[1] SALOMON J A, WANG H D, FREEMAN MK, et al.Healthy life expectancy for 187 countries, 1990-2010:A systematic analysis for the Global Burden DiseaseStudy 2010 [J]. The Lancet, 2012, 380(9859): 2144-2162.
[2] KIM A S, CAHILL E, CHENG N T. Global strokebelt: Geographic variation in stroke burden worldwide[J]. Stroke, 2015, 46(12): 3564-3570.
[3] STEGMAYR B, ASPLUND K. Diabetes as a risk factorfor stroke: A population perspective [J]. Diabetologia,1995, 38(9): 1061-1068.
[4] CAPES S E, HUNT D, MALMBERG K, et al. Stresshyperglycemia and prognosis of stroke in nondiabeticand diabetic patients: A systematic overview [J].Stroke, 2001, 32(10): 2426-2432.
[5] ERGUL A, KELLY-COBBS A, ABDALLA M, et al.Cerebrovascular complications of diabetes: focus onstroke [J]. Endocrine, Metabolic & Immune Disorders-Drug Targets, 2012, 12(2): 148-158.
[6] PULSINELLIWA, LEVY D E, SIGSBEE B, et al. Increaseddamage after ischemic stroke in patients withhyperglycemia with or without established diabetesmellitus [J]. The American Journal of Medicine, 1983,74(4): 540-544.
[7] PUTAALA J, LIEBKIND R, GORDIN D, et al. Diabetesmellitus and ischemic stroke in the young: Clinicalfeatures and long-term prognosis [J]. Neurology,2011, 76(21): 1831-1837.
[8] ERGUL A, ELGEBALY M M, MIDDLEMORE M L,et al. Increased hemorrhagic transformation and alteredinfarct size and localization after experimentalstroke in a rat model type 2 diabetes [J]. BMC Neurology,2007, 7: 33.
[9] AIR E L, KISSELA B M. Diabetes, the metabolic syndrome,and ischemic stroke: Epidemiology and possiblemechanisms [J]. Diabetes Care, 2007, 30(12): 3131-3140.
[10] MART′IN A, ROJAS S, CHAMORRO A, et al. Whydoes acute hyperglycemia worsen the outcome of transientfocal cerebral ischemia? Role of corticosteroids,inflammation, and protein O-glycosylation [J]. Stroke,2006, 37: 1288-1295.
[11] KRUYT N D, BIESSELS G J, DEVRIES J H, et al.Hyperglycemia in acute ischemic stroke: Pathophysiologyand clinical management [J]. Nature Reviews Neurology,2010, 6(3): 145-155.
[12] MASUMOTO A, MOHRI M, SHIMOKAWA H, et al.Suppression of coronary artery spasm by the Rhokinaseinhibitor fasudil in patients with vasospasticangina [J]. Circulation, 2002, 105(13): 1545-1547.
[13] OKAMURA N, SAITO M, MORI A, et al. Vasodilatoreffects of fasudil, a Rho-kinase inhibitor, on retinalarterioles in stroke-prone spontaneously hypertensiverats [J]. Journal of Ocular Pharmacology and Therapeutics,2007, 23(3): 207-212.
[14] MIYATA K, SHIMOKAWA H, KANDABASHI T, etal. Rho-kinase is involved in macrophage-mediated formationof coronary vascular lesions in pigs in vivo[J]. Arteriosclerosis, Thrombosis, and Vascular Biology,2000, 20(11): 2351-2358.
[15] GOJO A, UTSUNOMIYA K, TANIGUCHI K, etal. The Rho-kinase inhibitor, fasudil, attenuates diabeticnephropathy in streptozotocin-induced diabeticrats [J]. European Journal of Pharmacology, 2007,568(1/2/3): 242-247.
[16] LIN G R, CRAIG G P, ZHANG L L, et al. Acute inhibitionof Rho-kinase improves cardiac contractile functionin streptozotocin-diabetic rats [J]. CardiovascularResearch, 2007, 75(1): 51-58.
[17] KAWAMURA H, YOKOTE K, ASAUMI S, et al. Highglucose-induced upregulation of osteopontin is mediatedvia Rho/Rho kinase pathway in cultured rat aorticsmooth muscle cells [J]. Arteriosclerosis, Thrombosis,and Vascular Biology, 2004, 24(2): 276-281.
[18] REINIGER N, LAU K, MCCALLA D, et al. Deletionof the receptor for advanced glycation end productsreduces glomerulosclerosis and preserves renal functionin the diabetic OVE26 mouse [J]. Diabetes, 2010,59(8): 2043-2054.
[19] ZHANG Y, PENG F F, GAO B, et al. Mechanicalstrain-induced RhoA activation requires NADPHoxidase-mediated ROS generation in caveolae [J]. Antioxidants& Redox Signaling, 2010, 13(7): 959-973.
[20] GALLE J. Oxidized LDL and its compound lysophosphatidylcholinepotentiate AngII-induced vasoconstrictionby stimulation of RhoA [J]. Journal of theAmerican Society of Nephrology, 2003, 14(6): 1471-1479.
[21] CHRISSOBOLIS S, SOBEY C G. Recent evidence foran involvement of Rho-kinase in cerebral vascular disease[J]. Stroke, 2006, 37(8): 2174-2180.
[22] DIDION S P, LYNCH C M, BAUMBACH G L, etal. Impaired endothelium-dependent responses and enhancedinfluence of Rho-kinase in cerebral arterioles intype II diabetes [J]. Stroke, 2005, 36(2): 342-347.
[23] ARITA R, HATA Y, NAKAO S, et al. Rho kinaseinhibition by fasudil ameliorates diabetes-induced microvasculardamage [J]. Diabetes, 2009, 58(1): 215-226.
[24] SRIVASTAVA K, SHAO B L, BAYRAKTUTAN U.PKC-β exacerbates in vitro brain barrier damage inhyperglycemic settings via regulation of RhoA/Rhokinase/MLC2 pathway [J]. Journal of Cerebral BloodFlow & Metabolism, 2013, 33(12): 1928-1936.
[25] PEARSON J T, JENKINS M J, EDGLEY A J, et al.Acute Rho-kinase inhibition improves coronary dysfunctionin vivo, in the early diabetic microcirculation[J]. Cardiovascular Diabetology, 2013, 12: 111.
[26] SHIN H K, HUANG P L, AYATA C. Rho-kinase inhibitionimproves ischemic perfusion deficit in hyperlipidemicmice [J]. Journal of Cerebral Blood Flow &Metabolism, 2014, 34(2): 284-287.
[27] VAN NIEUW AMERONGEN G P, BECKERS C ML, ACHEKAR I D, et al. Involvement of Rho kinasein endothelial barrier maintenance [J]. Arteriosclerosis,Thrombosis, and Vascular Biology, 2007, 27(11): 2332-2339.
[28] NIZAMUDEEN Z A, CHAKRABARTI L, SOTTILEV. Exposure to the ROCK inhibitor fasudil promotesgliogenesis of neural stem cells in vitro [J]. Stem CellResearch, 2018, 28: 75-86.
[29] GUAN S J, MA Z H, WU Y L, et al. Long-termadministration of fasudil improves cardiomyopathyin streptozotocin-induced diabetic rats [J]. Food andChemical Toxicology, 2012, 50(6): 1874-1882.
[30] ALVES M G, OLIVEIRA P F, SOCORRO S, et al.Impact of diabetes in blood-testis and blood-brain barriers:Resemblances and differences [J]. Current DiabetesReviews, 2012, 8(6): 401-412.
[31] KRIJNEN P A J, SIMSEK S, NIESSEN H W M.Apoptosis in diabetes [J]. Apoptosis, 2009, 14(12):1387-1388.
[32] PRAKASH R, LI W G, QU Z, et al. Vascularizationpattern after ischemic stroke is different in control versusdiabetic rats: Relevance to stroke recovery [J].Stroke, 2013, 44(10): 2875-2882.
[33] MU Z H, JIANG Z, LIN X J, et al. Vessel dilationattenuates endothelial dysfunction following middlecerebral artery occlusion in hyperglycemic rats [J].CNS Neuroscience & Therapeutics, 2016, 22(4): 316-324.
[34] YAN T, CHOPP M, CHEN J L. Experimental animalmodels and inflammatory cellular changes in cerebralischemic and hemorrhagic stroke [J]. Neuroscience Bulletin,2015, 31(6): 717-734.
[35] LIUY, TANGGH, SUNYH, et al.The protective roleof Tongxinluo on blood-brain barrier after ischemiareperfusion brain injury [J]. Journal of Ethnopharmacology,2013, 148(2): 632-639.
[36] ZHANG Y Q,WU S J. Effects of fasudil on pulmonaryhypertension in clinical practice [J]. Pulmonary Pharmacology& Therapeutics, 2017, 46: 54-63.
[37] HUANG J, LI Y N, TANG Y H, et al. CXCR4 antagonistAMD3100 protects blood-brain barrier integrityand reduces inflammatory response after focal ischemiain mice [J]. Stroke, 2013, 44(1): 190-197.
[38] GASCHE Y, COPIN J C, CHAN P H. The role ofmetalloproteinases on blood-brain barrier breakdownafter ischemic stroke [M]//FEUERSTEIN G Z. Inlammationand stroke. Basel, Switzerland: Birkh¨auserBasel, 2001: 265-274.
[39] LAZAREVIC-PASTI T, LESKOVAC A, VASIC V.Myeloperoxidase inhibitors as potential drugs [J]. CurrentDrug Metabolism, 2015, 16(3): 168-190.
[40] RAKIETEN N, RAKIETEN M L, NADKARNI M R.Studies on the diabetogenic action of streptozotocin(NSC-37917) [J]. Cancer Chemother Rep, 1963, 29:91-98.
[41] ZAKRZESKA A, GROMOTOWICZ-POPWSKA A,SZEMRAJ J, et al. Eplerenone reduces arterial thrombosisin diabetic rats [J]. Journal of the Renin-Angiotensin-Aldosterone System, 2015, 16(4): 1085-1094.
[42] DEMIRY¨UREK S, KARA A F, C?ELIK A, et al. Effectsof fasudil, a Rho-kinase inhibitor, on myocardialpreconditioning in anesthetized rats [J]. EuropeanJournal of Pharmacology, 2005, 527(1/2/3): 129-140.
[43] RIKITAKE Y, KIM H H, HUANG Z H, et al. Inhibitionof Rho kinase (ROCK) leads to increased cerebralblood flow and stroke protection [J]. Stroke, 2005,36(10): 2251-2257.
[44] VENNIN C, RATH N, PAJIC M, et al. TargetingROCK activity to disrupt and prime pancreatic cancerfor chemotherapy [J]. Small GTPases, 2017: 1-8. DOI:10.1080/21541248.2017.1345712.
[45] ALLEN C, SRIVASTAVA K, BAYRAKTUTAN U.Small GTPase RhoA and its effector Rho kinase mediateoxygen glucose deprivation-evoked in vitro cerebralbarrier dysfunction [J]. Stroke, 2010, 41(9): 2056-2063.
[46] THOMPSON B J, RONALDSON P T. Drug deliveryto the ischemic brain [J]. Advances in pharmacology,2014, 71: 165-202.
[47] LATOUR L L, KANG D W, EZZEDDINE M A, et al.Early blood-brain barrier disruption in human focalbrain ischemia [J]. Annals of Neurology, 2004, 56(4):468-477.
[48] SIMPKINS A N, DIAS C, LEIGH R. Identification ofreversible disruption of the human blood-brain barrierfollowing acute ischemia [J]. Stroke, 2016, 47(9): 2405-2408.
[49] GIBSON C L, SRIVASTAVA K, SPRIGG N, et al. Inhibitionof Rho-kinase protects cerebral barrier fromischaemia-evoked injury through modulations of endothelialcell oxidative stress and tight junctions [J].Journal of Neurochemistry, 2014, 129(5): 816-826.
[50] FUJIIM, DURIS K, ALTAY O, et al. Inhibition of Rhokinase by hydroxyfasudil attenuates brain edema aftersubarachnoid hemorrhage in rats [J]. NeurochemistryInternational, 2012, 60(3): 327-333.
[51] DEJANA E. Endothelial cell-cell junctions: Happytogether [J]. Nature Reviews Molecular Cell Biology,2004, 5(4): 261-270.
[52] WISPELWEY B, LESSE A J, HANSEN E J, etal. Haemophilus influenzae lipopolysaccharide-inducedblood brain barrier permeability during experimentalmeningitis in the rat [J]. The Journal of Clinical Investigation,1988, 82(4): 1339-1346.
[53] QUAGLIARELLO V J, WISPELWEY B, LONG WJ, et al. Recombinant human interleukin-1 inducesmeningitis and blood-brain barrier injury in the rat:Characterization and comparison with tumor necrosisfactor [J]. The Journal of Clinical Investigation, 1991,87(4): 1360-1366.
[54] DELI M A, DESCAMPS L, DEHOUCK M P, et al.Exposure of tumor necrosis factor-α to luminal membraneof bovine brain capillary endothelial cells coculturedwith astrocytes induces a delayed increaseof permeability and cytoplasmic stress fiber formationof actin [J]. Journal of Neuroscience Research, 1995,41(6): 717-726.
[55] BANKS W A, KASTIN A J. The interleukins-1α, -1β,and -2 do not acutely disrupt the murine blood-brainbarrier [J]. International Journal of Immunopharmacology,1992, 14(4): 629-636.
[56] TARKOWSKI E, ROSENGREN L, BLOMSTRANDC, et al. Intrathecal release of pro- and antiinflammatorycytokines during stroke [J]. Clinical &Experimental Immunology, 1997, 110(3): 492-499.
[57] ZHANG W D, SMITH C, SHAPIRO A, et al. Increasedexpression of bioactive chemokines in humancerebromicrovascular endothelial cells and astrocytessubjected to simulated ischemia in vitro [J]. Journalof Neuroimmunology, 1999, 101(2): 148-160.
[58] HE Y, XU H S, LIANG L Q, et al. Antiinflammatoryeffect of Rho kinase blockade via inhibition of NF-κB activation in rheumatoid arthritis [J]. Arthritis &Rheumatism, 2008, 58(11): 3366-3376.
[59] THORLACIUS K, SLOTTA J E, LASCHKE M W, etal. Protective effect of fasudil, a Rho-kinase inhibitor,on chemokine expression, leukocyte recruitment, andhepatocellular apoptosis in septic liver injury [J]. Journalof Leukocyte Biology, 2006, 79(5): 923-931.
[60] CHENG T, PETRAGLIA A L, LI Z, et al. Activatedprotein C inhibits tissue plasminogen activatorinducedbrain hemorrhage [J]. Nature Medicine, 2006,12(11): 1278-1285.
[61] ZLOKOVIC B V. Remodeling after stroke [J]. NatureMedicine, 2006, 12(4): 390-391.
[62] KEMPURAJ D, THANGAVEL R, SELVAKUMAR G P, et al. Brain and peripheral atypical inflammatorymediators potentiate neuroinflammation and neurodegeneration[J]. Frontiers in Cellular Neuroscience,2017, 11: 216.