{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T17:01:24Z","timestamp":1787936484494,"version":"build-2784847793"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2001,1]]},"abstract":"<jats:p>\n            <jats:italic>Background and Purpose<\/jats:italic>\n            \u2014The complement cascade is activated after experimental intracerebral hemorrhage (ICH). It remains unclear, however, whether depleting the complement system will improve injury resulting from ICH. This study investigated the effects of systemic complement depletion on brain edema formation after ICH.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Methods<\/jats:italic>\n            \u2014Fifty-six pentobarbital-anesthetized Sprague-Dawley rats were used. Treatment animals were complement-depleted with cobra venom factor (CVF) (intraperitoneally). Control rats received an equal volume of saline injection (intraperitoneally). In both treatment and control rats, autologous blood (100 \u03bcL) was infused stereotaxically into the right basal ganglia. Rats were killed 2, 24, or 72 hours later for brain water, ion, and tumor necrosis factor-\u03b1 (TNF-\u03b1) measurements, for Western blot analysis, and for immunohistochemical studies. Brain edema was quantitated by wet\/dry weight. TNF-\u03b1 levels were measured by enzyme-linked immunosorbent assay. Western blot analysis was applied for C9 semiquantification. Immunohistochemistry was used to detect complement C3d, C5a, C9, and myeloperoxidase.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Results<\/jats:italic>\n            \u2014Perihematomal brain edema was reduced by systemic complement depletion at 24 hours (78.8\u00b10.6% versus 81.5\u00b10.8% in control,\n            <jats:italic>P<\/jats:italic>\n            &lt;0.01) and 72 hours (81.5\u00b11.5% versus 83.6\u00b10.9% in control,\n            <jats:italic>P<\/jats:italic>\n            &lt;0.05), while cerebellar water content was unaffected (78.2\u00b10.3% versus 78.0\u00b10.1%). Complement depletion reduced TNF-\u03b1 production 2 hours after ICH. Immunocytochemistry showed that complement depletion significantly reduced perihematomal C9 deposition, C3d production, and the number of C5a- and myeloperoxidase-positive cells.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Conclusions<\/jats:italic>\n            \u2014Complement depletion by CVF attenuates brain edema in ICH, indicating that complement activation plays an important role in ICH-induced brain edema. Preventing complement activation may be effective in the treatment of ICH.\n          <\/jats:p>","DOI":"10.1161\/01.str.32.1.162","type":"journal-article","created":{"date-parts":[[2011,6,17]],"date-time":"2011-06-17T20:08:03Z","timestamp":1308341283000},"page":"162-167","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":104,"title":["Systemic Complement Depletion Diminishes Perihematomal Brain Edema in Rats"],"prefix":"10.1161","volume":"32","author":[{"given":"Guohua","family":"Xi","sequence":"first","affiliation":[{"name":"From the Departments of Surgery (Neurosurgery) (G.X., Y.H., R.F.K., J.T.H.), Physiology (R.F.K.), and Emergency Medicine (J.G.Y.), University of Michigan, Ann Arbor."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya","family":"Hua","sequence":"additional","affiliation":[{"name":"From the Departments of Surgery (Neurosurgery) (G.X., Y.H., R.F.K., J.T.H.), Physiology (R.F.K.), and Emergency Medicine (J.G.Y.), University of Michigan, Ann Arbor."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard F.","family":"Keep","sequence":"additional","affiliation":[{"name":"From the Departments of Surgery (Neurosurgery) (G.X., Y.H., R.F.K., J.T.H.), Physiology (R.F.K.), and Emergency Medicine (J.G.Y.), University of Michigan, Ann Arbor."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John G.","family":"Younger","sequence":"additional","affiliation":[{"name":"From the Departments of Surgery (Neurosurgery) (G.X., Y.H., R.F.K., J.T.H.), Physiology (R.F.K.), and Emergency Medicine (J.G.Y.), University of Michigan, Ann Arbor."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian T.","family":"Hoff","sequence":"additional","affiliation":[{"name":"From the Departments of Surgery (Neurosurgery) (G.X., Y.H., R.F.K., J.T.H.), Physiology (R.F.K.), and Emergency Medicine (J.G.Y.), University of Michigan, Ann Arbor."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"crossref","unstructured":"Kase CS Caplan LR. Intracerebral Hemorrhage. Boston Mass: Butterworth-Heinemann; 1994.>","DOI":"10.1016\/B978-0-7506-9308-0.50012-9"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.3171\/jns.1998.89.6.0991"},{"key":"e_1_3_2_3_2","unstructured":"Hua Y Xi G Keep RF Xiang J Hoff JT. Complement C9 accumulation membrane attack complex (MAC) formation and clusterin upregulation following intracerebral hemorrhage. J Cereb Blood Flow Metab. 1999;19(suppl 1):S670. Abstract."},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.3171\/jns.2000.92.6.1016"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0162-3109(97)00059-3"},{"key":"e_1_3_2_6_2","doi-asserted-by":"crossref","first-page":"5477","DOI":"10.4049\/jimmunol.152.11.5477","volume":"152","year":"1994","unstructured":"Piddlesden SJ, Storch MK, Hibbs M, Freeman AM, Lassmann H, Morgan BP. Soluble recombinant complement receptor 1 inhibits inflammation and demyelination in antibody-mediated demyelinating experimental allergic encephalomyelitis. J Immunol. 1994;152:5477\u20135484.","journal-title":"J Immunol"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.1995.107"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5427.595"},{"key":"e_1_3_2_9_2","first-page":"12775","volume":"91","year":"1994","unstructured":"Fritzinger DC, Bredehorst R, Vogel CW. Molecular cloning and derived primary structure of cobra venom factor. Proc Natl Acad Sci U S A. 1994;91:12775\u201312779.","journal-title":"A"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1097\/00006123-199607000-00028"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0361-9230(97)00408-5"},{"key":"e_1_3_2_12_2","first-page":"245","volume":"83","year":"1991","unstructured":"Piddlesden S, Lassmann H, Laffafian I, Morgan BP, Linington C. Antibody-mediated demyelination in experimental allergic encephalomyelitis is independent of complement membrane attack complex formation. Clin Exp Immunol. 1991;83:245\u2013250.","journal-title":"Clin Exp Immunol"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-17-06713.1998"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004010050801"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/str.30.6.1247"},{"key":"e_1_3_2_16_2","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.4049\/jimmunol.158.4.1857","volume":"158","year":"1997","unstructured":"Mulligan MS, Schmid E, Till GO, Hugli TE, Friedl HP, Roth RA, Ward PA. C5a-dependent up-regulation in vivo of lung vascular P-selectin. J Immunol. 1997;158:1857\u20131861.","journal-title":"J Immunol"},{"key":"e_1_3_2_17_2","doi-asserted-by":"crossref","first-page":"944","DOI":"10.4049\/jimmunol.103.5.944","volume":"103","year":"1969","unstructured":"Ballow M, Cochrane CG. Two anticomplementary factors in cobra venom: hemolysis of guinea pig erythrocytes by one of them. J Immunol. 1969;103:944\u2013952.","journal-title":"J Immunol"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0046-8177(83)80119-1"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.3171\/jns.1996.85.3.0468"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/str.29.12.2580"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.3171\/jns.1996.84.1.0091"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01420301"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(00)00971-X"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.168.1.443"},{"key":"e_1_3_2_25_2","doi-asserted-by":"crossref","first-page":"3455","DOI":"10.4049\/jimmunol.156.9.3455","volume":"156","year":"1996","unstructured":"Takabayashi T, Vannier E, Clark BD, Margolis NH, Dinarello CA, Burke JF, Gelfand JA. A new biologic role for C3a and C3a desArg: regulation of TNF-alpha and IL-1 beta synthesis. J Immunol. 1996;156:3455\u20133460.","journal-title":"J Immunol"},{"key":"e_1_3_2_26_2","doi-asserted-by":"crossref","unstructured":"Lucchesi BR. Complement activation neutrophils and oxygen radicals in reperfusion injury. Stroke. 1993;24(suppl I):I-41\u2013I-47.","DOI":"10.1016\/0022-2828(92)90127-L"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118818"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(00)02427-6"},{"key":"e_1_3_2_29_2","first-page":"31","volume":"150","year":"1997","unstructured":"Gasque P, Singhrao SK, Neal JW, Gotze O, Morgan BP. Expression of the receptor for complement C5a (CD88) is up-regulated on reactive astrocytes, microglia, and endothelial cells in the inflamed human central nervous system. Am J Pathol. 1997;150:31\u201341.","journal-title":"Am J Pathol"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.3109\/00207459408986002"},{"key":"e_1_3_2_31_2","doi-asserted-by":"crossref","unstructured":"Farkas I Baranyi L Okada N Liposits Z Okada H. A complement C5a fragment peptide causes apoptosis in TGW neuroblastoma cells. Neurobiol Aging. 1996;17(suppl 4):S183. Abstract.","DOI":"10.1016\/S0197-4580(96)80738-X"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-199908000-00001"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/1043-4666(92)90072-Y"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1161\/str.27.12.2312"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1161\/str.28.6.1233"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(95)01089-0"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65405-3"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.3171\/jns.1989.71.5.0718"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.1997.0573"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1159\/000028274"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.3171\/jns.1995.83.6.1045"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.3171\/jns.1997.86.2.0272"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1089\/neu.1993.10.167"},{"key":"e_1_3_2_44_2","first-page":"141","volume":"74","year":"2000","unstructured":"Mannel DN, Echtenacher B. TNF in the inflammatory response. Chem Immunol. 2000;74:141\u2013161.","journal-title":"Chem Immunol"}],"container-title":["Stroke"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/01.STR.32.1.162","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T22:16:40Z","timestamp":1715552200000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/01.STR.32.1.162"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,1]]},"references-count":44,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2001,1]]}},"alternative-id":["10.1161\/01.STR.32.1.162"],"URL":"https:\/\/doi.org\/10.1161\/01.str.32.1.162","relation":{},"ISSN":["0039-2499","1524-4628"],"issn-type":[{"value":"0039-2499","type":"print"},{"value":"1524-4628","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,1]]},"assertion":[{"value":"2000-07-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2001-01-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}