3 C3

1 3 5 5 13 19 21 21 21 25 29 33 34 41 42 43

-1-3(C3) C3 C3 2003 8 2004 10 168 24 43 Scandinavian Stroke Scale,SSS 72 2 C3 CT 3 7 Logistic C3 C3 1.21 0.23g/L 1.04 0.22g/L P<0.001 68 40.48% 72 C3 1.28 0.20 1.16 0.25 P=0.000 C3 P=0.001 C3 C CRP C-reactive Protein

-2- SSS Logistic C3 1.0g/L [OR] 10.93 95% [95%C.I] 2.37~50.41 P=0.002 1.0mmol/L OR 1.14 95%C.I 1.02~1.27 P=0.026 C3 OR 7.247 95%C.I 1.52~36.39 P=0.013 C3 C3 ( ) C3 C3 3

-3- Early Deterioration of Cerebral Infarction and Serum C3 Abstract Objective:Stroke progression is the leading cause of mortality and disability in patients with ischemic stroke.complement C3 is one of the acute phase proteins.elevated C3 is associated with traditional risk factors and the risk of ischemic events.the objective of the present study was to investigate the relationship between acute ischemic progressing stroke(ps) and serum C3. Method:One hundred and sixty-eight consecutive patients with acute cerebral infarction within the first 24 hours from onset were recruited,43 persons with non-neurological diseases as controls. PS was diagnosed when the Scandinavian Stroke Scale (SSS) score decreased two or more points between admission and 72 hours after.fasting venous blood sample was drawn on the morning of the second day after admission.c3 and other clinical chemistry variables were measured in fresh serum.cranial CT was performed on admission and repeated on days 3 to 7 of hospitalization.these variables which were significantly associated with progressing stroke in univariate analysis were included in Logistic regression analysis as confounders to investigate the relationship between PS and C3. Result: Level of serum C3 were higher in patients with cerebral infarction than in controls(1.21 0.23g/L versus 1.04 0.22g/L P<0.001). Sixty-eight (40.48%) patients had PS.Level of serum C3 were higher in patients with PS than in those with non-ps (1.28 0.20 versus 1.16 0.25,P=0.000).A higher C3 were accompanied a higher tendency of prevalence of PS (P=0.001).C3 was significantly correlated with such variables which were significantly associated with PS in univariate analysis as blood

-4- glucose,cholesterol, low density lipoprotein,count of neutrophil,count of eosins,value of CRP after logarithmic transformation and SSS on addmission.in mutiple Logistic regression analysis,c3 (OR [Odds Ratio] for each 1.0g/L rise:10.93;95% C.I [confidence interval] 2.37~50.41;p=0.002)and high blood glucose (OR for each 1.0mmol/L rise:1.14 95%C.I:1.02~1.27;P=0.026) were the independent risk factors for PS.When further adjusted with infarction volume,c3 was still included in the regression model,blood glucose was substituted by infarction volume and diabetes mellitus. Conclusion: Here we first report the relationship between the level of serum C3 and PS.Independent of blood glucose,diabetes mellitus and infarction volume, elevated serum C3 maybe a important prognostic factor for PS. A higher C3 were accompanied a higher tendency of prevalence of PS. Elevation of C3 may be related to a few pathophysiological mechanisms in ischemic stroke. Key words: Ischemic stroke;stroke outcome;c3-complement;prognostic factor

-5-80% (progressing stroke,ps) 26% 43% [1 2] [3] EPSS 72 40% 8% 3 BI[barthel index]<15 77% 30% [2] [4] IL-6 TNF-a [25 29] [6] C3 C4 [7] C3 C4 C3 C3 C4mRNA [8] C3 [9] C3

-6- ECASS-1 [10] 24 MRS Modified Rankin Scale 0 1 9.7% 46.4% 3 31.2% 11.5% p<0.0001 24 90 21.6% 6.4% MRS >1 91.7% 56.3% EPSS 72 40% 8% 3 BI[barthel index]<15 77% 30% Baber [11] OCSP (Scandinavian Stroke Scale,SSS) 30 70% 55% p=0.002 [3] Stroke Progression SP Deteriorating Stroke Evolving Stroke [1] 48 72 [1] D valos [10] 24

-7- early progressing stroke EPS 24 1 late progressing stroke LPS 6 2 [12] 6 6 CSS 1 SSS 2 2 [1] 26% 43% 37% 33% 7% [13] 72 Caplan [30] 1 2 3

-8-1 Danalos 1990 [14] 1999 [10] 231 24 Jorgensen Barber [11 15] Jorgensen [15] 36 Barber [11] 1.01( 1mmHg) Christensen [16] [17] 326 108 25 Logistic

-9-2 Toni [1,69] 24 Christensen [16] Barber [11] Christensen [16] 72 24 [18] [19] dysarthria-clumsy hand syndrome 3 D valos [10] CT 24 1 Arenillas [20] MRI DWI 89cm 3 85.7% 95.7% 6 TCD MCA TCD [21]

-10-4 Gastillo [22] 43 85 200umol/L 8.2umol/L 90% Serena [23] 113 27 23.9% - * / - GABA (253±70 123±73 mmol/l) GABA (1406±63 4116±97 nmol/l) ( P<0.001) >200 mmol/l GABA <240nmol/L 67% 84% >106 85% 5 Baber [24] 24 VIIc,VIIIc,IXc, 1+2[F1+2], - TAT,D, von Willebrand factor vwf tissue plasminogen activator 219 54 F1+2(1.28 1.06nmol/L,P=0.01),TAT(5.28 4.07microg/L,P<0.01),D- (443 194ng/mL,P<0.001) vwf(216 198IU/dL,P<0.05) logistic D- [66,69]

-11-6 -1 IL-1 TNF- -6 IL-6 Vila [25] 83 148 TNF- IL-6 IL-6>21.5pg/mL OR 37.7, IL-6>6.3pg/mL OR,13.1 92% 83% 84% 81% TNF- Castellanos TNF- >14pg/mL OR 511 3.0 ICAM 208pg/mL OR 315 4.2 [29] Vila [26] IL-10 IL-4 IL-10<6pg/mL 3.1 IL-4 7 NO NO NO CNOS Ca/CaM NO NOS inos NO 1-2 inos NO NO NO

-12- Gastillo [27] 24 NO NO-m NO-m>5umol/L 8 Dalavos [28] 45 55 24 >275 ng/ml(or,33.5;95%ci,4.7~235) >11ng/mL(OR,11.4;95%CI,3.1~41) 9 Roden-Jullig [4] 72 48 325mg/ 220 221 15.9% 16.7% ECASS [10] 615 r-tpa 1.1mg/Kg 6 r-tpa 119 38% 112 37% [79]

-13- Baber [11] 196 6 3% 16 8% Logistic [31 32 33] [6 34] [35] [36,37], 30 1 C1q C1r C1s C2 C3 C4 C5 C6 C7 C8 C9 C1qrs-C4-C2-C3-C5-C6-C7-C8-C9 2 B D P C3 C3Nef C3 C5 C9 C3-B-C5-C6-C7-C8-C9 C3 B C3bBb C3 P C3 C3 C5

-14-3 mannose binding lectin MBL Mannose Association Serum Protease,MASP C4 C2 C3 C5-C9 MBL C1q MASP-1 MASP-2 C1r C1s [65] MBL MASP-1 MASP-2 MASP-1 MASP-2 C1r C1s MASP-1 C3 C2 MASP-2 C4 C2 C5 C9 MBL C3 3 C5 C9 MAC 1 1 [65]