X.M., P.D.S., M.J.W., D.A.F., T.B.R.) and Anesthesiology (F.P., P.S.H.), University of Colorado, Denver, CO."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianzhong","family":"Meng","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiothoracic Surgery (M.T.B., V.A.A., J.C.C., K.A.F., F.G., X.M., P.D.S., M.J.W., D.A.F., T.B.R.) and Anesthesiology (F.P., P.S.H.), University of Colorado, Denver, CO."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip D.","family":"Smith","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiothoracic Surgery (M.T.B., V.A.A., J.C.C., K.A.F., F.G., X.M., P.D.S., M.J.W., D.A.F., T.B.R.) and Anesthesiology (F.P., P.S.H.), University of Colorado, Denver, CO."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Weyant","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiothoracic Surgery (M.T.B., V.A.A., J.C.C., K.A.F., F.G., X.M., P.D.S., M.J.W., D.A.F., T.B.R.) and Anesthesiology (F.P., P.S.H.), University of Colorado, Denver, CO."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Fullerton","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiothoracic Surgery (M.T.B., V.A.A., J.C.C., K.A.F., F.G., X.M., P.D.S., M.J.W., D.A.F., T.B.R.) and Anesthesiology (F.P., P.S.H.), University of Colorado, Denver, CO."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. Brett","family":"Reece","sequence":"additional","affiliation":[{"name":"From the Departments of Cardiothoracic Surgery (M.T.B., V.A.A., J.C.C., K.A.F., F.G., X.M., P.D.S., M.J.W., D.A.F., T.B.R.) and Anesthesiology (F.P., P.S.H.), University of Colorado, Denver, CO."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2008.02.047"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfk047"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22482"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00086.2006"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.3340\/jkns.2011.49.2.83"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00011.2010"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.31.1.208"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2006.23.635"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-4547(20000815)61:4<430::AID-JNR9>3.0.CO;2-3"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.111.080275"},{"key":"e_1_3_3_12_2","first-page":"1","article-title":"Ischemic dose-response in the spinal cord: both immediate and delayed paraplegia.","volume":"7","author":"Smith PD","year":"2011","unstructured":"Smith PD, Puskas F, Meng X, Cho D, Cleveland JC, Weyant MJ, Watkins MT, Fullerton D a, Reece TB. 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